Medicine, Nursing and Health Sciences School of Biomedical Sciences Annual Report 2011 Australia n Malaysia n South Africa n Italy n India www.med.monash.edu/sobs Contents 3 From the Head of School 4 Year in Review: Research 5 Year in Review: Awards 8 Year in Review: Events 10Overview 12Cancer 20 Cardiovascular Disease 26 Developmental Biology 36 Drug Design 40Immunology School of Biomedical Sciences Annual Report 2011 Editor Vicki Burkitt Design, photography and production 44 Immunology and Stem Cells 50 Infectious Diseases 60 Medical Imaging and Radiation Sciences 62Neuroscience 70Obesity MNHS Multimedia Services 76 Structural Biology Communications contacts 86 Facilities and Centres 94 Grants and Funding Telephone:+61 3 9902 9407 Email: vicki.burkitt@monash.edu Web: www.med.monash.edu/sobs Mail School of Biomedical Sciences Building 77 Monash University Clayton, Victoria 3800 Australia Cover image: Lipid droplets containing fat (red) in an adipocyte (fat cell). The protein adipose triglyceride lipase (green), which breaks down fat, is also shown. Image: Joanne Pagon. 100Education 108 Postgraduate Research 112Administration 116 Research Publications 129 Research Staff Index From the Head of School I congratulate all members of the School of Biomedical Sciences for another successful year in 2011. Researchers in the School were awarded $49 million of research income from national and international funding sources, and our scientists published 484 publications, 38 in high impact journals, including: Nature, Nature Biotechnology, Cancer Cell, Nature Immunology, Immunity and Nature Methods. Professor Christina Mitchell Professor Jamie Rossjohn had a stellar year. He was awarded a 2011 NHMRC Australia Fellowship and will receive $4 million over five years to further his immunity research. He was also a joint recipient of the prestigious Roche Organ Transplantation Research Foundation Recognition Prize. Professor Rob Pike has relinquished his role as Head of Biochemistry and Molecular Biology, and I thank him for his outstanding contribution over the last five years. He will be replaced by Professor Rod Devenish in an acting capacity until a new Head is appointed. Associate Professor Martin Lackmann’s cancer research project made the NHMRC top 10 grants for 2010. After his longstanding work on the role of Eph receptors in cancer, a candidate drug is now being tested for safety and anti-tumour effects in leukaemia patients in hospitals in Australia and the US. Congratulations go to Professor Wayne Hodgson, who is the Faculty’s new Deputy Dean (Education). He has therefore stepped down from his role as co-Head of Pharmacology. Professor Michael Cowley, Director of the Monash Obesity and Diabetes Institute, added another accolade to his list. The obesity researcher was elected a Fellow of the Australian Academy of Technological Sciences and Engineering. Structural biology infrastructure at Monash will be boosted by the establishment of The Clive and Vera Ramaciotti Centre for Structural Cryo-Electron Microscopy. A group led by Professors James Whisstock and Ian Smith, and including scientists from Walter and Eliza Hall Institute, the University of Melbourne, La Trobe University, Burnet Institute and Peter MacCallum Cancer Centre, received $1 million from Ramaciotti Foundations and $640,000 from the Australian Research Council. The School continues to promote excellence in its teaching programs. Highlights for the year include Dr Richard Loiacono receiving the Dean’s Award for Excellence in Education (Quality) and the introduction of Biomedical Science Scholars and Biomedical Science Advanced Honours programs. In these programs, high-achieving students are matched with academic mentors within the School and attend research platform tours and seminars. We welcomed many new staff to the School: in particular, Professor Christian Doerig, malaria researcher and our new Head of Microbiology; former Governor of Victoria, Professor David de Kretser, who continues his research on fertility; obesity researchers Professors David Spanswick and Mark Sleeman; neurodegenerative disease researcher Professor Zhi-Cheng Xiao; and Dr Jose Polo, a stem cell scientist. On a personal note, in October 2011 I took up the role of Dean of Medicine, Nursing and Health Sciences after a five-year term as Head of School. I am pleased to announce that following a comprehensive recruitment process Professor John Carroll from University College London has been appointed as my replacement. John is an eminent scientist and leader who will bring a wealth of experience to the School. The Deputy Head of School Professor Phillip Bird will act as Head until John joins us in September 2012. I thank the School’s Executive team including the Department Heads for their continuing support and leadership. I am particularly grateful to the School Manager Doug McGregor and his team, who keep the School functioning at a high level. I also wish to thank staff in the HR and finance service hubs for their work in 2011. Finally, I gratefully acknowledge the contribution of colleagues in the Monash senior leadership group: particularly, former Dean of Medicine Professor Steve Wesselingh, Deputy Vice-Chancellor (Research) Professor Edwina Cornish, Deputy Vice-Chancellor (Education) Adam Shoemaker, and Vice-Chancellor Professor Ed Byrne. Professor Christina Mitchell Dean, Medicine, Nursing and Health Sciences Professor John Davies stepped down as Head of Microbiology in preparation for retirement in 2013. As Head of Department and former Deputy Head of School he has provided significant and longstanding service for which we are all grateful. 3 Annual Report 2011 Year in Review Year in Review: Awards Year in Review: Research Unravelling the natural killer within us Making heart cells from stem cells A team of scientists co-led by Professor Jamie Rossjohn (Monash University) and Associate Professor Andrew Brooks (University of Melbourne) has provided detailed structural insight of how an innate immune cell receptor called KIR3DL binds to its ligand HLA-B57. The KIR family of proteins are produced by natural killer cells, which remove tumours and virus-infected cells, including HIV. These findings, by J. Vivian et al., represent the first study to determine the molecular basis of KIR3DL1 recognition (Nature, 2011. Oct 23; 479 (7373): 401-405). Professors Ed Stanley and Andrew Elefanty, together with national and international collaborators, have successfully and reliably generated human heart muscle cells from genetically modified human embryonic stem cells expressing a fluorescent marker under the control of the important cardiac gene NKX2-5. They have also used these cells to identify new cardiac cell surface proteins. These findings will allow researchers to use drug screening and tissue engineering strategies to develop candidate treatments for heart disease (Nature Methods, 2011. 8(12): 1037-1040. Nature Biotechnology, 2011. 29(11): 1011-1018). Recognition of ß–linked self glycolipids mediated by natural killer T cell activation A team of scientists co-led by Professor Jamie Rossjohn (Monash University), Professor Dale Godfrey (University of Melbourne) and Associate Professor Laurent Gapin (National Jewish Health and University of Colorado School of Medicine) has shown how Natural killer T (NKT) cells recognise self-antigens is similar to how microbial molecules are recognised. Here they suggest a mechanism for NKT autoimmunity, where selfantigens are processed to resemble the conformation of foreign microbial antigens. NKT cells are linked to microbial immunity, autoimmunity, allergy and cancer, and represent an important immunotherapeutic target with clinical potential (Nature Immunology, 2011. Jul 31; 12(9): 827-833). 4 Structure of KIR3DL1 (magenta) in complex with HLA-B*57:01. The HLA heavy chain is coloured green, the light chain is cyan, and the peptide presented by the HLA is orange. Metabolic proteins and obesity An international team of scientists, led by Professor Tony Tiganis, has established for the first time how protein tyrosine phosphatase, or TCPTP, regulates the hormone leptin, which plays a key role in body weight maintenance and reproductive health. They have also shown that increased levels of TCTP in the brain region called the hypothalamus results in leptin resistance and morbid obesity. These findings help explain how obesity progresses, providing clues for future treatments (Cell Metabolism, 2011. Nov 2; 14(5): 684-699). Cryo-electron microscopy centre for Victoria Immunity and transplantation research recognised Victorian scientists are one step closer to having a dedicated structural cryo-electron microscopy facility, with $1 million committed by Ramaciotti Foundations and $640,000 from the Australian Research Council. The Clive and Vera Ramaciotti Centre for Structural Cryo-Electron Microscopy, which will be built at Monash University, will help scientists answer difficult structural biology questions. The centre, to be led by Professors James Whisstock and Ian Smith (School of Biomedical Sciences), and Associate Professor Mike Lawrence (Walter and Eliza Hall Institute), will also include collaborators from the University of Melbourne, La Trobe University, Burnet Institute and Peter MacCallum Cancer Centre. Professor Rossjohn, from the Department of Biochemistry and Molecular Biology, was awarded a 2011 NHMRC Australia Fellowship. He will receive $4.0 million of funding over five years to further his research in immunity. Also, Professor Rossjohn and Dr James McCluskey, from the University of Melbourne, are joint recipients of the Roche Organ Transplantation Research Foundation Recognition Prize. Professor Rossjohn received a plaque at a ceremony in Philadelphia on 30 April. The two scientists had previously been awarded a ROTRF research grant worth $300,000 Swiss Francs over three years. Obesity expert an Australian academy fellow Associate Professor’s Martin Lackmann’s cancer research project was named one of the ten best research projects in 2010 by NHMRC. The scientist from the Department of Biochemistry and Molecular Biology studies Eph receptors, proteins that play a critical role in the assembly of healthy tissues and organs, and tumours. He has developed an antibody called KB004 that recognises a specific Eph receptor on the surface of leukaemic cells and on cells lining tumour blood vessels. This candidate drug is being tested for safety and anti-tumour effects in leukaemia patients in hospitals in Australia and the US. Professor Michael Cowley, from the Department of Physiology and Director of the Monash Obesity and Diabetes Institute, was elected a Fellow of the Australian Academy of Technological Sciences and Engineering. Professor Cowley joins other technology and research leaders at Monash, including: Dr Alan Finkel AM, Chancellor; Professor Edwina Cornish, Senior Deputy Vice-Chancellor and DVC (Research); and Professor Rod Hill, Pro-Vice Chancellor (Industry Engagement and Commercialisation). Cancer research project makes top ten Green fluorescent protein expression in contracting human heart muscle cells grown from genetically modified human embryonic stem cells. Ramaciotti Biomedical Research awardees with Perpetual and Ramaciotti Foundation representatives. Image: Nic Long. 2011 NHMRC Australia Fellow, Professor Jamie Rossjohn (right) with The Hon Mark Butler MP. Image: NHMRC. PTP1B and TCPTP decrease leptin signalling in obesity. Professor Michael Cowley (right) receives his Fellowship certificate from Professor Robin Batterham, ATSE President. Image: ATSE. Associate Professor Martin Lackmann (left) with The Hon Mark Butler MP. Image: NHMRC. 5 Annual Report 2011 Year in Review Year in Review: Awards Infectious diseases award for Monash physician and researcher When images take centre stage Reproductive biologists in the spotlight Dr Ian Smyth, from the Departments of Anatomy and Developmental Biology, and Biochemistry and Molecular Biology, and Dr Kieran Short, from the Department of Biochemistry and Molecular Biology, both won 2011 Wellcome Trust image awards for their stunning medical images. They each received £200 and a trophy. Also, Dr Ian Smyth was third-placed in the 2011 New Scientist Eureka Prize for science photography. He received $2000 prize money for his digital image showing how the fetal lung of a mouse branches to form airways. Professors Iain Clarke, Head of the Department of Physiology, and Moira O’Bryan, from the Department of Anatomy and Developmental Biology, were appointed fellows of the Society for Reproductive Biology at the 2011 Annual Society for Reproductive Biology meeting, in Cairns. Also at the same conference, Dr Jeremy Smith, from the Department of Physiology, was the joint winner of the 2011 Newcastle Reproduction Emerging Research Leader Award, together with Associate Professor Stephen Tong from the University of Melbourne. Amgen award for stem cell research Australian Group of Eight fellowship supports international collaboration Dean’s awards for research and education Associate Professor Sharon Ricardo from the Monash Immunology and Stem Cell Laboratories received the Amgen Best Basic Science Award at the Australian and New Zealand Society of Nephrology meeting for her research on the generation of stem cells from patients with kidney disease. She received a cash prize of $3,300 to develop patient-specific stem cell lines for disease modelling and targeted drug treatments. Award finalists were selected by abstract peer review prior to the meeting and awards were judged on presentation and science by independent judging panels. Dr Branka Jelicic, from the Rudjer Boskovic Institute in Zagreb, Croatia, received an Australian Group of Eight fellowship to work with Dr Ana Traven at the Department of Biochemistry and Molecular Biology. Dr Jelicic studied how the fungal pathogen Candida albicans, which kills patients in hospitals, forms complex, highly drug-resistant structures called biofilms. During her time here, Dr Jelicic authored two manuscripts together with Dr Traven, including a paper in press in the prestigious journal PLoS Genetics. The fellowship is worth $20,000 AUSD and provides support for a six-month visit. Dr Anton Peleg, recipient of the Frank Fenner Award for Advanced Research in Infectious Diseases. Drs Ian Smyth (left) and Kieran Short with a Wellcome award-winning image. Dr Jeremy Smith (left), joint winner of the 2011 Newcastle Reproduction Emerging Research Leader Award. Image: Society for Reproductive Biology. Victoria Hewitt, Adam J. Berry Memorial Fund recipient. Associate Professor Sharon Ricardo. Dr Branka Jelicic, Australian Group of Eight University fellowship recipient. Dean’s Award winners: Dr Stephanie Gras (left) and Professor David Jans. Anthony Koelmeyer award recipients. From left to right: Jeffrey Moore, Sarah Haas Lockie and Andrew Clarke. Dr Anton Peleg received the Frank Fenner Award for Advanced Research in Infectious Diseases at the Australasian Society of Infectious Diseases Annual Scientific Meeting, in Lorne, Victoria. The physician and scientist from the Department of Microbiology was recognised for his pioneering infectious diseases research on the hospital-acquired pathogens Acinetobacter baumannii and Staphylococcus aureus, and infections in immunocompromised patients. Dr Peleg received a certificate and $5,000. He also presented a lecture. 6 Year in Review: Awards Scientists from the Department of Biochemistry and Molecular Biology received Dean’s Awards for Excellence in Research from former Dean Professor Steve Wesselingh. Dr Stephanie Gras, who studies how the T cell receptor recognises harmful viruses, received an early career award jointly with Dr Kate Hoy from the School of Psychology and Psychiatry. Professor David Jans, who studies how proteins from Dengue, rabies and respiratory syncitial viruses move into and out of the cell nucleus to evade immune responses, received a distinguished career award. Also, Dr Richard Loiacono from the Department of Pharmacology received the Dean’s Award for Excellence in Education (Quality). PhD student travels for mitochondrial research PhD student Victoria Hewitt received funding from the Australian Academy of Sciences, National Institutes of Health and the 2011 Adam J Berry Memorial Fund to spend three months in the laboratory of Dr Susan Buchanan, a leader in membrane protein crystallography at the National Institute of Diabetes and Kidney Diseases, in the US. Victoria, who conducts mitochondrial research at the Department of Biochemistry and Molecular Biology, learned new techniques in protein biochemistry and also set up a research partnership between the two laboratories. The international program was established in memory of Adam Berry, a young Australian scientist. Flying high for science Three PhD students scored inaugural Anthony Koelmeyer International PhD Excellence awards. They received $1,500 each towards conference costs and research training in overseas laboratories. Andrew Clarke, from the Department of Biochemistry and Molecular Biology, attended an immunology conference in Greece and visited labs in England, Scotland and Wales. Sarah Haas Lockie, from the Department of Physiology, attended a Society for Ingestive Behaviour meeting in Florida, and visited labs in Michigan and Ohio, US. Jeffrey Moore, from the Department of Pharmacology, attended the American Heart Association’s High Blood Pressure Research Scientific Sessions in Florida and visited colleagues at Emory University, in Atlanta. 7 Annual Report 2011 Year in Review: Events Big 5-0 for biochemistry teaching and research Past and present members of the Department of Biochemistry and Molecular Biology gathered together to celebrate 50 years at Monash University at the Melbourne Convention and Exhibition Centre. During the mini-symposium that marked this event, former Heads of Department Professors Robert Pike and Christina Mitchell spoke about the development of biochemistry here from its early beginnings to today, and Monash alumnus Professor John Mattick AO discussed the role of non-coding RNAs in the evolution and development of complex organisms. Guests included former academic and professional staff, and colleagues from other departments and institutes in Melbourne. Golden anniversary for anatomy teaching and research The Department of Anatomy and Developmental Biology also celebrated their 50th anniversary at the School of Biomedical Sciences. Current and former staff and alumni discussed directions in research and teaching during this period, as well as plans for the future. Before and after the speeches, there were opportunities for guests to tour the anatomy teaching, research and histology laboratories and mingle informally. Biochemistry anniversary guests. From left to right: Associate Professor Merrill Rowley, Dr Senga Whittingham and Dr Marie-Paule van Damme. Image: Phillip Nagley. 8 Guests mingling at the anatomy anniversary event. Public forum to raise stem cell awareness As part of Stem Cell Awareness Day, Monash Immunology and Stem Cell Laboratories hosted free public seminars at BMW Edge, at Federation Square. Research leaders discussed stem cell therapy approaches for osteoarthritis and neurological disorders, including: Multiple Sclerosis, spinal cord injury and Alzheimer’s Diseases. Guest speakers included MISCL director Professor Richard Boyd; industry partner and Mesoblast CEO Professor Silviu Itescu; stem cell researchers Professor Andrew Elefanty, Professor Ed Stanley, Professor Colin Poulton and Dr Martin Short; neurosurgeons Professor Jeff Rosenfeld and Dr Tony Goldschlager; and North Melbourne Football Club doctor, Dr Dan Bates. The end of antibiotics public lecture Among the public outreach programs for the year, the ARC Centre of Excellence in Structural and Functional Microbial Genomics organised a public lecture at BMW Edge, at Federation Square, as part of National Science Week. Dr Paul Johnson from Austin Health presented the lecture: The End of Antibiotics, a topical theme given the rise of antibiotic resistant bacteria worldwide. The lecture was followed by a panel discussion comprising staff from the Monash Department of Microbiology. Dr Martin Short speaking at Stem Cell Awareness Day. Overview: We conduct research within these departments: >> Anatomy and Developmental Biology >> Biochemistry and Molecular Biology >> Immunology Clayton >> Medical Imaging and Radiation Sciences >> Microbiology >> Monash Immunology and Stem Cell Laboratories >> Pharmacology >> Physiology We study: >> Cancer >> Cardiovascular Disease >> Developmental Biology >> Drug Design >> Immunology >> Infectious Diseases >> Medical Imaging and Radiation Sciences >> Neuroscience >> Obesity >> Stem Cells >> Structural Biology Cancer One in three men and one in four women in Australia will develop cancer by the age of 75* >> H ow do tumours develop and which proteins are involved? >> H ow do cancer-susceptible cells respond to environmental stresses? >> W hat role do stem cells play in breast and prostate cancer? >> What is the role of estrogen in prostate cancer? >> How do bacteria cause stomach cancer? >> H ow do cancer cells invade tissues and spread? >> W hat biomarkers can we use to detect early-stage colorectal cancer? >> How can we develop new treatments that target tumours and spare healthy tissues? *Cancer Australia www.canceraustralia.gov.au/affected-cancer/cancer-australia Complex arrangement of prostatic stromal cells in experimental models of prostate cancer. Image: Ms Hong Wang. 12 Annual Report 2011 Cancer Microbial Oncogenesis Laboratory Infection with the rod-shaped bacteria Helicobacter pylori results in peptic ulcers. Helicobacter pylori-infected persons have a 2- to 8-fold increased risk of developing gastric cancer compared with uninfected individuals. Our laboratory uses Helicobacter pylori infection as a model system to study how bacteria can infect target cells and cause them to become malignant. Research Fellow PhD Students We investigate the molecular mechanisms by which Helicobacter pylori 'inject' cancer-inducing proteins into stomach cells and how host receptor proteins such as integrins are co-opted by the bacteria to participate in this process. Honours Students We also hope to understand how Helicobacter pylori influence host signalling pathways during chronic inflammation and gain novel insights into how healthy tissue can become cancerous during chronic infection and inflammation. Dr Rebecca Gorrell Research Assistant Ms Jye Guan Ms Paige Everingham Mr Thai Son Nguyen Ms Mona Anoushiravani Tafreshi Mr Abolghasem Tohidpour Mr Nicholas Clark Ms Suzzane Huang Mr Samuel Palframan Dr Terry Kwok-Schuelein NHMRC Equipment Grant Faculty Strategic Grant • Structural analysis of the Helicobacter pylori virulence protein CagL for development of novel therapeutics (2011–2012). Research Fellows Dr Degu Abebe Dr Rae Farnsworth Dr Nadia Harun Dr Peter Janes Dr April Tan Dr Mary Vail Research Assistants Mr Chanly Chheang Ms Aileen Hea Ms Linda Hii Ms Carmen Llerena PhD Students • Helicobacter pylori VacA toxin: modulation of human mitochondrial function by a bacterial pathogen (2011–2015). Ms Lakmali Atapattu Ms Eva Nievergall Ms Catherine To Dr Darius Lane PhD Students Mr Po-Hua Chang Ms Samantha Fernandes Ms Megan Kerr Masters Students Ms Joannah Cane Ms Mun Joo Chuei Mr Samuel Thompson We are now developing candidate anti-cancer therapeutics that can detect and destroy tumour cells and tumour blood vessels in cancer patients. Our current drug candidate is a monoclonal antibody that recognises a specific Eph receptor on the surface of leukaemic cells and on cells lining tumour blood vessels. As this antibody attacks these cancerous cells and disrupts supporting blood vessels but not healthy tissues, this molecule is now being tested for safety and anti-tumour effects in leukaemia patients in hospitals in the US and Australia. Cancer Australia Priority-driven Collaborative Cancer Research Scheme • Preclinical and clinical evaluation of an antibody targeting prostate carcinoma, Lackmann/Scott/Boyd (2008–2011). KaloBios Pharmaceuticals Inc. Translational Research and In-licensing Agreement and Research Support • Molecular engineering of therapeutics targeting disease-modulating cell surface receptors, Lackmann/ Scott/Boyd (2010–2012). Awards and Achievements Associate Professor Martin Lackmann • Cancer research project awarded NHMRC Top Ten by the Hon Mark Butler MP, February 2011. • Treatment of first leukemia patient at the Moffit Cancer Centre (Florida, US) with an anti-cancer antibody developed in the Lackmann lab, March 2011. • Colorectal cancer-molecular basis to targeted therapeutics, Burgess/Scott/Simpson/Garrett/ Lackmann/Ernst/Ramsey/Heath/Caruso (2009–2013). Human Frontiers Science Program Organisation (Strasbourg, France) • The molecular dynamics and imaging of Eph receptorguided cell positioning in tissue assembly, Pawson/Neel/ Lackmann/Bastiaens (2009–2011). Intravital imaging of tumour vessels. Tumour vessels stained with green fluorescent dye (vessel wall) and red fluorescent quantum dots (blood), showing vessel leakiness. Image: Dr Mary Vail. Dr Alfons Lawen www.med.monash.edu.au/biochem/staff/lackmann.html Iron is important for cellular survival: without it, every cell will die. In its physiological form, extracellular iron is complexed by chelators, molecules that bind to metallic ions. Research Fellow We are interested in proteins that reside on the surface of tumour cells, and control their interaction with surrounding cells and tissues. Of particular interest in cancer are a family of proteins called Eph receptors, which play a critical role in the assembly of healthy tissues and organs and tumours. We combine molecular engineering with imaging techniques to study fluorescently-tagged cells in intact tumours, and record the activity of Eph proteins and their partners on the cell surface. Associate Professor Martin Lackmann NHMRC Program Grant Rod-shaped Helicobacter pylori (blue) interacting with gastric epithelial cells (yellow). www.med.monash.edu.au/biochem/staff/kwok-schuelein.html Plasma Membrane Electron Transport and Iron Uptake We study how tumours invade tissues by recruiting new blood vessels and supporting connective tissue. These insights help us develop reagents that may lead to new anti-cancer therapies. • Tecnai Spirit 120kV Transmission Electron Microscope (2011–2015). NHMRC Project Grants • Roles of integrin receptors and the Helicobacter pylori protein CagL in gastritis and gastric cancer (2009–2012). Protein Interaction and Cancer Research The most important iron chelators are the protein transferrin and the metabolite citrate. In order for iron from iron citrate to be taken up by a cell, it has to be first reduced from iron (III) to iron (II). For this reduction to occur, the electrons must be supplied from inside the cell. Our lab’s main interest lies in understanding how cells transport electrons across the plasma membrane. We have analysed the cellular uptake of iron from iron citrate (Fe3+-Cit) in detail, and found that vitamin C is needed to reduce iron and to take it up. Cells actively export reduced vitamin C (ascorbate, Asc) for this purpose (in astrocytes this process is regulated by neurotransmitters) and take up oxidised vitamin C (dehydroscorbic acid, DHA). The cells then reduce it back to ascorbate and release it for further iron reduction (see figure). In this way, vitamin C supplies electrons for this important reaction and the subsequent uptake of iron. Non-transferrin iron reduction and uptake are regulated by transmembrane ascorbate cycling in K562 cells. www.med.monash.edu.au/biochem/staff/lawen.html 14 15 Annual Report 2011 Cancer Intracellular Signalling and Cancer Scientific Executive Assistant Dr Jelena Becanovic Research Fellows Dr Michele Davies Dr Jennifer Dyson Dr Sandra Feeney Dr Rajendra Gurung Dr Meagan McGrath Dr Lisa Ooms Dr Parvin Rahman Dr Absorn Sriritana Cancer Council Research Fellow Dr Meredith Layton Research Assistant Ms Katherine Roan PhD Students Ms Micka Bertucci Ms Sarah Conduit Ms Colleen D’Arcy Ms Sandra Hakim Mr Jordan Kane Ms Dharini Kethesparan Ms Tina Liu Ms Parvin Rahman Ms Natalie Rynkiewicz Dr David Sheffield Mr David Vuong Mr Brendan Wilding Honours Students Mr Matthew Eramo Ms Sruti Pillai Ms Hannah Ring Professor Christina Mitchell Head of School (to September 2011) Dean (from October 2011) Our major focus is to identify and characterise novel genes and proteins that regulate cell proliferation, death, migration and invasion. ARC Discovery Project Grant We study lipid phosphatases and adaptor proteins, which inhibit signalling in the phosphoinositide 3-kinase (PI3K) pathway. These lipid phosphatases are either expressed at high or low levels in tumours, including breast, prostate and cervical cancers. Our team investigates how these lipid phosphatases regulate cancer cell growth, proliferation and/ or cell death. Cell motility and invasion are tightly regulated to prevent the spread or metastasis of cancer cells from one tissue to another. We are examining how lipid phosphatases regulate cancer metastasis. FSHD Global Research Foundation In addition, we are investigating one of the kinases in the PI3K pathway, which is mutated and activated in 20–30% of breast, colon and endometrial tumours. Understanding how mutation leads to activation will aid in the design of strategies to switch off this pathway. Cell Stress Response Laboratory We study how cells that are susceptible to cancer and neurodegenerative diseases respond to different environmental stresses. • Regulation of neurite outgrowth by an inhibitor of PI3K signalling, Mitchell (2011–2013). • Investigation into the role of FHL1, calcineurin and NFAT in reducing muscle wasting in Fascioscapulohumeral Muscular Dystrophy (2008-2011). Muscular Dystrophy Association of USA • The role of FHL1 in regulating skeletal muscle mass and regeneration in Duchenne Muscular Dystrophy, Mitchell (2008–2011). Research Fellows Mr Gavin Higgins Ms Heling Ng Awards and Achievements Professor Christina Mitchell • Appointed Monash Dean of Medicine, Nursing and Health Sciences, October 2011. NHMRC Project Grant • Mitochondria: Molecular and cellular insights into their diverse contributions to neuronal injury, Beart/Nagley (2008–2011). NHMRC Project Grants • Characterisation of a novel regulator of angiogenesis, Mitchell (2011–2013). Composite death outcomes in mammalian cells. The death outcomes may show a range of properties depending on what cells look like and what occurs biochemically to drive cells to die. After a stroke, some stressed nerve cells undergo alternative forms of cell death called programmed necrosis and autophagic death. These types of cell death differ from apoptosis, the ‘standard’ controlled death process, or unregulated necrosis that is a rapid and messy destruction of cells. www.med.monash.edu.au/biochem/staff/nagley.html • Characterisation of a novel PI3-kinase signal terminating enzyme in breast cancer, Mitchell (2011–2013). • Identification of the molecular mechanisms by which mutations in FHL1 lead to protein misfolding and skeletal muscle disease, Mitchell/McGrath (2011–2013). Clinical Biomarker Discovery and Validation • Role of the 72 kDa 5-phosphatase in human diseases, Mitchell/ Smyth/Dyson (2010–2012). • MTMR4, regulator of PtdIns(3)P, Mitchell/Nandurkar (2009–2011). We are interested in the processes that determine the fate of these stressed cells – whether they survive or die – and how we can develop strategies to prevent or treat diseases. In 2011, we studied several cellular models of neurodegenerative diseases in neuronal cells. We characterised the death responses in primary cultured neurones (as a model of stroke) subjected to a range of stresses that occur in the acutely damaged brain. We also analysed the death responses in a motor neurone-like cell line (as a model of motor neurone disease) where protein aggregation has occurred. We collaborated with Professors Phil Beart and Mal Horne at Florey Neurosciences Institute; and Dr Julie Atkin at La Trobe University. Also, as part of the ARC Centre of Excellence on Structural and Functional Microbial Genomics, we are working with Dr Ashley Mansell at Monash Institute of Medical Research to uncover the role of a novel mitochondrial protein involved in the cell’s defence against viral infection. Our group also studies the role of the Four and Half LIM (FHL) family proteins in skeletal muscle and cardiac muscle function. Mutations in these proteins cause muscle disease in humans, leading to muscle weakness. • Role of the inositol polyphosphate 4-phosphatase type 2 in human breast cancer, Mitchell/McLean (2010–2012). Professor Phillip Nagley We develop, validate and measure novel biomarkers for the early detection and surveillance of colorectal cancer (CRC), which represents almost 10 per cent of cancers worldwide and is the second highest cause of cancer-related death in Australia. INPP4B is expressed in luminal epithelial cells (brown staining) in normal human mammary tissue. Loss of INPP4B expression is a marker of an aggressive subtype of breast cancer. www.med.monash.edu.au/biochem/staff/mitchell.html Research Fellows Dr Robert Goode Dr Zon Weng Lai B. Med. Sci Student Mr Jason Phung Unfortunately, 30–50 per cent of CRC patients present with advanced metastastic disease when prognosis is poor (five year survival <10 per cent). There is therefore an urgent need to develop more reliable, sensitive and specific screening tests that detect CRC at the early stages when therapy is most likely to be effective (five year survival >90 per cent). We believe that tumour related products are shed into the faeces which therefore represents a potential source of protein biomarkers that indicate the presence of this cancer. Professor Ed Nice DIIRD Grant • Proof of concept study to establish biomarker translational development in Victoria, Nice/Simpson/ Fox/Thompson/Barlow (2009–2010). Cancer Council of New South Wales • A colorectal cancer 'Interactome' paradigm that influences patient survival, Baker/Nice (2010–2012). Using state-of-the-art mass spectrometry, we have generated a library of over 1500 colorectal cancer-related peptides present in human faeces. We are now developing and validating sensitive and specific quantitative assays to assess panels of candidate biomarkers to successfully detect and monitor colorectal disease. NHMRC Project Grants • Colorectal cancer membrane protein interactomics, Baker/Nice (2011–2013). • Quantitative proteomic analysis of faecal biomarkers for colon cancer, Nice (2010–2012). NHMRC Development Grant • Blood based diagnostic assay for colorectal cancer, Cosgrove/Nice/LaPointe/Gibbs/McMurrick/Ruszkiewicz/ Adams/Lockett (2011–2012). 16 Protein biomarker identification and quantitation by Multiple Reaction Monitoring (MRM). In shotgun proteomics the total protein mixture is digested and analysed by LC MS/MS to identify as many proteins as possible (left panel). In MRM a known precursor mass is selected and only the signature fragmentation (MS/MS) ions selected for analysis (right panel). This approach reduces both signal complexity and time for clinical samples to be analysed. Ang and Nice, Biomedical Chromatography, 2011. 25: 82-99. 17 Annual Report 2011 Cancer Dr John Price Cancer Biology and Metastasis Laboratory The major cause of death among cancer patients is the spread of cancer from its primary site of growth to distant organs – a process called metastasis. Our primary goal is to increase our understanding of metastasis and to identify more effective treatments for advanced cancers. Research Fellows Dr Michelle Kouspou Dr Reece Lim Research Assistant Mrs Jessica Vieusseux PhD Students Mr Ryan Chai Mr Benjamin Lang Miss Chau Nguyen Currently, there are no effective treatments that combat the spread of cancer. To better understand this process, we use cell lines and mouse models to identify genes that associate positively or negatively with metastasis. We have identified a group of genes that can predict which patients will develop metastasised tumours. Many of these genes are controlled by a molecule called Heat Shock Factor-1, which we have shown is involved in cancer cell migration, growth, survival and breast cancer metastasis. We are currently screening for compounds that inhibit this molecule in cancer cells to determine if this is an effective antimetastatic treatment approach. NHMRC Project Grants • Insulin-like growth factor binding protein-2 in cancer cells, Werther/Russo/Price/Newgreen (2011–2013). • Heat shock transcription factors in bone remodelling and disease, Price/ Quinn/Benjamin (2010–2012). The Cancer Council of Victoria Grant-in-Aid • Role of Heat Shock Factor 1 in breast cancer metastasis, Price/Hunter/Wilce (2009–2011). Research Fellows Dr Reidun Aesoey Dr Preetika Balanathan Dr Kara Britt Dr Stuart Ellem Dr Luc Furic Dr Mitchell Lawrence Dr Renea Taylor Clinical Research Fellows Dr Antonio de Sousa Dr Paul Manohar Dr David Pook Another concern is that cancers can become resistant to drugs. To better understand this process, we have generated cancer cells that are resistant to drugs called HSP90 inhibitors. We hope to identify pathways and genes that play a role in drug resistance, which may inform future drug design programs. Clinical and Visiting Fellow Dr Itsuhiro Takizawa Research Assistants NHMRC Project Grant • Characterisation of the Grb7 protein involved in cellular stress and cancer, Wilce/Price/Gorospe (2011–2013). Enhancement of invasive cancer cell growth of human mammary epithelial cells (MCF10A) when both H-Rasv12 oncogene and activated Heat Shock Factor-1 (HSF1) are produced at the same time. Ms Genevieve Dall Mr Samuel Hawthorne Ms Shelley Hedwards Ms Hayriye Hussein Dr Brindi Niranjan Mrs Michelle Richards Mrs Hong Wang Bio-Resource Co-ordinator www.med.monash.edu.au/biochem/staff/price.html Dr Melissa Papargiris PhD Students Cellular Signalling and Human Disease Laboratory Our goal is to understand how cell communication networks (cellular signalling) are altered in obesity, type 2 diabetes, immune diseases and cancer. Research Assistants Our laboratory uses rodent, fruit fly and cell-based models to study the role of protein tyrosine phosphatases (PTPs) in tyrosine phosphorylation-dependent signalling pathways implicated in normal biological processes and in the development of human disease. A key interest of our laboratory is delineating the roles of PTPs in the control of body weight and glucose homeostasis and in the development of obesity and type 2 diabetes. We are interested in the regulation of insulin signalling in peripheral tissues, leptin and insulin signalling in the brain, and how inflammation contributes to the development of diabetes and obesity. PhD Students We also study the control of T cell signalling and how PTPs can contribute to the development of auto-immune disorders such as type 1 diabetes, rheumatoid arthritis and inflammatory bowel disease. Research Fellows Dr Stephanie Decherf Dr Esteban Gurzov Dr Troy Merry Dr Benjamin Shields Dr Florian Weide Dr Mary Zhang Ms Sock Hui Chew Ms Katja Lowe Ms Teresa Tiganis Ms Bree Buszard Mr Kim Loh Professor Gail Risbridger Deputy Dean (Special Projects) Prostate and Breast Cancer Research Program Professor Tony Tiganis • Regulation of insulin sensitivity by reactive oxygen species (2010-2012). • Regulation of insulin signalling and glucose homeostasis by protein tyosine phosphatases (2009-2011). • Regulation of T cell receptor signalling by TCPTP (2009-2011). Awards and Achievements Professor Tiganis • Loh et al., Elevated hypothalamic TCPTP in obesity contributes to cellular leptin resistance. Cell Metabolism, 2011. Nov 2; 14(5): 684-699. • Wiede et al., T cell protein tyrosine phosphatase attenuates T cell signalling to maintain tolerance in mice. The Journal of Clinical Investigation, 2011. Dec 1; 121(12): 4758-4774. Ms Shirin Hussain Ms Roxanne Toivanen Ms Sarah Wilkinson We conduct basic and clinical research into the three conditions that affect the prostate gland: prostate cancer, benign prostate hyperplasia and prostatitis. We study stem cells in prostate and breast cancer and the role that estrogen plays in the onset of prostate disease. Prostate Cancer Foundation of Australia Project Grant Close affiliations with universities, hospitals and other institutes complement the group’s research. We collaborate with researchers and clinicians in consortia, including the Prostate Cancer BioResource, Victorian Prostate Cancer Research Collaboration and Andrology Australia. Awards and Achievements NHMRC Fellowship Grant Ms Toivanen • Male reproductive health including prostate cancer, Risbridger (2011-2015). NMHRC Enabling Grant, Australian Prostate Cancer • Collaboration (APCC) Bio-Resource (currently known as the Commonwealth Bank Australian Prostate Cancer BioResource in partnership with Andrology Australia), Clements/Tilley/Sutherland/Risbridger (2010-2014). NHMRC Project Grants • Defining the role of Activin C in gonadal and adrenal tumorigenesis, Risbridger (2011-2013). • New paradigm for external genitalia development, Risbridger/Hutson (2011-2013). • Novel estrogen therapy for advanced prostate cancer, Risbridger (2010-2011). Health Research Council of New Zealand • Role of Activin C in prostate disease, Elspeth/Nicholson/ Risbridger (2009-2012). Dr de Sousa • 2010/2011 Marshall Prize in Surgical Training, Department of Surgery, Faculty of Medicine, Nursing and Health Sciences, Monash University. • Finalist, Novartis Junior scientist competition. • Recipient of Women in Endocrinology Young Investigator award. • Finalist, US ENDO 2011 Presidential Poster Competition, Boston, US. Ms Wilkinson • Deakin University award: best oral presentation at the 2011 ASMR Victorian Student Research Symposium. • Third prize, MBio Graduate School 3 Minute Thesis Competition final. • Defining stromal-cancer cell interactions for xenografting human prostate cancer, Risbridger/Taylor/Berman (2010-2012). • Characterising the beneficial effects of estrogen on the prostate gland, Risbridger (2011). ARC Grant • Keeping stem cells on track: maintaining organ and tissue homeostasis, Risbridger/Taylor (2009-2011). Australian Cancer Research Foundation Equipment and Infrastructure • The establishment of the ACRF Centre for Cancer Genomic Medicine, Williams/Hertzog/Watkins/Jenkins/ Risbridger/Gillespie/Simpson/Fuller (2011). Prostate Cancer Foundation of Australia and Cancer Australia (co-funded) • Mechanisms of abiraterone resistance in prostate cancer, Davis/Risbridger/Nelson/Taylor/Mainwaring (2010-2012). Complex arrangement of prostatic stromal cells in experimental models of prostate cancer. Image: Ms Hong Wang. Prostate Cancer Foundation of Australia and Cancer Australia Concept Grants • The potential of serine protease inhibitors to inhibit cancer promoting affects of cancer associated fibroblasts in prostate cancer, Pike/Britt/Risbridger (2011-2012). • Identifying progenitor cells in prostate tumour stroma, Garget/Risbridger (2010-2011). www.med.monash.edu.au/anatomy/research/prostate-breast-cancer.html We are also interested in defining the roles of PTPs in tumour development, in particular, in breast and colon cancers. NHMRC Principal Research Fellowship • Professor Tiganis (2011-2015). NHMRC Project Grants • Regulation of hypothalamic insulin and leptin signaling by TCPTP (2011-2014). • Characterisation of TCPTP as a tumour suppressor (2010-2012). 18 www.med.monash.edu.au/biochem/tiganis-lab.html PTP1B and TCPTP attenuate signalling in obesity. 19 Cardiovascular Disease Cardiovascular disease kills one Australian every 11 minutes* >> What causes hypertension, heart failure, atherosclerosis, stroke and kidney disease? >> How is blood pressure regulated? >> How can we better treat cardiovascular diseases, or prevent them from occurring? *Heart Foundation www.heartfoundation.org.au/information-for-professionals/ data-and-statistics/Pages/default.aspx Annual Report 2011 Cardiovascular Disease Associate Professor Kate Denton Associate Professor Roger Evans Dr Michelle Kett Cardiovascular and Renal Physiology Our group studies how the kidney, heart and vascular systems are regulated. NHMRC Senior Research Fellowship Cardiovascular disease remains the greatest health challenge facing society today. It significantly decreases quality of life for millions of Australians. As integrative physiologists, we study the complex interactions of body systems as a whole. We use sophisticated multi-disciplinary approaches to better understand normal physiology and disease processes. We visualise the cardiovascular system and study its function at all levels, from interactions between specific molecules to the integrated organism. We aim to reduce the burden of cardiovascular disease by identifying the mechanisms causing hypertension, heart failure and kidney disease. NHMRC Project Grants In 2011, we achieved the following: • Salt and cardiovascular disease: Does acute salt sensitivity convey greater cardiovascular risk? (2008–2011) • Discovered new targets for the treatment of pregnancy -induced hypertension, the most common complication of pregnancy that threatens the health and well-being of mother and child; • Case-control study of hypertension in a disadvantaged rural community in India (2011–2013). • Renal AT2R’s are a therapeutic target for the treatment of hypertension in women (2010–2012). • Kidney tissue hypoxia: a common pathway to renal failure (2010–2012). • ACE-2 and diabetic complications (2009–2011). • Underlying mechanisms of cardiovascular disease (2009–2011). National Heart Foundation of Australia Fellowship • Dr Michelle Kett (2008–2013). • Identified renal factors that make the blood pressure of certain individuals sensitive to high salt intake and obesity; National Heart Foundation of Australia (Grants-in-Aid) • Demonstrated that there are sex-differences in adult heart function in offspring with intrauterine growth restriction – even in the absence of hypertension; • Glomerular number deficit does not, on its own, explain the programming of hypertension (2010–2011). • Role of the renin-angiotensin system vasodepressor pathways in pregnancy (2011–2012). Dr Amany Abdelkader Dr Lucinda Hilliard Dr Reetu Singh Research Assistants Ms Lisa Donnet Ms Rebecca Flower Dr Oded Kleifeld Research Officers Dr Sanjaya Kuruppu Dr David Steer Dr Rui Zeng Research Assistants Ms Iresha Hanchapola Ms Josie Lawrence Ms Shane Reeve PhD Students Dr Megan Rees Ms Fei Tieng Ms Kunkun Zhang Our results indicate that peptidases play important roles in blood pressure regulation: they are shed from the cell surface, inactivate vasodilator peptides and also generate vasoconstrictor peptides from inactive precursors. Therefore, by manipulating the expression, cell surface location and activities of these enzymes, we can potentially control cardiovascular function. ARC Centre of Excellence • Structural and Functional Microbial Genomics, Adler/ Coppel/Meeusen/Hertzog/Whisstock/Rossjohn/Smith (2009–2013). ARC Discovery Grant • Structural and functional alteration of red blood cells by Babesia parasites, Cooke/Smith/McElwain/Narla (2010–2012). Victoria’s Science Agenda Strategic Project Fund • Victorian biomedical imaging capability, Smith/Kirk/ Connelly/Duchesne/Szoeke/Egan/Whitten/Kyrios (2010–2013). Awards and Achievements Professor Smith • Member, Federal Government (DISSR) Expert Working Group: Promoting and Maintaining Good Health, Infrastructure Road Map 2011. • Member, BioImaging External Advisory Board, ESFRI Roadmap for Research Infrastructures, Euro-Bioimaging Project, 2011-. • Member, Advisory Board, South-East Asian Observatory. NHMRC Enabling Grant • Imaging and therapeutic medical beamline for the Australian Synchrotron, Smith/Lewis/Pearson/ Hausermann (2009–2012). • Melanocortin regulation of reproduction, Clarke/Smith (2009–2011). NHMRC Program Grant • Control of proteases in infectious, degenerative and cardiovascular disease, Whisstock/Bird/Buckle/ Bottomley/Pike/Smith (2008–2012). • Developed a mathematical model of oxygen transport in the kidney; Research Officers Research Fellow We are especially interested in the peptidases that line the blood vessels. These enzymes can generate and break down peptide hormones which are involved in the regulation of blood pressure. Our long-term goal is to understand which physiological and disease-causing factors control the expression and cell surface location of these peptidases. We work with the structural biology group and medicinal chemists to design and characterise specific enzyme inhibitors of potential therapeutic value. We use proteomics-based technologies to study both the type and levels of enzymes that are expressed on the surface of the cells lining blood vessels. Professor Ian Smith Pro Vice-Chancellor (Research and Research Infrastructure) NHMRC Project Grant • Identified components of the renin angiotensin system that contribute to diabetes-induced kidney damage; Dr Russell Brown Dr Gabriela Eppel Dr James Pearson Dr Niwanthi Rajapakse We aim to characterise and better understand how peptide metabolising enzymes control cardiovascular function. • Associate Professor Denton (2008–2012). • Demonstrated that there are sex-differences in the way in which the renin-angiotensin system, a major regulator of arterial pressure, regulates kidney function, which may protect women from developing cardiovascular disease; Research Fellows Peptide Biology and Proteomics Laboratories • Showed how kidney oxygen levels are altered in response to changes in oxygen delivery and oxygen consumption; • Determined what causes the kidney to be starved of oxygen despite restoration of blood flow after kidney transplantation; and Distribution of α-MSH in the arcuate nucleus and pituitary gland by in situ hybridization and immunohistochemistry. (A): Neurons express POMC mRNA in the sheep arcuate nucleus; (B): MSH staining in the pars intermedia, PI; (C): MSH cells in the pars distalis, PD, are distributed in scattered clusters. PN: pars nervosa. 3V: third ventricle. www.med.monash.edu.au/biochem/research/projects/petptidebiol.html www.med.monash.edu.au/biochem/facilities/proteomics/index.html • Identified a candidate growth factor that may help repair damaged kidneys. The normal decrease in blood pressure seen during pregnancy requires the presence of the angiotensin type 2 receptor (AT2R). PhD Students Mr Xiaochu Cai Mr Mathew Jenkins Mr Yugeesh Lankadeva Ms Katrina Mirabito Ms Melissa Tjongue www.med.monash.edu.au/physiology/research/bloodpressure Honours Students Ms Yi Ching (Peggy) Chen Mr Vatche Douzmanian Ms Debra Fong Mr Sarabjit Hansra Ms Priyadharshani Kalaignanasundaram Mr George Konstantinidis Ms Fiona Lewis Ms Kristen Moore Ms Jennifer Ngo Ms Pei Chen (Connie) Ow Ms Laura Wirth 22 23 Annual Report 2011 Cardiovascular Disease Vascular Biology and Immunopharmacology Group Heart attacks and strokes occur when cardiac or brain tissue is deprived of blood due to the blockage of an artery. We aim to identify the disease pathways within the blood vessel wall that lead to blockages, as well as inflammatory mechanisms that cause cell death. We are interested in whether the immune system can be regulated by drugs, vaccines or stem cells, to prevent or minimise damage from heart attacks and strokes. We have shown that the Nox2 oxidase protein makes excess oxygen radicals in cardiovascular diseases. By comparing the development of artery lesions in fat-fed mice with mice deficient in Nox2 oxidase, we discovered that oxygen radicals released by this protein contribute to artery hardening before heart attacks occur. This free-radical production is markedly increased in brain arteries, which may limit blood flow – even in healthy blood vessels. Research Fellows Dr Brad Broughton Dr Klaudia Budzyn Dr Sophocles Chrissobolis Dr Stephanie de Dios Dr Courtney Judkins Dr Barbara Kemp-Harper Dr Alyson Miller Dr Stavros Selemidis Research Assistants Mr Henry Diep Ms Elizabeth Guida Mrs Elizabeth Hooker Mr Suresh Kaushik Ms Kate Maxwell PhD Students Ms Vanessa Brait Ms Michelle Bullen Mr Michael De Silva Mr Craig Harrison Ms Jacqueline Ku Ms Sandy Lee Mr Jeffrey Moore Ms Jennifer Ravera Ms Ravina Ravi We have discovered evidence to suggest that males are less able to recover from brain damage following stroke than females. This is because more oxygen radicals are released by Nox2 oxidase in males in brain-affected tissues. Therefore, it is important to develop new drugs that inhibit Nox2 oxidase for patients at risk of heart attacks or stroke. NHMRC Senior Research Fellowships • Associate Professor Sobey (2010–2014). • Dr Drummond (2011–2015). Associate Professor Chris Sobey Dr Grant Drummond NHMRC Project Grants • Does a novel estrogen receptor worsen stroke outcome? Sobey/Broughton (2011–2013). • Role of a Down syndrome-related protein in stroke outcome, Sobey/Pritchard (2010–2014). • Are novel nitric oxide mimetics protective in vascular disease? Kemp-Harper/Drummond/Ritchie/Miller (2010–2012). • Aberrant oligosaccharide processing of Nox2-oxidase as a mechanism of vascular oxidative stress in atherosclerosis, Drummond/Sobey (2009–2011). Lecturer • Regulation of vascular tone by kynurenine, Stocker/Sobey (2009–2011). Dr Tracey Gaspari High Blood Pressure Research Council of Australia Research Fellowship • Dr Chrissobolis (2011–2013). Heart Foundation Grants-in-aid • Aldosterone and the mineralocorticoid receptor in cerebrovascular disease, Sobey/Chrissobolis (2011–2012). • Pharmacological inhibition of Ly6Chi monocyte entry into the artery wall as a novel treatment for atherosclerosis, Drummond/Sobey/Ricardo (2010–2011). Dr Emma Jones Research Fellow Larkins and Heart Foundation Fellow Dr Antony Vinh Research Assistant Ms Iresha Welungoda Integrative Cardiovascular Pharmacology Group Professor Robert Widdop Head (Research), Department of Pharmacolgy We are interested in novel treatments for hypertension, atherosclerosis and stroke, with an emphasis on drug targets associated with the renin-angiotensin system. Therefore, our research shows that angiotensin II regulation is a highly complex process. We have also identified novel drug targets for cardiovascular diseases which oppose the view that angiotensin II evokes only excitatory effects. Excessive amounts of the hormone angiotensin II can over stimulate unique binding sites in the heart and blood vessels called AT1 receptors, causing high blood pressure. The AT1 receptor can be blocked by molecules in the ‘sartan’ family, which are used to treat hypertension, heart disease and other cardiovascular complications. However, our research suggests that stimulating other angiotensin-related sites may counteract the negative effects of high angiotensin II levels. Other sites include AT2 and Mas receptors, and enzymes such as ACE2 and IRAP. Indeed, the parent hormone angiotensin II is metabolized in the body to smaller fragments which may then act as endogenous activators at lessconventional sites. NHMRC Project Grants • Central AT2 receptor stimulation improves stroke (2011–2013). • Renal angiotensin type 2 receptor is a therapeutic target for the treatment of hypertension in women (2010–2012). Heart Foundation Grants-in-Aid • Targeting insulin regulated aminopeptidase/AT4 receptor in the treatment of cardiovascular disease (2011–2012). • Novel AT2 receptor-selective peptides (2010–2011). PhD Students Ms Sanja Bosnyak Ms Damie Phua Ms Sonja Tesanovic Honours Students Mr Tyrone Barnes Mr Antony Sutherland Cancer Council of Victoria Project Grant • Novel pharmacological targets for suppression of tumour angiogenesis, Selemidis/Williams/Drummond (2010–2012). NHMRC Career Development Award • Dr Alyson Miller (2009–2012). NHMRC CJ Martin Overseas Postdoctoral Training Fellowships • Dr Budzyn (2007–2011). • Dr Chrissobolis (2005–2011). NHMRC Peter Doherty Australian Postdoctoral Training Fellowship • Dr de Dios (2008–2011). MSc Student Mr Janahan Dharmarajah Honours Students Mr Chris Chan Ms Quynh Dinh Mr Ian Harrison Ms Rushita Kalidindi Ms Shalini Krishnan Ms Kim Taylor 24 Cellular localisation of Nox isoforms through a cross section of artery. A zoomed view of a cell shows the subcellular localisation of each enzyme complex. From Drummond, G.R. et al., Nature Reviews Drug Discovery, 2011. 10: 453-471. www.med.monash.edu.au/pharmacology/research/vbig.html Summary of the regulatory mechanisms controlling the synthesis, metabolism and cardiovascular actions of angiotensin II and its related family of peptides. www.med.monash.edu.au/pharmacology/research/intergrative-cardio-pharm.html 25 Developmental Biology Understanding how organisms grow and develop from a single cell >> What genes control embryonic, stem cell, cancer and organ development, and tissue repair? >> How does a mother’s diet in pregnancy affect her child’s long-term health? >> What are the causes and consequences of premature birth? >> How do steroid hormones increase the survival of premature babies? >> How can we develop stem-cell based treatments for lung-related diseases? >> How do sperm develop and function, and what are the causes of male infertility and testicular cancer? >> How do inflammation and the immune system contribute to eye diseases? >> How do genes contribute to brain and immune system changes in individuals with Down syndrome? Newborn mouse heart, showing cell membranes (green), cell proliferation (red), nuclei (blue) and proliferating cardiomyocyte nuclei (pink). Image: Ms Kom Yin and Mr Jonathan Bensley. Annual Report 2011 Developmental Biology Epithelial Regeneration Laboratory Research Fellow Dr Katja Horvay Research Assistants Ms Helen Lescesen Ms Emma Murphy PhD Students Ms Lisa Kass Ms Genevieve Kerr Mr Rui Liang Honours Student Ms Sivan Elishav Dr Helen Abud Our research centres on understanding how stem cells control cellular growth and differentiation in the epithelial lining of the intestine, and how disruptions in this process cause intestinal disease. NHMRC Project Grants The intestinal epithelium or bowel lining is a regenerative tissue that is constantly renewed throughout life via a small population of stem cells. We are interested in defining the mechanisms controlling intestinal stem cell differentiation and how a balance between cell division and the production of specialised, differentiated cell types is normally established in the intestine. Intestinal diseases and abnormalities are common clinical problems that can lead to the loss of epithelial tissue in infants and adults. In contrast, colorectal or bowel cancer can develop when there is an overproduction of epithelial tissue. The molecular and cellular processes that control growth in the intestine are crucial yet poorly understood. • The Impact of Wnt signalling on spermatogenesis (2011–2013). Our laboratory is studying how several signalling molecules regulate intestinal stem cells, including Snai-1 and DNp73. The expression and function of Snai-1 and DNp73 are also being studied in bowel cancer tumour models. • Building an intestine: manipulating regeneration of the epithelium (2011–2013). We study fetal kidney development, the impact of suboptimal kidney development on fetal and adult health, and kidney regeneration following disease. NHMRC Development Grant • Nephron endowment: are more nephrons necessarily better? Bertram/Kett/Armitage/Caruana (2010–2011). Ms Rebecca Douglas-Denton In 2011 we: (1) studied the effects of gestational diabetes on kidney development; (2) developed a new magnetic resonance imaging method for visualising and quantifying glomerular number and size in whole kidneys; (3) investigated the relationship between body size and podocyte number in humans; (4) studied the effects of specific genes and feto-maternal environmental factors on urinary tract development; and (5) investigated how risk factors for chronic kidney disease impact on kidney microanatomy, including glomerular number and size. PhD Students NHMRC Project Grants • Functional studies on the role of DNp73 in stem cells and cancer (2011–2013). Research Fellows Dr Georgina Caruana Dr Luise Cullen-McEwen Research Officer Dr Reetu Singh Research Assistant The intestinal epithelium is a monolayer of cells that is constantly renewed throughout life via a small population of stem cells. This image shows a crypt from the small intestine where all nuclei are stained (blue) and stem cells highlighted (green). Ms Sarah Henry Ms Stacey Hokke Dr Victor Puelles Mr Kenneth Walker Mr Ryan Wood-Bradley Honours Student Ms Shughla Satari Summer Student www.med.monash.edu.au/anatomy/research/epithelial-regeneration/index.html Developmental Origins of Obesity Related Hypertension PhD Students Mr Benjamin Barzel Ms Sarah Henry Ms Stacey Hokke Mr Ryan Wood-Bradley Masters Student Ms Aurora Elisaia The prevalence of obesity and related diseases are rising worldwide due to a combination of adult risk factors. The environment encountered in utero may also affect the way that fetuses grow, making them more susceptible to developing obesity and hypertension in later life. We study the role of the brain, sympathetic nervous system and kidney in the development of obesity-related hypertension in adulthood. We also examine how being born to a diabetic mother or one who consumed a diet high in fat or folic acid in pregnancy affects fetal kidney development and adult disease. National Heart Foundation Grants-In-Aid Monash Fellowship • How might exposure to maternal fat rich diets during development ‘programme’ the development obesity related hypertension? (2007–2012) • Hypoxia is the common pathway to renal disease, Evans/ Bertram/Schlaich/Gardiner/Smith/Phillips (2010–2012). • New insights into the role of renal endothelial dysfunction in the pathogenesis of glomerular injury and renal fibrosis, Li/Bertram (2010–2012). Research Assistants Ms Anna Dick Ms Kom Yin PhD Students Mr Jonathan Bensley Ms Oksan Gezmish Ms Vivian Nguyen Mr Paul Lombardo Ms Megan Sutherland Ms Vladislava Zohdi www.med.monash.edu.au/anatomy/research/devorigins-obesityrelatedhypertension.html Associate Professor Mary Jane Black We study how exposure to adverse factors in early life (such as maternal malnutrition, vitamin D deficiency and premature birth) can increase disease risk in adulthood. We study how these factors influence the growth of the baby whilst in the mother’s womb and then subsequently how they affect long-term renal and cardiovascular health. • Nephron endowment: Are more nephrons necessarily better? (2010–2011) Optical projection tomographic image of a kidney from a 14 day old fetus of a diabetic mouse. This kidney is abnormal, with two ureters (pink shaded) and ureteric trees (silver shaded) developing within the one kidney. Human kidney glomerulus, showing podocytes (green), endothelial cells (red) and nuclei (blue). Image: Dr Victor Puelles. Cardiovascular and Renal Developmental Programming • How does maternal diet during pregnancy programme offspring obesity related hypertension?: A pivotal role for the sympathetic nervous system (2011–2012). • A neurogenic basis of obesity hypertension: Role of adipokines and ghrelin in regulating sympathetic vasomotor activity (2009–2011). Heart Foundation www.med.monash.edu.au/anatomy/research/kidneydevelopment.html Dr James Armitage • Ocular perfusion pressure: A modifiable risk factor for glaucoma (2009–2011). • Novel methods for promoting organ development and growth, Ricardo/Bertram/Wallace (2010–2012). • Human podocyte depletion, glomerular hypertrophy and glomerulosclerosis, Bertram/Hoy (2010–2013). Ms Georgina Taylor NHMRC Project Grants Professor John Bertram Head, Department of Anatomy and Developmental Biology Kidney Development, Pathology and Regeneration Honours Student Ms Danica Vojisavljevic It is important to understand how these early life insults affect heart and kidney growth, since the functional units of these organs (the cardiomyocytes and nephrons, respectively) are only formed during early development. A reduced complement of these functional units at birth is likely to adversely impact on cardiac and renal health. NHMRC Grants • Does maladaptive remodelling of the heart and vasculature in response to preterm birth lead to long-term cardiovascular risk? Black/Polglase (2011–2013). • Why is the kidney vulnerable to preterm birth? Black/Hoy (2011–2014). Newborn mouse heart, showing cell membranes (green) cell proliferation (red), nuclei (blue) and proliferating cardiomyocyte nuclei (pink). Image: Ms Kim Yin and Mr Jonathan Bensley. www.med.monash.edu.au/anatomy/research/cardio.html 28 29 Annual Report 2011 Developmental Biology Developmental and RNA Biology Pulmonary Development and Programming Group Dr Peter Boag We are interested in the role of gene regulation in reproduction. Specifically, we study how specific pathways and molecular machines drive RNA metabolism and development. Research Fellow Dr Lloyd Low PhD Students Mr Gregory Davis Ms Madhu Sharma Masters Student Ms Tasha Mendes Our group studies how early life factors such as the intra-uterine environment and premature birth can affect the developing lungs and increase the risk of childhood and adult respiratory illnesses such as asthma and chronic obstructive lung disease. Recently, there has been a fundamental shift in the way biologists think about the role of RNA. No longer is RNA considered an intermediary between gene and protein synthesis. Instead, it is now clear that RNA is an extremely important point of complex regulation of gene, which significantly affects cellular function. Research Fellows We use the non-pathogenic roundworm C. elegans as our model system to discover conserved pathways that regulate mRNA translation, which are relevant to mammals. Dr Robert DeMatteo Dr Takushi Hanita Dr Foula Sozo NHMRC Project Grant Ms Natasha Blasch Ms Judy Ng Research Assistants • Post-transcriptional gene regulation in RNA-granules (2010–2012). PhD Students Dissected C. elegans gonad stained for DNA (blue) and two proteins (red and green) involved in RNA regulation. Image: Ms Madhu Sharma Sengupta. Ms Anzari Atik Ms Sheen Bouch Ms Nadine Brew Ms Noreen Ishak Ms Megan O’Reilly Honours Student Ms Danica Vojisavljevic www.med.monash.edu.au/biochem/staff/boag.html Environmental factors that can persistently alter lung structure and function include: the fetus receiving inadequate nutrients via the placenta, maternal cardiovascular disease, maternal smoking and alcohol consumption, and respiratory infections during infancy. Preterm birth affects 10% of all pregnancies and can also affect lung development as a result of ventilator-induced lung injury and inhalation of high oxygen levels. Therefore, we are studying how these environmental factors alter lung development and increase the risk of respiratory illness following preterm birth, and how they can be prevented. NHMRC Program Grant We study specific steroid and growth factor hormones in the developing human lung, which are important in extremely premature babies. Steroids and other endocrine hormones help to maintain the normal function of bodily organs and tissue systems. Their inappropriate action can lead to common adult human diseases such as hypertension, heart failure and metabolic syndromes. Research Fellow Dr Daniel Bird Research Assistant Ms Judy Ng PhD Students Ms Nisha Antony Ms Kirstyn Carey Ms Sasha Firsova Mr Fredrik Olsson Honours Students Ms Tiffany Choo Ms Teresa Le Steroid hormones exert their effects through intracellular steroid protein receptors and are members of the nuclear receptor super-family of ligand-dependent gene regulators. We are studying their signalling pathways in the developing lung (underdeveloped in preterm babies), liver, immune system (leukaemia) and brain (depression). We are also assessing their potential use in stem-cell based treatments for a range of lung-related diseases. The development of lung-like cells would be a major advance for the treatment of injured lungs both in preterm babies and in adults with respiratory disorders. We are also investigating how these hormones regulate genes expressed in the lung, liver, fat and brain. NHMRC Research Fellowship • Senior Principal Research Fellow (2011–2015). Associate Professor Timothy Cole NHMRC Project Grant • Does caffeine affect the development of the very immature brain: Dose response relationship? (2010–2012) Cerebral Palsy Foundation Grant • Can erythropoietin treatment provide long-term protection against inflammation-induced brain injury? (2010–2012) We are also interested in how the developing brain, heart, blood vessels and kidney are affected by intra-uterine conditions and premature birth. By understanding how organs develop and are affected by early life factors, our aim is to develop strategies that could prevent or treat serious respiratory diseases and related disorders. • Improved respiratory support and outcomes for very preterm babies (2011–2015). Steroid Endocrinology and Respiratory Development Laboratory Professor Richard Harding Small conducting airway (bronchiole) from an adult mouse exposed to a high level of oxygen for 7 days after birth. The bronchioles of adult mice briefly exposed to high oxygen levels in infancy have greater amounts of airway smooth muscle and fewer bronchiolaralveolar attachment points. These changes may help explain why impaired lung function is common in children and adults born prematurely. Image: Megan O'Reilly. www.med.monash.edu.au/anatomy/research/pulmonary.html NHMRC Program Grant • Improved respiratory support and outcomes for very preterm babies, Hooper/Davis/Doyle/Harding/Cole/Moss (2011–2015). Endothelial Cells and Kidney Regeneration Dr Jinhua Li We study the role of endothelial cells in kidney injury and regeneration in different disease settings. We have generated an endothelial cell-labelled mouse line to study how endothelial cells become fibroblasts, cells that cause kidney scarring. We are also testing the efficacy of a candidate new drug to treat kidney scarring. Research Assistants Ms Xinli Qu Mr Jun Yao Regulation of the lung surfactant protein D gene (Sftpd) by the Creb1 transcription factor in the developing mouse lung and skin. Sftpd expression is nearly totally absent in Creb1-deficient (-/-) mice. In another project, we are investigating how a novel and potent fat molecule plays critical roles in kidney repair and endothelial cell regeneration. Our research into TGF-β/Smad signalling indicates that protein modification triggers the development and progression of kidney disease, suggesting its therapeutic potential in kidney, liver, lung and heart fibrosis. NHMRC Project Grants • Resolvin E1 is a novel anti-inflammatory and anti-fibrotic lipid mediator for the treatment of chronic kidney disease (2010-2012). • New insights into the role of renal endothelial dysfunction in the pathogenesis of glomerular injury and renal fibrosis (2010-2012). Normal (green) and damaged (red) kidney cells. NHMRC Career Development Award • (2010–2013) www.med.monash.edu.au/anatomy/staff/fellows/jinhuali.html 30 31 Annual Report 2011 Developmental Biology Testis Growth and Germ Cell Development Laboratory We study how sperm develop normally from pluripotent precursor cells during fetal and juvenile life, what molecules are involved in this process, and what factors reduce fertility and cause testicular cancer in humans. Research Fellows Dr Catherine Itman Dr Yoichi Miyamoto Dr Guillaume Morin Dr Wendy Winnall Dr Julia Young Research Assistants Ms Elizabeth Richards Ms Penny Whiley Mr Chin Long Wong PhD Students Mr Arash Arjomand Dr Badia Barakat (PhD awarded August 2011) Ms Genevieve Kerr Mr Andrew Major Ms Laura Tubino Honours Students Ms Hoey Koy Ms Jessica van Gent Ms Anmei Vuong Visiting Scientist Dr Shi-feng Li We investigate how growth factors, including activin, hedgehog and Wnt proteins, signal to drive development of sperm precursors, and promote the growth of somatic cells that form the testis. We discovered that the activin A protein acts to creates a balance between the number of spermatogonial cells and the size of their niche in the growing testis. In this way, activin A controls events that establish the potential for sperm production in adult life and thereby determines adult fertility. Professor Kate Loveland The Ocular Immunomorphology Group • Nuclear roles for importin alpha proteins, Loveland/ Miyamoto/Hecht/Yoneda (2008–2012). We study the development of the eye, and how inflammation and the immune system contribute to eye diseases. Awards and Achievements Projects currently underway in our laboratory include: ARC Discovery Project Professor Kate Loveland • Co-convenor of TGFβ Down Under 2011, Melbourne Australia. Monash Early Career Grant • Are nanotubes a novel means of cell-cell communication in the immune system? Chinnery/McMenamin (2011). • The role of monocyte-derived cells in corneal inflammation; • The role of microglia in diabetic retinopathy; • American Society for Andrology Council member, 2011–2014. Research Fellows Dr Catherine Itman • Society for Reproductive Biology – University of Newcastle Early Researcher Award semi-finalist. PhD Students With increasing rates of human infertility and testicular cancer, there is worldwide concern that exposure of the developing testis to endocrine disruptor chemicals in our environment interferes with the events required for normal sperm formation. Cross-talk between these key growth factors and reproductive hormones is now an important focus of our studies which will uncover how genetics and environment influence male health. Our recent discoveries have revealed that altered activin signalling can also govern the pace of puberty onset, with precocious puberty an increasing concern in human populations. Professor Paul McMenamin Dr Holly Chinnery Dr Jelena Kezic Mr Kevin Su Men Chang Ms Xiangting Chen Mr Yashar Razavi Dr Nina Vagaga (Lions Eye Institute) Research Assistants Dr Aaron Magno (LEI) Ms Manpreet Sidhu • The role of macrophages in age-related retinal degeneration; • How membrane nanotubes improve cell-cell communication in the immune system; • Eye evolution in marsupials to better understand the structure and function of the eye; and • Eye development and how macrophages (white blood cells) remodel the retina and lens. We also collaborate with research partners at the Lions Eye Institute, in Perth; University of Western Australia; and The Centre for Eye Research Australia, Melbourne. NHMRC Project Grants • Do resident immune cells cause retinal damage in diabetes? (2010-2012) • Role of Toll-like receptors in corneal inflammation (2009-2011). We also study the importin family of proteins that ferry other proteins into the cell nucleus and thereby control cellular maturation. We have recently discovered that importins also work inside the nucleus to control gene expression, both in normal cells under stress, and in sperm precursors. A fundus picture of the retina in a mouse whose microglia express Green Fluorescent Protein. The vessels are made visible by the intravenous injection of a red fluorescent dye. www.med.monash.edu.au/anatomy/research/ocular.html NHMRC Senior Research Fellowship • Professor Loveland (2009–2013). NHMRC Project Grants • The impact of Wnt signaling on spermatogenesis, Loveland/Abud (2011–2013). Sperm producing tubules of mouse testis, showing SPC1 (red), importin alpha 2 (green) and chromatin (blue). Image: Andrew Major. • Development of specific activin antagonists for therapeutic applications, Harrison/Loveland (2011–2013). • Activin in testis development and disease, Loveland/ Meachem/Hedger (2009–2011). www.med.monash.edu.au/biochem/staff/loveland.html 32 33 Annual Report 2011 Developmental Biology Male Infertility and Germ Cell Biology Laboratory We study sperm development and function and the causes of human male infertility. Dr Kathleen DeBoer Dr Duangporn Jamsai Dr Adam Koppers Approximately 1 in 20 Australian men are infertile and for the majority of these individuals there is no specific diagnosis. Sperm development is a fascinating process that requires the co-ordinated activation of thousands of genes. It involves stem cell renewal, meiosis, cell changes and complex posttranslational mechanisms, which regulate sperm function. We use models of infertility and cell biology assays to define key proteins and pathways for fertility. This research has direct implications for the diagnosis of human infertility, and the development of therapies and contraceptives. Research Assistants NHMRC Senior Research Fellow Post-doctoral Fellows Mr Brett Clark Mr Francesco Marino Ms Jo Merriner Ms Anne O’Connor Ms Stephanie Smith PhD Student Ms Jennifer Lo Honours Students Ms Rebecca D’Sylva Ms Danielle Rhodes • (2009–2013) NHMRC Project Grants • A new model of asthenospermia and a candidate gene for multiple ciliopathies (2010–2012). • The mechanism of spermatid differentiation – A link to tumour suppression (2010–2012). • The Australian Phenome Bank (2010–2011). • Australian Centre for Vertebrate Mutation Detection (2007–2011). Victorian Government Department of Innovation and Regional Development • Partner Institutions: Monash University, Walter and Eliza Hall Institute Institute of Medical Research, The University of Melbourne (2007–2011). Department of Education of Education, Science and Technology • Institutions: The Australian National University, Monash University, Walter and Eliza Hall Institute of Medical Research, Menzies Institute, Queensland Institute of Medical Research, The University of Melbourne Centenary Institute, Hanson Institute and Animal Research Centre (2007–2011). • Human sperm-oocyte interaction (2009–2011). Dr Koppers • 2011 International Society of Andrology Travel Award. • Upgrade of the Clayton SP5 multiphoton microscope to an upright configuration suited to small animal, organ and whole-mount tissue imaging, Harper/Marcelle/ Lackmann/Bourne/Currie/McMenamin/Loveland/ O’Bryan/Verkade/Bowman/Burke/Warr (2011). Research Fellow Dr Alicia Corlett PhD Students Ms Katherine Martin Mr Yong Yu • Role of a Down syndrome-related protein in stroke outcome, Sobey/Pritchard (2010–2014). • The role of the Down syndrome-related gene DSCR1/ RCAN1 in learning and memory, Pritchard (2010–2011). www.med.monash.edu.au/biochem/staff/pritchard-melanie.html • 2011 Outstanding Trainee Award, American Society of Andrology. Organogenesis Laboratory • A novel DNA damage repair protein as a regulator of DNA double strand break repair and genome integrity, O’Bryan/Jamsai/Ormandy/Handel (2011–2013). Monash IVF Research Grant • Studies on the genetic basis of male and idiopathic infertility, and the trans-generational health of children conceived through ART, O’Bryan/McLachlan/Jamsai (2010–2011). Deutsche Forschungsgemeinschaft International Training Group Funding www.med.monash.edu.au/anatomy/moiraobryan.html Adult neurogenesis in the mouse brain. The dentate gyrus in the hippocampus of an adult mouse brain is shown, with neurones (blue) and newly formed neurones (green). Fondation Jérôme Lejeune Project Grant ARC Discovery Project • Male Reproductive Health and Disease. German participants: Meinhardt/Bergmann/Chakraborty/Fijak/ Linn/Middendorff/Steger/Weidner/ Baumgart-Vogt/ Paradowska/Schagdarsurengin. Australian participants: Loveland/Allan/Hedger/McLachlan/O’Bryan/O’Donnell/ Stanton/Risbridger/Sinclair (2011). We use genetically-modified mice to study the functions of the DSCR1 and ITSN1. Both proteins regulate important cellular signalling pathways. By studying mice that either over-express the gene (as a model of Down syndrome) or have the gene ‘turned off’, we are building a picture of how DSCR1 and ITSN1 contribute to brain and immune changes associated with Down syndrome. NHMRC Project Grant Awards and Achievements Professor O’Bryan • Appointed fellow of the Society for Reproductive Biology. Dr Melanie Pritchard We aim to determine how over-expression of the genes DSCR1 and ITSN1 cause abnormalities associated with Down syndrome. We primarily focus on the brain, but also study how elevated levels of DSCR1 lead to abnormal immune function in Down syndrome. In addition, we examine how DSCR1 protects against brain damage during stroke. The Australian Phenomics Network Infrastructure Grants NHMRC Enabling Grants • Cysteine-rich secretory protein regulation of ion channels in male fertility and prostate cancer (2010–2012). NHMRC Equipment Grant Down Syndrome Research Laboratory Professor Moira O’Bryan Research Officer Dr Kieran Short Research Assistant Ms Lynelle Jones The mouse testis, showing microtubules (green), microtubuleprocessing enzyme (red) and nuclei (blue). PhD Students Ms Sally Ip Ms Cecilia Naranjo-Golborne Ms Tia Di Tommaso Dr Ian Smyth Our laboratory studies the developmental cues important for the development of the skin and kidney. Human Frontier Science Project Grant Using a number of animal models of human disease such as Fraser syndrome and Harlequin ichthyosis, we are investigating the biochemical processes which cause these conditions. At a fundamental level we utilise an imaging technique called Optical Projection Tomography to study the mechanisms which drive branching of the developing kidney. Together with our international and local colleagues, we are modelling this process spatially and mathematically. We also collaborate with the Wellcome Trust Sanger Institute to identify novel mouse models of skin and kidney disease. Awards and Achievements • Modelling kidney development over space and time, Little/McMahon/Smyth/Byrne (2011–2013). Dr Ian Smyth • Wellcome Trust Image award. • Eureka Science Photography finalist. Dr Kieran Short • Wellcome Trust Image award. NMRHC Project Grants • Role of the 72 kDA 5-phosphatase in developmental disease, Mitchell/Smyth/Dyson (2010–2012). • The role of the transporter ABCA12 in lipid metabolism and atheroclerosis, Smyth/Kile/Sviridov (2009–2011). ARC Future Fellowship • Using mouse genetics to understand skin development and cell biology (2011–2014). ARC Discovery Project Grant • A knockout approach to identifying genes involved in epidermal development and homeostasis, Smyth/ Bradley/Watt/Jackson/Martin/Headon/Ramiro-RamirezSolis (2010–2012). Imaging the developing mouse lung using Optical Projection Tomography. www.med.monash.edu.au/anatomy/research/cutaneous.html 34 35 Drug Design Understanding how hormones, drugs, venoms and other molecules act on cells This information can be used to: >> Design drugs that target specific receptors >> Test drug action >> Test the harmful effects of venoms and toxins Annual Report 2011 Drug Design Professor Patrick Sexton Professor Arthur Christopoulos Professor Roger Summers Professor Nigel Bunnett Drug Discovery Biology Laboratory We study how drugs, hormones and natural chemicals act at the surface of human cells. The optimum functioning of living cells, and consequently the health of the entire organism, depends on how cells respond to physical and chemical stimuli such as hormones and neurotransmitters, which bind to specific cell surface receptor proteins. G protein-coupled receptors (GPCRs) are the largest superfamily of all receptors – about 2% of the human genome and are the targets for nearly 40% of therapeutic drugs currently used. We aim to understand how GPCRs are modulated, so we can identify novel approaches for drug discovery. We investigate GPCR structure and function, including naturally occurring receptor variants; signaling via G proteins and downstream messenger systems; interaction of receptors with regulatory proteins; novel allosteric GPCR interactions; biased signalling and modelling of GPCR-ligand interactions. We use relevant GPCR models to understand treatment of metabolic, cardiovascular, inflammatory and central nervous system disorders. NHMRC Fellowships • Australia Fellowship, Professor Bunnett (2011–2016). • Principal Research Fellowship, Professor Sexton (2009–2013). Monash Venom Group ARC Discovery Grants We study the mode of action of venoms and toxins from Australasian and overseas reptiles, snakes and jellyfish. • Understanding allosteric modulation and functional selectivity at G protein-coupled receptors (GPCRs), Christopoulos (2011–2013). • Predictive modelling of ligand binding pockets in G protein-coupled receptors, Sexton (2009–2011). ARC Linkage Grant • Relaxin: molecular mechanisms of cardioprotection, Summers (2011–2013). Research Fellow Associate Professor Geoff Isbister (Adjunct) Research Officer Monash Fellowship Dr Nicki Konstantakopoulos • Dr Canals (2010–2015). PhD Students NIH RO1 Grants • Regulation of cellular responses to neuropeptides, Bunnett (2011–2012). • Protease signaling to the nervous system, Bunnett (2011–2012). VENI Fellowship • Dr Lane (2010-2012). Awards and Achievements Professor Summers • Honorary Professorial Research Fellow, Florey Neuroscience Institutes (2009–2012). Professor Wayne Hodgson Head (Teaching and Research Training, Department of Pharmacology (to November 2011) Deputy Dean (Education) (from December 2011) Ms Carmel Barber Mr Janeyuth Chaisakul Mr Andrew Hart Ms Rachelle Kornhauser Mr Usswin Santiphanpithaks Mr Jure Skejic Honours Students Mr Steven Fernandez Mr Kaijun Lin Ns Nami Nagar Mr Daryl Yang We determine how venoms and toxins affect vital physiological processes and how to counteract these effects using antivenoms or novel therapeutic approaches. We also identify venom components which may be used for the development of new drugs to treat human diseases. ARC Grants • Molecular toxinology of Australia’s lesser known venomous snakes (2010–2012). • Evolutionary venomics: venom system diversification in the animal kingdom (2007–2011). The Hermon Slade Foundation • Box jellyfish toxins: investigating novel protein structure and function (2010–2012). A comparison of the fangs from the Australian Coastal taipan, Oxyuranus scutellatus (left) and the West African gaboon viper, Bitis rhinoceros (right). Images: Venom Supplies, Tanunda. • Cephalopod venom evolution (2008–2011). www.med.monash.edu.au/pharmacology/research/venoms-toxins.html • British Pharmacological Society Fellow (2005–). • Senior Research Fellowship, Professor Christopoulos (2008–2012). • CJ Martin Fellowship, Dr Gregory (2011–2014). • CJ Martin Fellowship, Dr van der Westhuizen (2011–2014). • CJ Martin Fellowship, Dr Sato (2010–2013). • CJ Martin Fellowship, Dr Halls (2008–2012). • CJ Martin Fellowship, Dr May (2008–2012). • CDA Fellowship, Dr Hutchinson (2009–2012). NHMRC Program Grant • Understanding G protein-coupled receptors: accelerating discovery from concept to clinic, Sexton/Christopoulos/ Summers (2009–2013). NHMRC Project Grants • Molecular characterisation of the glucagon-like peptide 1 receptor, Sexton/Simms/Canals (2011–2013). • Bitopic ligands as a novel approach to G protein-coupled receptor selectivity, Lane (2011–2013). • Understanding new drug paradigms at M1 muscarinic receptors, Canals (2011–2013). Distinct transmembrane domain interactions govern selective signalling of GPCRs. Mutation of the polar serine residues S155 or S186 of the GLP-1 receptor to Ala leads to distinct effects on agonist promoted signalling via cAMP accumulation, intracellular Ca2+ mobilisation or phosphorylation of ERK (left panels). Molecular models of the transmembrane region of the receptor indicate that each residue is likely to be involved in interactions in different subdomains of the receptor, resulting in unique conformational changes upon mutation (right panels). These data are helping us unravel how GPCRs translate extracellular signals to intracellular responses. • Understanding the pharmacoregulation of the extracellular calcium sensing receptor, Christopoulos (2009–2011). www.pharm.monash.edu.au/research/mips/ddb/index.html Personal Assistant Ms Jessica Richardson Senior Lecturer Dr Richard Loiacono Research Fellows Dr Meritxell Canals Dr Chris Choy Dr Bronwyn Evans Dr Sebastian Furness Dr Karen Gregory Dr Michelle Halls Dr Caroline Hick 38 Dr Dana Hutchinson Dr Martina Kocan Dr Rob Lane Dr Katie Leach Dr Lauren May Dr Masaaki Sato Dr David Thal Dr Celine Valant Dr Emma van der Westhuizen Dr Denise Wootten Research Assistant Mr George Christopoulos Technical Assistants Mr Thomas Coudrat Mr John Merlin Dr Anne Stewart Ms Christine Yeo PhD Students Ms Anna Davey Ms Briana Davie Mr Peter Keov Ms Cassandra Koole Ms Vindhya Nawaratne Ms Kavita Pabreja Mr Mohsin Sarwar Ms Emilia Savage Ms Su Suratman Ms Georgina Thompson Mr Adriel Wen Masters Students Ms Stephanie Catus Ms Alla Abdul-Ridha Honours Students Mr Sam Dentry Ms Linzi Lim Mr Nathan Ryan Mr Christopher Siwek 39 Immunology Understanding how the body defends itself from pathogens, and how this defence sometimes goes wrong and causes allergies, asthma and autoimmune diseases >> How do diet and microorganisms in the gut contribute to autoimmune diseases and cancer? >> How can we develop anti-inflammatory drugs for asthma and autoimmune diseases? >> How can we harness the immune system to treat cancer and autoimmune diseases? The formation of germinal centres (white) in the spleen after immunisation. Germinal centres are specialised lymphoid structures that produce high affinity antibodies and generate B cell memory, which are the basis of vaccination. Image: Louis Tsai. Annual Report 2011 Immunology Immunology and Biotechnology Autoimmune diseases and asthma are increasing in developed countries, and we seek to understand and treat these conditions based on new approaches, including the manipulation of diet and composition of gut microbes. We are also developing new anti-inflammatory drugs that target new molecules or cells involved in asthma and autoimmune diseases. Research Fellows Dr Lauren Binge Dr Nina Chevalier Dr Laurence Macia Dr Eliana Marino Dr Remy Robert Dr Alison Thorburn Research Assistant Mr Laurent Juglair Honours Students Ms Caroline Ang Ms Josepha-Marie Cox Ms Kate Rogers Ms Megan Splittgerber Diet affects the make up of gut flora. We found that a metabolic product from the fermentation of fibre – short chain fatty acids – has a marked anti-inflammatory effect on inflammatory responses. It does this by binding to a receptor expressed on immune cells called GPR43. We have uncovered how GPR43 affects immune responses. It interacts with chemoattractant receptors, macrophages and dendritic cells and plays a role in epithelial cell integrity. We have developed new monoclonal antibodies to treat human inflammatory diseases. These are in various stages of preclinical development. Promising new drugs under development target the chemoattractant receptor molecules CXCR7, CXCR3, CCR6, GPR43 and BAFF receptors. For this work, we collaborate extensively throughout Monash, including the Australian Regenerative Medicine Institute. We have developed an extensive capability around antibody engineering and hope to develop three additional antibodies for human clinical trials. NHMRC Australia Fellowship • Professor Mackay (2010–2015). Molecular Immunomodulation Laboratory Professor Charles Mackay We study the molecular mechanisms of immune responses and how the immune system can be harnessed to treat autoimmune diseases and cancer. NHMRC Project Grant • Regulation of immune and inflammatory responses by short chain fatty acids and GPR43 (2010–2013). NHMRC Development Grant • Development of anti-CXCR7 mAbs for the treatment of fibrosis, Mackay/Sierro (2010–2012). NHMRC Program Grant • Cellular and molecular studies of the adaptive immune response in health and disease, C Mackay/Sprent/ Goodnow/Basten/Cook/F Mackay/Vinuesa/Tangye/ Brink (2007–2011). Research Assistant Mr Yew Ann Leong PhD Student Mr Louis Tsai International Honours Students Mr Anthony Chen Ms Crystal Chen Murine bone marrow derived neutrophils were plated onto glass coverslips and stained for mouse beta-catenin (green), F-actin (red) and the nucleus (blue). www.med.monash.edu.au/immunology/research/imm-inflammation.html Antibodies are used by the immune system to identify and destroy pathogens. Generation of pathogen-specific neutralising antibodies are the basis of most successful vaccines. However, self-reactive antibodies (autoantibodies) bind self-antigens, interfere with normal cellular functions and cause autoimmune disease. We and others have identified a new subset of immune cells, called follicular helper T (Tfh) cells, which drive antibody maturation and memory formation. Therefore, Tfh cells are crucial for antibody-based vaccination and play an important role in antibody-mediated autoimmune diseases. We study how these cells differentiate and function in genetically-modified mice, and hope to design strategies to either promote antibody responses or suppress autoantibody responses. Dr Di Yu NHMRC Career Development Award • The biology of follicular helper T cells, Yu (2011–2014). ARC Discovery Project Grant • MicroRNAs and the control of T lymphocyte differentiation, function and malignant transformation, Yu (2011–2013). Ramaciotti Establishment Grant • A novel strategy of regulating follicular helper T cell function to promote antibody responses (2011). Larkins Fellowship (formerly known as Monash Fellowship) • Dr Yu (2011–2015). For tumour cells to be rejected, several immune cells need to be activated: T lymphocytes, dendritic cells and Natural killer cells. Interleukin IL-21 (IL-21) is emerging as a key molecule in this process, regulating specific cells. Preclinical research indicates that IL-21 has antitumour effects, an approach that is being tested in human clinical trials. Here, we study genetically-modified mice that have IL-21 and IL-21 receptor replaced with human IL-21 and its receptor. We hope to develop new approaches to boost anti-tumour immunity through the IL-21 pathway for clinical application NHMRC Project Grants • Cytokine structure and mechanisms of a superagonist antibody, Yu/Beddoe (2011–2013). • Specialised subsets of T follicular helper cells in the control of infection and immune pathology, Vinuesa/ Yu/Liston (2011–2013). The formation of germinal centres (white) in the spleen after immunisation. Germinal centres are specialised lymphoid structures that produce high affinity antibodies and generate B cell memory, which are the basis of vaccination. Image: Louis Tsai. www.med.monash.edu.au/immunology/research/molecular-immunomodulation.html 42 43 Immunology and Stem Cells How can stem cells >> Form medically relevant cells? >> Be delivered to sites of injury, inflammation and disease? >> Regenerate damaged tissue? >> Be used as a model for Huntington’s disease? >> Avoid immune rejection? What role does the thymus play in automimmunity, immunodeficiency, and tissue and stem cell rejection? Kidney cells in culture. Annual Report 2011 Immunology and Stem Cells Neuroimmunology Research Fellows Dr Sara Litwak Dr Leon Moussa Dr Chris Siatskas Dr Bi Song Dr Guizhi Sun Research Officers Ms Noami Canpanale Ms Daniella Herszfeld Research Assistants Mr Ashley Emerson-Webber Ms Aude Sylvan Ms Nadege Veron Ms Kerry Webber PhD Students Ms Sally Cain Ms Courtney McDonald Ms Natalie Payne Dr Martin Short, MBBS, FRACP Professor Claude Bernard Multiple sclerosis (MS) is a debilitating disease that affects the central nervous system (CNS). Although the precise triggers remain elusive, the ultimate end point of the disease is the destruction of nerve axons and myelin, two key cellular components of the CNS involved in the conduction of nerve impulses. At present, there is no cure for this severe neurodegenerative condition. Therefore, there is an urgent need to understand the causes of this and other central nervous system disorders, so that more effective treatments can be developed. California Institute for Regenerative Medicine and Victorian Government As an important first step, we have developed a novel approach to detect harmful cerebrospinal fluid molecules and brain proteins from patients with multiple sclerosis. Using this assay, we have identified novel reactive CSF proteins in the brain and tested their effects in experimental models of chronic-active MS. A variety of new therapeutics could possibly emerge from these studies. Awards and Achievements We have also manipulated adult skin cells from MS patients and converted them into stem cells, using a technique called induced-pluripotent stem cells. We showed that these MS stem cells could differentiate into neurons and myelinproducing cells. By reprogramming cells from patients with MS into nerve cells, we may increase our understanding of this debilitating disease. Immune Regeneration Laboratory Associate Professor Ann Chidgey Deputy Laboratory Head • Engineering immune tolerance by stem cell-derived thymic regeneration (2010–2012). The Eva and Les Erdi AUSiMED Fellowship in Neurological Diseases The Immune Regeneration Laboratory studies the structure, development and function of the thymus under normal and pathological conditions, including age- and drug-induced degeneration. We aim to use this knowledge to overcome clinical conditions such as autoimmunity, immunodeficiency and transplant rejection, including rejection of stem cell therapies. • Generation of induced pluripotent stem cell lines from multiple sclerosis patients (2009–2013). The Cure MS Fellowship in Neurological Diseases • Cell therapy for neurodegenerative diseases by progenitor cells derived from induced pluripotent stem cells (2010–2012). Professor Bernard • Guest Professor, BaYi Brain Hospital, Beijing, China. The thymus is the site of T cell production, and plays a vital role in educating the immune system to distinguish between ‘self’ tissue and foreign invaders. However, the thymus undergoes profound age-related atrophy, linked to the rise of sex steroids in puberty, as well as chemotherapy, radiation, HIV infection and environmental factors. • Guest Professor, Kunming Medical University, Beijing, China. • Keynote speaker at the 2011 Life Science Symposium, Kunming, China. • Keynote speaker, 2011 China-Australia Symposium on Stem Cell Research, Beijing General Hospital, Beijing, China. • Invited speaker, Grantee Meeting of the California Institute of Regenerative Medicine, San Francisco, US. NHMRC Program Grant • Invited speaker, Australasian Autoimmunity Workshop, Brisbane, Australia. • Innovative stem-cell based strategies to establish immune tolerance (2007–2011). • Invited speaker, California Institute of Regenerative Medicine/Australia Workshop, Melbourne. Professional Officer Mr Mark Malin Personal Research Assistant/Senior Research Officer Ms Samantha Harris Personal Assistant/ Technical Assistant ARC Discovery Grants Ms Luciana Thompson • Nerve regeneration using light responsive hydrogels and stem cells (2010–2012). Research Fellows Dr Tracy Heng Dr Natalie Seach • Molecular characterisation of stem cell differentiation and oocyte maturation using synchrotron infared spectroscopy and atomic force microscopy/Raman imaging (2008–2012). ARC Linkage Grant The Baker Foundation AussiMed • Stem cell therapies for neurological diseases (2009–2013). Biogen Idec Clinical Fellowship • The fate of bone marrow derived cells following acute inflammation of the central nervous system (2009–2011). Californian Institute for Regenerative Medicine/ Victorian Government Department of Innovation, Industry and Regional Development • Thymus based tolerance to stem cell therapies (2010–2013). • Neural stem cells as a developmental candidate to treat Alzheimer’s disease (2009–2012). CSIRO-OCE Grant • Combinatorial assembly of bioactive peptides to generate selective biofunctional materials (2011–2013). Neo Stem Cell (Hong Kong) Contract Research Funding • Research and development of neonatal stem cells (2011). Taif University, Kingdom of Saudi Arabia Collaborative Research Program • Training TAIF scientists in stem cell research (2011). Awards and Achievements • Stem Cell Awareness Day public seminars, Federation Square, Melbourne. NHMRC Overseas-based Biomedical Fellowship • (2011–2014) NHMRC Program Grant Ms Maree Hammett Ms Lisa Spyroglou • Innovative stem cell-based strategies to establish immune tolerance and tissue repair (2007–2011). Technical Officers ARC Linkage Grant PhD Students • Application of direct protein transduction of stem cell factors to reprogram mouse and human somatic cells into pluripotent stem cells (2009–2011). Mr Marco Barsanti Ms Adrienne Calder Ms Danika Khong Ms Louisa Layton Ms Joanna Lim Ms Jessica Morison Mr Anthony Park Ms Chew-Li Soh Ms Kahlia Wong • The use of neural stem cells as a therapeutic tool in neurological disorders (2007–2011). In 2011, we studied the following research projects: pathways involved in thymic and bone marrow ageing and sex-steroid withdrawal-mediated regeneration; identification and analysis of a putative adult thymic stromal progenitor cell; differentiation of human embryonic stem cells to form thymic stromal cells; isolation of mesenchymal stem cells (MSC) from clinically viable sources; the application of isolated MSC to treat asthma; and development of a clinically relevant approach to improve the success of transplantation with foreign cells and tissues. Research Assistants Ms Jade Barbuto Ms Jade Homann • Proteomic analysis of central nervous system inflammation in multiple sclerosis (2010–2012). Professor Richard Boyd Director, Monash Immunology and Stem Cell Laboratories Australian Stem Cell Centre – Adult Stem Cell Collaborative Stream (4) • Adult thymic stem cells (2010–2011). Australian Stem Cell Centre – Collaborative Stream (3) • Characterisation of respiratory and thymic epithelium derived from the in vitro differentiation of pluripotent stem cells (2009–2011). Distribution of Pax9 (green) in the thymus of an embryonic mouse at day 14 of gestation. Pax9 is a protein that activates genes involved in the formation of the thymus. Image: Mr Marco Barsanti. Honours Students Adult skin cells taken from an MS patient, which have been converted into stem cells, can become myelin-producing cells. These cells have on their surfaces two common CNS myelin proteins: CNPase (green) and myelin basic protein (red). The stem cell nucleus is stained light blue. Ms Michelle Burns Mr Michael Hun www.med.monash.edu.au/miscl/research/immune-regeneration.html www.med.monash.edu.au/miscl/research/neuroimmunology.html 46 47 Annual Report 2011 Immunology and Stem Cells Embryonic Stem Cell Differentiation Laboratory Professor Andrew Elefanty Professor Ed Stanley We study the directed differentiation of human embryonic stem cells (hESCs) into medically relevant human cells, including blood cells (blood disorders), blood vessel cells (cancer and hypertension), respiratory epithelium (lung diseases) and pancreatic beta cells (type 1 diabetes). ARC Special Research Initiative in Stem Cells (Stem Cells Australia) To assist us, we have generated geneticallymodified hESCs that express green or red fluorescent proteins when they form cell types of interest. We then isolate these fluorescent cells and study their function. • Methods for detection and elimination of residual human embryonic stem cells in a differentiated cell product (2009–2012). Cardiac Stem Cell Laboratory We aim to isolate and expand cardiac cells derived from human embryonic stem cells, then simulate heart disease in the laboratory and improve our understanding of this disorder. • Program 2: Directed differentiation of pluripotent stem cells, Hilton/Elefanty/Stanley/ Nielsen/ Haylock/Nilsson/ Little (2011–2018). CIRM-Victorian Government Early Translational Research Award Research Assistants Ms Deevina Arasaratnam Ms Kathy Koutsis Mr Rhys Skelton • Stem cell derived cardiomyocytes: tools for investigating cardiac disease, Elliott/Kaye/Pouton/Haynes (2009–2011). • Professor Elefanty (2011–2015). Ms Lisa Azzola Ms Freya Bruveris Ms Sonia Holland Mr Roy Lee Ms Robyn Mayberry Ms Koula Sourris NHMRC Project Grant • Characterisation of human embryonic stem cell differentiation to haematopoietic progenitors and stem cells, Elefanty/Stanley/Nilsson/Haylock (2011–2013). Human cardiomyocytes derived from embryonic stem cells. Cells express green fluorescent protein (green), the transcriptional regulator NKX2-5 and have a functional contractile apparatus (blue). Qatar National Research Fund Project Grant • Stanley/Tabrizi/Elliott/Elefanty/Costa (2010–2012). NHMRC/JDF Special Program Grant in Type 1 Diabetes • Derivation of pancreatic beta cells from embryonic stem cells (2008–2012). www.med.monash.edu.au/miscl/staff/david-elliott.html ARC Discovery Grant • Developing the basis for a quality control platform for human pluripotent stem cells and their differentiated derivatives, McNaughton/Stanley/Elefanty/Tobin (2011–2013). Panel of images showing differentiated hESC lines carrying lineage specific fluorescent markers. The indicated genes mark differentiating mesoderm (MIXL1), blood (ErythRED and RUNX1c), heart (NKX2.5), pancreas (INSULIN), lung (NKX2.1) and nerve (NKX2.1). Kidney Stem Cell and Regeneration Laboratory www.med.monash.edu.au/miscl/research/embryonic-stem-cell.html PhD Students Ms Julie Cao Ms Jennifer Durnall Mr Rob Jenny Ms Jacqueline Schiesser Ms Chew-Li Soh Mr Michael Wong Ms Cissy Yu • Isolation, expansion and characterisation of human cardiac progenitor cells (2010–2012). Australian Stem Cell Centre Module 8: Pluripotent Stem Cell Stream • Professor Stanley (2009–2013). Research Assistants NHMRC New Investigator Award • The role of micro-RNAs in human cardiac specification, White/Elliott (2011–2013). NHMRC Research Fellowship Grants Dr Magdaline Costa Dr Antonietta Giudice Ms Tanya Hatzistavrou Dr Claire Hirst Dr Andrew Holland Dr Vanta Jokubaitis Dr Sue Mei Lim Dr Suzanne Micallef Ms Elizabeth Ng Dr Katerina Vlahos We have generated a genetically-modified human embryonic stem cell line that expresses green fluorescent protein in heart muscle cells. Using this line, we have isolated earlyprecursor heart cells as well as more mature cardiomyocytes. These cells allow us to study how heart cells behave and cardiac diseases develop. NHMRC Project Grant We also collaborate with Dr David Elliott, who generates heart muscle cells, and with Professor Richard Boyd, who studies how hESCs can differentiate into thymic epithelium. Research Fellows Dr David Elliott We aim to develop new stem cell-based therapies that may offer alternatives for patients with end-stage kidney disease undergoing kidney transplantation and long-term dialysis. NHMRC Development Grant We are working on the following projects: • Postnatal therapy for organ growth and repair (2011–2013). Generation of stem cells from patients with kidney disease Research Fellow Dr Bi Song Research Assistant Ms Emerald Surrao Mr Junli Zhuang PhD Students Ms Maliha Alikhan Mr Adrian D'Arcy Ms Christina Jones Mr Timothy Williams Ms Andrea Wise Associate Professor Sharon Ricardo We recently published the first report showing that stem cells, called iPS cells, can be generated from human kidneys. In the future, these patient-specific iPS cell lines could potentially be used for drug testing and personalised medicine, where treatment decisions are based according to an individual patient’s disease profile. These stem cells will also help us to better understand how kidney disorders develop. • Novel methods for promoting organ development and growth (2010–2012). NHMRC Project Grant Awards and Achievements Associate Professor Ricardo • Amgen Basic Science Award, Australia and New Zealand Society of Nephrology 2011. A novel therapy for babies with kidney defects There is growing evidence that genes involved in kidney development also play a role in kidney regeneration, ‘switching on’ kidney repair following injury. We are testing a protein for clinical trials that can promote kidney growth and maturation. If successful, this protein could potentially treat unborn babies with kidney defects when currently there is no cure. We also hope to develop strategies that promote kidney ‘self-repair’ and study blood-derived immune cells, which play an important role in this process. Kidney cells in culture. www.med.monash.edu.au/miscl/research/renal-regeneration.html 48 49 Infectious Diseases Understanding how microorganisms cause human or animal diseases >> How do parasites, bacteria, viruses and fungi cause diseases? >> How do immune cells respond to infection? >> How can we produce better drugs or vaccines against infectious organisms? >> How can we better treat asthma and other respiratory diseases? Malaria parasites bursting out of a human red blood cell. Image: Professor Brian Cooke. Annual Report 2011 Infectious Diseases Biology of Granzymes and Granzyme Inhibitors We are interested in the killing mechanism of cytotoxic lymphocytes, immune cells that eradicate virus-infected or cancer cells from the body. Professor Phillip Bird Acting Head of School NHMRC Project Grant • The impact of granzyme B on cytotoxic T cell migration through tissue (2011–2013). To kill abnormal cells, cytotoxic lymphocytes release two key factors: a pore-forming protein called perforin and a protease called granzyme B. Perforin mediates entry of granzyme B into the interior of the target cell, causing death. Research Fellows Dr Dion Kaiserman Dr Alexandra Rizzitelli Research Assistants Ms Cathy Bird Ms Corinne Hitchen Ms Jennii Luu PhD Students Also, these immune cells contain a granzyme B inhibitor, PI-9, which protects them from being killed by granzyme B. Some cancer cells overproduce PI-9, which may be a way to evade the immune system, ensuring their survival. Currently, we are studying the distribution and function of PI-9 within cytotoxic cells in mice lacking this key protein. Honours Student www.med.monash.edu.au/biochem/staff/bird.html Dr Lakshmi Wijeyewickrema Research Assistant Mrs Usha Koul PhD Students Ms Nicole Drentin Ms Renee Duncan Ms Rebecca Fitzpatrick Mr Tang Yongqing • Intracellular survival of Burkholderia pseudomallei and the evasion of autophagy (2009–2011). • Molecular and genetic basis of colistin resistance in Acinetobacter baumannii (2009–2011). • The vaccine potential of live, attenuated leptospiral mutants; ARC Centre of Excellence in Structural and Functional Microbial Genomics • The genetic and structural roles of cell surface molecules of the pathogen Pasteurella multocida, which causes numerous livestock infections, and their role in disease; Australian Poultry CRC • Professor Adler – Director (2005–2013). • Rapid multiplex PCR assay for differentiating Pasteurella multocida serovars (2011–2013). • How LPS loss in Acinetobacter baumannii affects the host immune system; Research Fellows Human cytotoxic lymphocytes migrating through extracellular matrix (Matrigel) produce granzyme B. Dr Elizabeth Allwood Dr Thanatchaporn Bartpho Dr Xenia Gatsos Dr Marina Harper Dr Rebekah Henry Dr Renee Marcsisin Dr Gerald Murray Research Assistants Ms Deanna Deveson Ms Marietta John Ms Kate Rainczuk Research Fellow In 2011, we investigated the following: • Analysis and regulation of leptospiral virulence factors (2009–2012). • The mechanisms by which the multi-drug resistant, hospital acquired pathogen Acinetobacter baumannii develops resistance to colistin, a ‘last resort’ antibiotic; Ms Aimee Parker Protease Laboratory NHMRC Project Grants • How virulence genes of Pasteurella multocida are regulated; NHMRC Program Grant • Control of proteases in infectious, degenerative and cardiovascular disease (2008–2012). We study how bacteria cause human and animal diseases, and how the body’s immune system responds to infection. • The role of lipopolysaccharide (LPS) and other surface components of Leptospira in leptospirosis infection of animals and humans; How granzyme B is released from cytotoxic lymphocytes and enters target cells is unclear. However, we have identified regions of granzyme B that are required for cell entry, and have shown that its role extends beyond initiating cell death in compromised cells. Our recent results indicate that the enzyme allows cytotoxic lymphocytes to migrate through tissue, and control blood clotting. Mr Jamshaid Ahmad Ms Susan Berkowitz (with James Whisstock) Mr Michael d’Angelo Ms Aminah Giousoh (with James Whisstock) Mr Matthew Mangan Mr Anthony Matthews Ms Monica Prakash Ms Sarah Stewart Ms Sonia Teoh Ms Evelyn Yip (with Steve Bottomley) Dr John Boyce Professor Ben Adler Bacterial Pathogenesis and Immunity Professor Robert Pike Head, Department of Biochemistry and Molecular Biology We study how proteases from bacteria and the human immune system are involved in disease processes. One major focus is the complement system of immunity, which is the first line of defence against pathogens. We also conduct research on periodontal (gum) disease, which is a major cause of tooth loss worldwide and is also associated with other diseases. ARC Linkage Grant The complement system is vital to our immune system, but unregulated complement activation has been linked to many diseases, including cardiovascular and degenerative diseases. We have shown how proteases that initiate complement activation interact with their targets and regulators. This information will help us design molecules that inhibit key processes and combat disease. • The potential of serine protease inhibitors to inhibit cancer promoting effects of cancer associated fibroblasts in prostate cancer, Pike/Britt/Risbridger (2011–2012). • Characterisation of plant cysteine proteases with therapeutic potential, Pike/Whisstock/Song/Mynott (2011–2014). Oral Health Cooperative Research Centre • Antagonists of host receptors and gingipains to prevent progression of periodontal disease (2011–2013). Prostate Cancer Foundation of Australia The oral bacterium Porphyromonas gingivalis is a major causative agent of periodontal disease. It makes proteases that regulate many of the pathogenic activities of the bacterium. We have shown how these enzymes interact with the immune system to cause gum disease. We aim to block key disease-causing molecules with candidate inhibitors. • How Burkholderia pseudomallei, which causes the tropical disease melioidosis, interacts with and evades defence mechanisms inside host cells; and • Potential vaccine candidates for footrot, a serious infection affecting sheep. Shadowed electron microscope image of bacterial cell of pathogenic Leptospira. Image: Annabella Chang. www.med.monash.edu.au/microbiology/staff/boyce.html www.microbialgenomics.net Technical Officers Mr Mark Edmunds Ms Vicki Vallance PhD Students Ms Priyangi Alwis Ms Sadia Deen Ms Deanna Deveson Ms Amy King Ms Jennifer Moffatt Ms Puthayalai Treerat Mr Timothy Witchell Ms Kunkun Zhang Honours Students Ms Hedieh Aklaghi Mr Tim Fitzsimons Ms Cara Nethercott Undergraduate Research Students Ms Bethany Crane Ms Sanvir Maharaj Mr Luke Southey Mr Stephen Watts Academic Visitor Dr Isabelle da Piedade NHMRC Program Grant • Control of proteases in infectious, degenerative and cardiovascular disease, Whisstock/Bird/Bottomley/ Buckle/Pike/Smith (2008–2012). Crystal structures of the catalytic and adhesin domains of a gingipain (upper panel), together with the domain structure of the enzyme (lower panel). www.med.monash.edu.au/biochem/staff/pike.html 52 53 Annual Report 2011 Infectious Diseases Molecular Parasitology Research Fellows Dr Svenja Günther Dr Nicholas Proellocks Research Assistants Ms Donna Buckingham Mr Charles Ma PhD Students Ms Rimi Chakrabarti Ms Sejal Gohil Ms Ghizal Siddiqui Undergraduate Student (MIC3990) Mr Kit Kennedy Autophagy Laboratory Professor Brian Cooke Our group studies how parasites of red blood cells (particularly malaria and babesia) cause disease and death in humans and animals, with the aim to develop new drugs or vaccines. ARC Discovery Project Grant Malaria is central to our research activities because it affects over half of the world’s population, and still kills about 1 million people each year. We also study babesia parasites as these cause a malaria-like disease in cattle, which results in huge economic losses to the beef and dairy industries worldwide. • Malaria and red blood cells (2008–2012). • Structural and functional alteration of red blood cells by Babesia parasites (2010–2012). NIH Program Grant Research Fellows Eukaryotic cells degrade unwanted parts of their internal structure by the process of autophagy (“self eating”). ARC Project Grant In yeast, autophagy acts to remove unwanted or damaged components of these cells and this helps them adapt to starvation or other stresses. • Design and fabrication of molecular machines: the nanomachines of the future, Lithgow/Rossjohn/Devenish/ Martin/Strugnell (2011-2014). Dr Lan Gong Dr Dalibor Mijaljica In 2011, we worked on the following projects: Visiting Scientist Removal of organelles by autophagy Dr Xuelei Li Autophagy in bacterial infection of mammalian cells NHMRC Senior Research Fellowship PhD Students We are studying how the bacterium Burkholderia pseudomallei can successfully survive in infected cells without being destroyed by autophagy. • Function of parasite proteins in malaria infection (2009–2013). Research Assistant Malaria parasites bursting out of a human red blood cell. Ms Tanya D’Cruze Mr Alexander May NHMRC Project Grants Masters Student • Exported malaria kinases and red blood cell remodeling (2010–2012). Honours Student Ms Shu-chin (Alicia) Lai Ms Alexandra Dimitropoulos • SBP1 and altered structure and function of malaria-infected red blood cells (2010–2012). • Autophagy and the nucleus (2009-2011). ARC Super Science Fellowship In mammalian cells defects in autophagy can be linked to pathological conditions, including: microbial and viral infections, neurodegenerative and muscle tissue diseases, and some forms of cancer. Our group has shown that these parasites make red blood cells stiff and sticky, which allows them to lodge in vital organs such as the brain. We identify proteins that cause these changes in red blood cells, so that new prevention and treatment strategies can be developed. Our work is recognised and supported both nationally and internationally. Dr Xiao-Hong Liu Professor Rod Devenish We are trying to better understand how the nucleus is degraded when yeast cells are starved of nutrients. NHMRC Project Grant • How Burkholderia evades autophagy, Boyce/Devenish/ Prescott (2009–2011). ARC Centre of Excellence Grant • Centre of Excellence in Structural and Functional Microbial Genomics, Adler/Coppel/Devenish/Hertzog/ Meeusen/Rood/Rossjohn/Smith/Whisstock (2010–2013). Transmission electron micrograph of RAW264.7 cells six hours after infection with Burkholderia pseudomallei (magnification x600). Intracellular bacteria are observed within single-membrane compartments and not double-membrane autophagic compartments. www.med.monash.edu.au/microbiology/staff/cooke.html www.med.monash.edu.au/biochem/staff/devenish.html Professor John Davies Head, Department of Microbiology (to October 2011) Molecular Analysis of Bacterial Pathogens By studying bacteria that cause infectious diseases in humans and animals, we are working to understand how bacteria and their hosts respond to each other during infectious processes. Research Fellow Dr Catherine Ryan Research Assistant Ms Chen Ai Khoo PhD Students Mr David Allen Ms Ya-Hsun Lin Ms Dervilla McGowan Ms Jessica Phillipps • Regulation of pilus biogenesis in Neisseria (2009–2011). Research Assistant Ms Kher Shing Tan PhD Students Mr. Jhih-Hang Jiang Ms Janette Tong Honours Students Ms Dilini Alankarage Mr Nicholas Clark Mr Sam Palframan www.med.monash.edu.au/microbiology/research/davies.html 54 Mitochondria are essential for the function of our cells. These structures are the powerhouses of the cell, providing the ‘cellular fuel’, ATP. In human cells, mitochondria also regulate other processes, including controlling when a cell self destructs and dies. Failure in mitochondrial processes can cause cancer, and metabolic and neurodegenerative disorders. • Characterisation of Neisserial cell surface adhesins and their role in infection (2009–2011). Neisseria gonorrhoeae. Dr Kip Gabriel We study how mitochondria are impaired during disease. NHMRC Project Grants Disease-causing or pathogenic bacteria inhabit specific sites in the body. They may then invade the host tissue and enter the bloodstream, where they continue to multiply. At each stage, bacteria need to alter the cell surface by switching specific genes on or off. For instance, bacteria produce surface structures to initially latch onto their host, which they may later discard when invading tissues. Also, other bacterial surface components must be present in the bloodstream for bacteria to avoid immune detection. Complete DNA sequences of many pathogenic bacterial genomes are now known. From this information, we can identify genes present in given species, monitor their levels at specific infection stages and understand how these genes are controlled. We can also monitor how the immune system responds to changes on the bacterial cell surface. By understanding these complex interactions, it may be possible to identify new and innovative ways of interfering with infection processes. Mitochondrial Functional and Disease Biology It is now clear that many human pathogens have evolved to ‘hijack’ or ‘disrupt’ mitochondrial processes during infection by sending toxic proteins to these structures. Together with our collaborators, we are investigating how mitochondrial function is regulated by bacteria that cause stomach ulcers and meningococcal disease. We also study mitochondrial dysfunction in early and late-onset Parkinson’s disease. NHMRC Project Grants • Helicobacter pylori VacA toxin: modulation of human mitochondrial function by a bacterial pathogen, Gabriel/ Kwok-Schuelein (2011–13). A mammalian cell showing the endoplasmic reticulum (green) and mitochondria (red). • How does inactivation of PINK1 cause Parkinson’s disease? Cheng/Culvenor/Gabriel (2009–2011). www.med.monash.edu.au/biochem/staff/gabriel.html 55 Annual Report 2011 Infectious Diseases Nuclear Signalling Lab We study the movement inside cells of proteins from viruses that cause Dengue fever, rabies, respiratory disease and AIDS, as well as molecules that play a role in cancer. We are interested in how these medically relevant proteins move into and out of the cell nucleus, the control centre of the cell, how this can be controlled, and how drugs can be targeted to the cell nucleus to combat cancer or correct genetic defects. Research Fellows Dr Mohammad Aljofan Dr Leon Caly Dr Johanna Dean Dr Greg Moseley Dr Stephen Rawlinson Dr Kylie Wagstaff Research Assistants Ms Rebecca Davies Mr Steve Heaton Mr Bevan Hirst PhD Students Ms Arelia Aguilar (visiting) Ms Michelle Audsley Ms Shadma Fatima Ms Henna Kuusisto Ms Kim Lieu (completed) Mr Ivan Ng Ms Sibil Oksayan Ms Caitlin Rowe Ms Linda Wiltzer Honours Students Mr Aaron Brice Mr Callum Lawrence In 2011, we showed that particular nuclear transport proteins play a key role in embryonic stem cell development and drive germ cell differentiation in the testis. We also determined the mechanism that cancer related molecules and some viral components use to be transported into the cell nucleus. Importantly, we developed a strategy to identify new inhibitors of nuclear transport, showing that they can inhibit the replication of viruses such as HIV, the causative agent of AIDS, and Dengue. • Novel technology platform for gene delivery into intact cells, Wagstaff (2011–2013). • New targets for antiviral therapies, Jans/Moseley/Wang (2011–2013). ARC Postdoctoral Fellowship • Dr Wagstaff (2011–2013) Bill and Melinda Gates Foundation Grand Challenges Grant • Viral self-destruct sequences: a novel live-vaccine technology, Moseley/Rawlinson/Jans (2010–2011). Recently, we discovered the following: Senior Collaborator Professor Julian Rood Research Fellows Dr Milena Awad Dr Glen Carter Research Assistants Ms Anjana Chakravorty Ms Michelle Kelly Technical Officers Ms Pauline Howarth Ms Julie Singleton • Professor Jans (2011–2015). PhD Student NHMRC Project Grants • Regulation of subcellular localisation of respiratory syncitial virus M protein: Implications for pathology, Jans/Ghildyal/Bardin (2010–2012). We have developed novel ways to genetically modify the bacterial pathogens Clostridium difficile and Clostridium sordellii of both human and animal origin. We are using this approach to understand how these micro-organisms harness regulatory and virulence factors to cause disease. ARC Discovery Grants NHMRC Senior Principal Research Fellowship • Subcellular trafficking of P proteins of human pathogenic viruses: roles in viral pathogenicity and targeting for therapeutics, Moseley (2011–2013). Clostridial Genetics Laboratory Professor David Jans Mr Edward Rose Honour Students ‘Fast-track’ nuclear transport by the cancer protein PTHrP. PTHrP moves rapidly along microtubules until it reaches the microtubule organising centre (MTOC), where the importin β (β) transporter takes over, and moves PTHrP through the nuclear pore (NPC) into the nucleus. Ms Bliss Cunningham Ms Darshani Jayawardena Ms Lucy Li Ms Rebecca Rabi Laboratory Associate Dr Priscilla Johanesen • Nuclear function of Dengue NS5 protein: Role in disease, Jans/Akkina (2010–2012). • Novel microtubule association sequences from rabies virus: Subversion of antiviral responses and use in drug delivery, Jans (2009–2011). Our lab studies how protein molecules are precisely transported to their correct location within cells. Professor Trevor Lithgow Research Fellows Dr Matthew Belousoff Dr Denisse Leyton Dr Thomas Naderer Dr Hsing-Hui Shen Dr Miguel Shingu-Vasquez Dr Chaille Webb PhD Students Ms Khatira Anwari Ms Nermin Celik Mr Srgjan Čivčiristov Mr Rhys Dunstan Ms Victoria Hewitt Mr Joel Selkrig Professor Trevor Lithgow ARC Super Science Fellowship • Design and fabrication of molecular machines: The nanomachines of the future (2011–2013). 56 Research Fellows Dr Rob Bischof Dr Melissa Burke Dr Michael de Veer Dr David Piedrafita Dr Jill Pleasance Protein transport is central to understanding how diseasecausing microbes build their outer membranes and how they direct toxic proteins into human cells. Protein targeting and transport are both driven by complex molecular machines. Research Assistants Mr Chris Hosking Mr Gary Nguyen Our research addresses how these specialised protein transport machines evolve and the mechanisms by which these transport machines function. PhD Students NHMRC Program Grant • NHMRC program in cellular microbiology (2011–2015). NHMRC Project Grant • Determining how the ability to secrete proteins assists E. coli to cause disease (2009–2011). ARC Federation Fellowship • Molecular machines that drive microbial pathogens (2008–2013). www.med.monash.edu.au/biochem/staff/lithgow.html • We have developed methods by which a pathogen of post-abortive and postpartum females and transplant patients, Clostridium sordellii, can be genetically manipulated. We have shown that the bacterium contains a lethal toxin, TcsL, that is the primary cause of severe disease symptoms; and • Regulation of toxin production in Clostridium difficile, Rood/Lyras (2009–2011). • Virulence mechanisms in hypervirulent epidemic strains of Clostridium difficile, Lyras/Rood/Johnson/Gerding (2009–2011). ARC Discovery Grant • The role of virulence factors of Clostridium difficile in food production animals, Lyras/Rood/Riley/Songer (2010–2012). ARC-Linkage Grant • The development and evaluation of colostrum-derived antibodies for the prevention and treatment of Clostridium difficile infections, Lyras/Rood/Rawlin (2011–2014). • Spores of epidemic hypervirulent strains of bacteria have different surface properties compared to non-epidemic strains, which may play important roles in infection and disease since spores are responsible for infection initiation. NHMRC Project Grants • Host-pathogen interactions in gas gangrene, Rood/Lyras/Awad (2011–2014). Transmission electron microscopy image of Clostridium difficile spores. Biotechnology Research Laboratories A major global issue is the rise of antibiotic resistance in bacterial pathogens. In response to this threat, new drug targets need to be identified and new vaccines need to be developed. Fundamental aspects of bacterial cell biology need to be understood if we are to take creative approaches to defeating these 'new' bacterial pathogens. ARC Federation Fellow • Mutations in a regulatory gene encoding TcdC are important in development of the hypervirulent phenotype in Clostridium difficile and Clostridium sordellii; • How does Clostridium sordellii cause disease in post-abortive, post-partum and transplant patients? Lyras/Rood/Aronoff (2010–2012). www.med.monash.edu.au/microbiology/research/lyras.html www.med.monash.edu.au/biochem/research/projects/nuclearsig.html Protein Targeting Laboratory • Toxin B from Clostridium difficile plays an essential role in antibiotic-associated infections in hypervirulent strains of bacteria; Dr Dena Lyras After some controversy, our model (the 'inside view') is now accepted as the mechanism that human mitochondrial cells have used to evolve from distant bacteria. The major innovations that drove this development took place within the bacterial genome. Reproduced with permission from Alcock et al. Science. 2010. 327: 649–650. Ms Jenna Van Gramberg Mr Chris Hosking Mr Michael Lees Mr Hamish McWilliams Ms Jacqueline Melville Ms Sarah Preston Masters Students Ms Bahar Liravi Ms Trine Meldgaard Honours Students Mr Jibril Ibrahim Mr David Lewis Mr Minh Hung Nguyen Professor Els Meeusen We conduct basic and applied research in infectious and allergic diseases with the aim to develop new vaccines, diagnostics and treatments. ARC Centre of Excellence Grant Helminth (worm) parasites cause debilitating diseases in people living in developing countries and significant production losses in livestock worldwide. However, there are no vaccines that target these parasites. We have identified a key parasite molecule (antigen) that can provide protection against infection. In collaboration with a major industry partner, we have shown that a vaccine based on this antigen can be used in sheep under farm conditions, and are further developing this vaccine for commercial application. ARC Discovery Grant Vaccines also need to be delivered effectively and generate immune responses following injection. By using a unique lymphatic cannulation model, we can now study how antigens flow and are taken up from the injection site by different adjuvants - immune-enhancing agents. By understanding how these adjuvants work, we can design vaccines to treat infectious diseases and allergies. • ARC Centre of Excellence in Structural and Functional Microbial Genomics, Adler/Coppel/Devenish/Hertzog/ Meeusen/Rood/Rossjohn/Smith/Whisstock (2010-2013). • Molecular determinants of an allergic response, Meeusen/O’Hehir (2009-2011). ARC Linkage Grants • Characterisation and development of adjuvants for new generation veterinary and human vaccines, Meeusen (2009-2011). • Development of proto-type vaccine against gastrointestinal nematode larvae, Meeusen (2006-2011). Ministry of Science and Education, SPAIN – National Grant • In vivo depletion of γδT cells and eosinophils and its effects on the resistance of the Canaria Hair Breed sheep against Haemonchus contortus, Gonzalez/Piedrafita/ Meeusen/Molina/Rodriguez/Hernandez (2009-2011). With our collaborators at the Alfred Hospital and Faculties of Engineering and Pharmacy, we are testing new formulations and delivery devices, and developing new diagnostics for the treatment of asthma and other respiratory diseases. NHMRC Development Grant • The Respire™ system: Portable pulmonary delivery platform for rapid, flexible and highly efficient treatment of elderly, paediatric and physically-compromised patients with chronic respiratory diseases, Yeo/ Friend/Morton/ McIntosh/Meeusen (2010-2011). www.med.monash.edu.au/physiology/brl/ Uptake of antigen by different cell types (coloured) after vaccination. 57 Annual Report 2011 Infectious Diseases Molecular Virology We develop modified virus-like particles as vaccination tools and assess their mode of action. Virus-like particles (VLPs) have emerged as successful devices for developing modern vaccines. They are non-infectious multi-protein complexes which elicit highly effective immune responses. Senior Research Fellow Dr Gholamreza Haqshenas Research Fellow Dr Wan-Shoo Cheong PhD Student Ms Michiko Hyakumura Honours Students Mr Minh Gau Ms Natalie Kingston We design modified viral structural proteins containing immune system-stimulating sequences derived from foreign sources. We assess how these recombinant proteins assemble into highly structured multi-protein complexes (VLPs), and study mechanisms of immunogen processing and how long-acting immune responses can be achieved. We have successfully generated VLPs that induce immune responses against the viruses: hepatitis C (HCV), HIV and influenza. We have also identified genetic interactions that occur between key proteins during HCV synthesis. As these protein-protein interactions are attractive targets for antiviral compounds, we are developing screening assays to identify inhibitors which interfere with HCV synthesis. • Recombinant virus-like particles for the delivery of HIV-1 neutralising epitopes arrayed at high density (2010–2011). • High throughput screening assays for the examination of potential inhibitors of hepatitis C virus p7 (2010–2011). Research Fellow Equity Trustees, Harold and Cora Brennen Benevolent Trust PhD Students • Particles with modified structural features as optimised delivery platforms for HIV neutralising sequences (2011). We use molecular genetics to understand how virulence factors are regulated, and how virulence and antibiotic resistance genes move between bacteria. We aim to understand bacterial evolution and pathogenesis, and develop new methods to control and treat bacterial infections in both humans and animals. Senior Collaborator Recently, we discovered the following: Research Fellows • The crystal structure of four proteases from the footrot pathogen, a hoof infection in sheep, goats and cattle; Visiting Scientists A/Prof. Xiang-Dang Du Dr Marianne Gilhuus PhD Students Mr Daniel Andrews Ms Shalini Narayanan Mr Abolghasem Tohidpour The peptidoglycan-binding domain of Helicobacter pylori motility protein B, a component of the bacterial flagellar motor. Department of Innovation, Industry, Sciences and Research, Australia-India Biotechnology Collaborative Fund Project Grant Cancer Council Victoria • Clostridium-directed enzyme prodrug therapy (2010–2012). • Molecular recognition between alkane hydroxylase and rubredoxin in alkane degrading bacteria (2010–2013). Australian Poultry CRC • Vaccine against Clostridium perfringens to protect birds from necrotic enteritis (2010–2012). www.med.monash.edu.au/microbiology/staff/roujeinikova.html US National Institutes of Health Norwegian Research Council Fungal Pathogenesis Laboratory Dr Ana Traven We study how the hospital-acquired human pathogen Candida albicans makes its cell surface, which plays a key role in the disease process. NHMRC Project Grants • Host-pathogen interactions in Clostridial myonecrosis, Rood/Lyras/Awad (2011–2014). • Role of regulatory genes in the control of toxin production in Clostridium perfringens (2009–2011). • Regulation of toxin production in Clostridium difficile, Rood/Lyras (2009–2011). Research Fellows Dr Branka Jelicic (European Group of Eight fellow) Dr Yue Qu • Virulence mechanisms in hypervirulent epidemic strains of Clostridium difficile, Lyras/Rood/Johnson/Gerding (2009–2011). PhD Students Mr Farkad Bantun (with Dr Anton Peleg) Ms Tara Quenault Ms Nathalie Uwamahoro • (2006–2013) • The role of virulence factors of C. difficile in food animals Lyras/Rood/Riley/Songer (2010–2012). We are also interested in the mechanisms that Helicobacter pylori use to cause gastric disease. In collaboration with Dr Terry Kwok-Schuelein, we are analysing the structure of CagA and its role in stomach cancer formation. • Understanding the molecular mechanism of force generation in the bacterial flagellar motor (2010–2014). • The toxin that causes the poultry disease necrotic enteritis is encoded on a conjugative plasmid. ARC Discovery Grant We investigate structure-function relationships in motility protein B, the component of the bacterial flagellar motor (BFM). Many pathogenic bacteria use motility as a mechanism to spread in the host organism and cause disease. However, there is limited structural information about motility proteins that control flagellum rotation, which we hope to address. We have recently established how the power-generating part of the BFM anchors itself to the cell wall. We are now working to understand the molecular mechanism of force generation. ARC Discovery Project (linked with Australian Research Fellowship) • The development and evaluation of colostrum-derived antibodies for the prevention and treatment of Clostridium difficile infections, Lyras/Rood/Rawlin (2011–2014). • Ovine footrot and contagious claw diseases in Norway (2010–2014). ARC Centre of Excellence in Structural and Functional Microbial Genomics Associate Professor Roujeinikova • Japan Society for the Promotion of Science Fellowship. • (2010–2014) ARC Linkage Grant • A novel regulatory gene that modulates virulence in the bacterium that causes gas gangrene; and Honours Students Awards and Achievements ARC Australian Research Fellowship Professor Julian Rood • Clostridium perfringens type B, C, D toxins (2009–2014). • The pathogenesis of infections caused by Clostridium sordellii Lyras/Rood/Aronoff (2010–2012). Associate Professor Anna Roujeinikova Bacterial stress response also plays a role in disease. Together with Professor John Davies, we aim to understand, at both the molecular and structural levels, how the stress response is initiated in Neisseria gonorrhoeae. • These proteases are important virulence factors in ovine footrot; Ms Rachel Adamson Ms Radhika Bantwal Ms Anjana Chakravorty Ms Jocelyn Choo Mr Thomas Hiscox Ms Lee-Yean Low Ms Kate Mackin Mr C. Benjamin Wade Ms Lakmini Weeramantri Ms Jessica Wisniewski Ms Xu-Xia Yan Ms Chai Yee Kua Ms Shelley Lyon Mr Christopher Stubenrauch Dr Hernan Alonso www.med.monash.edu.au/microbiology/research/netter.html We study how bacterial pathogens, particularly anaerobic bacteria, cause disease in humans and animals. Dr Vicki Adams Dr Luminita Badea Dr Trudi Bannam Dr Jackie Cheung Dr Xiaoyan Han Dr Ruth Kennan Dr Versha Rai We use a structural biology approach to understand how medically-important bacteria cause disease. Australian Centre for HIV and Hepatitis Virology Research Functional Biology of Bacterial Pathogens Dr Dena Lyras Structural Biology of Bacterial Virulence Factors Associate Professor Hans Netter Structure of AprV2 protease from Dichelobacter nodosus, reproduced from Kennan et al., PLoS Pathogens, 2010. 6: e1001210. The cell wall is a structure on the surface of C. albicans’ cells, which is required for adherence to indwelling medical devices such as catheters, pacemakers and prosthetic devices, leading to the formation of drug-resistant fungal biofilms. Biofilms are highly resistant to antifungal therapy, resulting in high death rates in infected individuals. In addition to making biofilms, the cell wall also interacts with, and evades the patient’s immune system. We have identified a new system network that links cell wall integrity and antifungal drug resistance in C. albicans with the function of the mitochondria, the powerhouse of eukaryotic cells. This discovery has allowed us to identify new factors which are implicated in the resistance of C. albicans to existing antifungal drugs, and which could therefore be targeted for future drug discovery programs. We have also discovered new C.albicans’ genes that are involved in biofilm development. Scanning electron microscopy image of C. albicans biofilms formed on serum-coated silicone disks. ARC Discovery Project Grant www.med.monash.edu.au/microbiology/research/rood.html 58 • RNA-binding proteins regulate protein targeting and membrane biosynthesis, Traven/Lithgow (2010–2012). www.med.monash.edu.au/biochem/staff/traven.html 59 Medical Imaging and Radiation Sciences Diagnostic Imaging and Radiation Therapy Medical Imaging and Radiation Sciences >> Diagnostic imaging: X-Ray, Ultrasound, CT, MRI and PET >> Functional imaging of cancer Research Assistant Ms Dianne Luc MPhil Students Dr Jeremy Graham Mr Mark Ngo Mr Richard Oates Mr David Robinson PhD Students Mr Nigel Anderson Mr Jason Callahan Ms Shawna Farquharson Mr Brian Lee Mr Paul Lombardo Mr Jonathan McConnell Ms Erica Sturm Dr John Troupis Ms Caroline Wright Dr Michal Schneider-Kolsky Our group collaborates with clinical and academic centres to develop and test new applications in medical imaging and radiation therapy techniques, including X-Ray, CT, MRI, PET and ultrasound. We focus on anatomical and functional cancer detection (breast, lung, head and neck and prostate), musculo-skeletal ultrasound, developing new contrast materials for use in ultrasound, and study biological effects of neonatal cranial ultrasound. In 2011, the group initiated various research studies utilising infra-red thermal imaging for applications in human and animal models. Projects are also ongoing in education, occupational burnout, professionalism and role extension of radiographers and radiation therapists. Awards and achievements Mr Jason Callaghan • CRC Biomedical Imaging Scholarship (2011-2012). FDG PET/CT scans in a patient with a suspected liver tumour. The top row shows a 4D PET/CT scan compared to the standard PET/CT scan on the bottom row. The 4D PET/CT scan shows a large metabolically active tumour indicated by the cross-hairs. This large tumour was not visible on the standard PET/CT scan. This example shows that 4D scanning can successfully correct for a significant artefact caused by respiratory motion. www.med.monash.edu.au/radiography/research Radiation therapist Sarah Everitt treating a patient with radiation therapy. 61 Neuroscience Understanding how the brain interacts with the environment and how it communicates with and controls the tissues and organs of the body >> What changes occur in the brain after a stroke? >> How does the brain interact with hormones in fertility, obesity and stress? >> How do adverse events during pregnancy and birth affect a child’s long-term health? >> How does the brain respond to vision and sound? Nerve cell projections expressing the peptides kisspeptin (green/yellow), neurokinin B (red/yellow) and gonadotrophin releasing hormone (blue) converge at the median eminence, at the base of the brain. Image: Dr Jeremy Smith. Annual Report 2011 Neuroscience Sensory and Cognitive Neuroscience Laboratory Sensory Neuroscience Dr Kathleen Burman We are interested in understanding the nature of the plastic changes that occur in the adult brain after a stroke. Research Assistant Ms Karyn Richardson When a stroke occurs, blood supply to part of the brain is blocked (ischemia), and affected brain cells die from oxygen and glucose starvation. Many stroke victims recover, either partially or completely, suggesting that changes occur that allow undamaged parts of the brain to control function by compensating for the damaged regions. With our stroke research, we study the structural changes that occur in the neural pathways connecting parts of the brain that receive sensory information and the motor areas that then use this information to plan and execute motor commands, after focal ischemic lesions of the primary motor cortex. We are restricting the lesions to this part of the brain because it is the principal region that sends nerve impulses to the spinal cord to accomplish movement. Since there is evidence to suggest a relationship between anatomical changes and functional recovery after stroke, we are also studying whether rehabilitative training can improve physical recovery. Research Fellow Dr Leo Lui Research Officers As part of a study on changes in the motor control pathways following stroke, anatomical tracers are injected into motor areas to track reorganisation of the normal pathways. Here we see cells in the non-lesioned primary motor cortex labelled following injection of a fluorescent tracer in a secondary motor area. Research Fellows Dr Jessica Jacobi (50%) Dr Qun Li (33%) Dr Rui Zeng Research Assistants Ms Teena George Ms Alda Pereira (50%) Ms Alix Rao (50%) Ms Sofie Saleh (50%) PhD Students Dr Kevin Kwok-Lee (MBBS) Dr Matthew Maiden (MBBS) (Co-supervisor, Adelaide University) Mr Steven Yau (Co-supervisor, University of Melbourne) The brain controls hormone secretion from the pituitary gland. In turn, pituitary hormones regulate the function of the endocrine organs: ovaries, testes and adrenal glands. The part of the brain that communicates to the pituitary is the hypothalamus, which also plays a major role in controlling body weight. Dr Markus Hietanen Dr Lauretta Passarelli A/Prof Vahid Sheibani Ms Claire Annunziata Mr Tristan Chaplin Mr Greg Egan Ms Karyn Richardson Ms Amanda Worthy Ms Katrina Worthy • Plasticity of sensorimotor representations in adult primate cortex (2009–2011). Neuroendocrinology is a discipline that relates to the way that the nervous system interacts with and controls the endocrine (hormonal) system of the body. We study how the brain controls reproduction and food intake. This has relevance to fertility and obesity. Visiting Scientists Research Assistants NHMRC Project Grant (New Investigator) Systems Neuroendocrinology Dr Vladimir Dubaj Dr Saman Haghgooie Dr David Reser Dr Richa Verma Dr Hsin-Hao Yu Professor Iain Clarke Head, Department of Physiology United States Department of Agriculture We study how the brain processes sensory information, and how this changes as result of experience. We hope to generate a comprehensive series of ‘circuit diagrams’ of the sensory regions of the mammalian brain, which will help us understand how nerve cells communicate, via electrical signals, what we feel from moment to moment. By understanding these basic brain functions, there is the potential to develop environmental sensors in machines and prosthetic devices that can restore or enhance sensory functions in humans. ARC Discovery Grants • Computational neuroanatomy: Analysis of neural connections in the primate brain, Rosa/Mitra (2011-2013). • Colour visual processing in honeybees: Solutions for decision making in complex environments, Dyer/Rosa (2008-2012). • Understanding how the primate brain processes visual information (2008-2010). ARC Special Research Initiative Grant (Research in Bionic Vision Science and Technology) • Direct stimulation of the visual cortex: A flexible strategy for restoring high-acuity pattern vision, Lowery/Rosa/ Rosenfeld/Rajan et al., (2010-2013). In 2011, we used electrophysiological techniques to obtain the first recordings of neuronal activity in prostriata, a phylogenetically ancient area of the primate cerebral cortex, about which very little is known. Our results demonstrate that this structure ‘fast-tracks’ information from the eyes to brain regions involved in movement, emotions, memory and hearing. It appears that prostriata works as an ‘alert system’, focussing the brain on new and unexpected events occurring in the periphery of the visual field. NHMRC Project Grants • A visual pathway through the limbic cortex (2011-2013). • Physiological bases of audiovisual integration, Rosa/Rajan (2009-2011). PhD Student Dr Yin Yang • Saccadic eye movements and the neural basis of visual perception, Ibbotson/Rosa (2009-2011). Honours Students • Plasticity of the primate cerebral cortex (2008-2010). Ms Amanda Davies Mr Thomas Wicaksono Professor Marcello Rosa NHMRC Enabling Grant (Model Biological Systems) • National non-human primate breeding and research facility, Phelps/Borg/Rosa/Smith (2007-2011). Computer graphic ‘unfolded’ reconstruction of the cerebral cortex of the macaque, showing the spatial distribution of neurones that send connections to area V6Av, a part of the brain that provides visual information for the control of hand movements towards objects. Area V6Av receives most of its inputs from visual areas (V2, V3, V4/DP and MST), and from other areas involved in visual-motor coordination (MIP, PGm, FEF, area 46). The insert is a dorsal view of the intact macaque brain. This study was conducted in collaboration with researchers from the University of Bologna, Italy. • Hypothalamic site of action of kisspeptin in the regulation of growth hormones release in ruminants, Clarke (2011). German Research Community (DFG) www.med.monash.edu.au/physiology/staff/rosa.html • Characterisation of the skeletal effects of the disconnection between the hypothalamus and the pituitary gland in sheep, Clarke/Amling/Pogoda/Beil (2010–2011). Awards and Achievements Professor Clarke • Appointed fellow of the Society for Reproductive Biology. We study two neuropeptides that regulate both energy homeostasis and reproduction: Kisspeptin and gonadotropin inhibitory hormone. In other work, we are examining how the brain controls the expenditure of energy by fat and muscle to overcome obesity. NHMRC Project Grant • Melanocortin regulation of reproduction, Clarke/Smith (2009–2011). ARC Project Grant • Dissecting the impact of stress on reproduction: Novel peptide mediates as inhibitory effects of stress on female reproduction, Tilbrook/Clarke/Hemsworth (2009–2011). University of Mexico Fellowship • Dr Jessica Jacobi (2009–2011). Horizon Science Contract Model showing how cells in the brain interact to regulate appetite and reproduction. From Backholer et al., Endocrinology, 2010. 150: 5488. • Beneficial effects of LoGiCane sugar on glycemic index adiposity and insulin sensitivity in maturing piglets: Implications for human childhood obesity, Clarke (2010–2011). www.med.monash.edu/physiology/staff/clarke.html 64 65 Annual Report 2011 Neuroscience Cell Systems Physiology We focus on understanding how adverse events during pregnancy and birth give rise to diseases in the baby, which remain throughout life. NHMRC Project Grants We investigated the effects of maternal alcohol consumption during pregnancy on the function of blood vessels in the offspring, using a sheep model. Alcohol use alters cardiovascular function significantly, affecting arteries and blood pressure control mechanisms (Image: Panel A). • Understanding local and regional determinants of EDHF and NO dysfunction in resistance arteries in diabetes (2009–2012). We also study how smooth muscle contraction in the ureter is controlled. Problems in pregnancy can result in obstructed urine flow from the kidney to the bladder in new-born infants. We are interested inhow prostaglandins influence pacemaker ion channels, which are responsible for these contractions (Image: Panel B). Research Fellows Dr Jessica Jacobi (50%) Dr Kelly Kenna Dr Qun Li (33%) Research Assistants Ms Meagan Davies Ms Mary Tonta PhD Students Mr Justin Bourke Mr Shane Chaisakul Ms Melissa Tjongue Oxygen deprivation can occur during the process of birth and result in cognitive and motor deficits in children. The hippocampus is a brain region critical for memory and learning, and is very vulnerable to hypoxia. We found that oxygen deprivation in marmosets had no effect on hippocampal function in females, but function in males was significantly impaired (Image: Panel C). Sensory Neuroscience Associate Professor Helena Parkington Dr Richard Lang Dr Harold Coleman Dr Marianne Tare • How neurosteroid hormones may protect the brain following compromised pregnancy and preterm birth (2011–2013). • How amyloid causes neurodegeneration: The role of transthyretin in familial amyloidotic polyneuropathy (2009–2011). Postdoctoral Fellow Dr Scott Kolbe Research Assistants Ms Gemma Edwards Ms Danielle Prescott ARC Linkage Grant Our lab investigates the neuronal activity in the brain that underlies conscious visual perception. NHMRC Project Grant We record the activity of single neurons in parts of the brain that respond to visual stimuli. By recording data in awake subjects, who can indicate what they perceive, we are able to understand how the brain encodes and assesses the external environment, and how brain activity leads to conscious perception. Human Frontier Science Program: Career Development Award • Neuronal sensitivity and variability underlying perception and action (2011–2013). • Changing sensitivity in a changing world: How do neuronal populations encode dynamic environments? (2010 –2012). In 2011 we investigated how visual perception is affected by recently seen stimuli. We have shown that judgments of motion direction at any point in time are affected by the speed and direction of stimuli seen in the previous few seconds. This indicates that our basic visual sensations are highly malleable and subject to ongoing calibration. The lab is also part of the Monash Vision Group, a cross-faculty initiative involving industry partners that aims to develop a bionic eye. We are pre-clinically testing prostheses to determine how to optimally stimulate the brain’s visual cortex to recreate vision in blind patients. • Novel anti-ageing peptides in the vascular system. NHF Grants-in Aid • Alcohol in pregnancy leads to artery disease in the offspring (2009–2011). University of Mexico Fellowship • Dr Jessica Jacobi (2009–2011). www.med.monash.edu.au/physiology/staff/price.html Premature labour results in the baby being born early and predisposes to complications in later life. We record uterine contractions and electrical activity in tissue obtained from women undergoing caesarean delivery. We have discovered that a particular potassium channel that is involved in suppressing uterine contractions is turned off during labour (Image: Panel D). Sensory Neuroscience Honours Students Mr Wilfred Angkawijawa Mr Jibriil Ibrahim Ms Rushita Kalidindi Mr Michael Nguyen Ms Anabella Reaper Mr Victor Suturin Research Officers Dr Vladimir Dubaj Dr Saman Haghgooie Dr Chun Wang Visiting Scientists Prof Gunter Ehret Prof Peter Thorne Research Assistants Mr Justin Bourke Ms Kahli Cassells PhD Students Ms Emma Brunton Ms Duwage Dasuni Alwis Ms Collette Mann Mr Nathan Smith www.med.monash.edu.au/physiology/research/smoothmuscle/index.html 66 Dr Nicholas Price Associate Professor Ramesh Rajan We examine different aspects of sensory processing in the brain using animal and human models. NHMRC Project Grant We record electrical signals of nerve cells in animal models to examine what happens to the brain’s sensory areas when there is traumatic brain injury as occurs following car or sporting accidents. We have shown that brain injury causes specific brain sensory processing deficits, which could explain why affected individuals have cognitive and movement problems. ARC Special Research Initiative Grant (Research in Bionic Vision Science and Technology) • Physiological bases of audiovisual integration, Rosa/Rajan (2009–2011). • Direct stimulation of the visual cortex: A flexible strategy for restoring high-acuity pattern vision, Lowery/Rosa/ Rosenfeld/Rajan (2010–2013). In human models we study how the brain extracts information from 'noise', in both normally developing people and those with Autism spectrum disorders. We showed that time of language acquisition impacts on academic performance and how developmental setbacks can be overcome. Our findings will impact on the design of assessments for diverse student populations in tertiary institutions. We have also linked speech processing difficulties in high-functioning autistic people to hearing problems. We continue to participate in the Monash Vision Group, a University initiative focussed on developing bionic technologies to restore vision in blind patients. Currently, we are testing in animal models the first prototypes of a 'bionic eye' based on direct stimulation of the cerebral cortex. www.med.monash.edu.au/physiology/staff/rajan.html 67 Annual Report 2011 Reproductive Neuroendocrinology Dr Jeremy T Smith We study the mechanisms and pathways within the brain that control fertility. Our group is also aiming to develop new strategies for the treatment of infertility. Research Fellow Dr Qun Li (33%) Research Assistants Ms Alda Pereira (50%) Ms Alix Rao (50%) Ms Sophie Saleh (50%) Honours Student Ms Julie-Ann De Bond Reproduction is complex process, which is controlled by three key ‘players’: the brain, pituitary gland and testis or ovaries. At the top of this hierarchical regulatory system is gonadotrophin-releasing hormone (GnRH), which is produced and secreted from the preoptic area of the brain. This molecule is a chemical master switch that triggers the onset of puberty and regulates key reproductive hormones: luteinising hormone and follicle stimulating hormone. These hormones (also called gonadotrophins) circulate in the peripheral blood to stimulate the gonads (testis or ovaries). The precise mechanisms that control GnRH secretion were, until recently, unknown. We have demonstrated that a novel protein in the brain, Kisspeptin, is a critical regulator of GnRH, the gonadotrophins and fertility. NHMRC Project Grant • Kisspeptin and its receptor mastermind reproduction (2010–2012). ARC Future Fellowship • Masterminding reproduction: Kisspeptin and RFamide-related peptide (2009–2013). Monash Researcher Accelerator Program • (2011–2012) Kisspeptin neurons (red) and neurons labelled with a neuronal tracer dye (BDA, green) in the arcuate nucleus of the brain. Insert shows a higher magnification image of kisspeptin, GnRH (blue) and BDA labelled neuronal terminals in the exterior zone of the median eminence ‘on route’ to the pituitary gland. Awards and Achievements Dr Smith • Joint winner of the 2011 Newcastle Reproduction Emerging Research Leader Award, Society for Reproductive Biology. Behavioural Neuroendocrinology Research Assistant Ms Sara Drew PhD Students Ms Joanna Engle Mr Adam Morrissey Mr Cameron Ralph Ms Bronwyn Stevens We investigate how stress impacts body function and behaviour in animals and humans, and the effect of environmental factors on milk production in goats and sheep. NHMRC Project Grant In collaboration with researchers at the University of Michigan, in the US, we have shown that social stress suppresses the secretion of reproductive hormones and sexual behaviour in sheep. We have also established that the stress hormone cortisol plays an important role, where it acts both within the brain, and externally, in the pituitary gland. In collaboration with researchers at the University of Melbourne, we have discovered that the amount of cortisol in blood does not reflect its actual concentration in cells. • Dissecting the impact of stress on reproduction: Novel peptide mediates the inhibitory effects of stress on female reproduction, Tilbrook/Clarke/Hemsworth (2009–2011). In addition, we have shown the amount of fat on animals affects how they respond to stress. Higher stress responses occur in obese animals. Australian Pork Limited Project Grant We have shown that daylight affects milk production in goats and sheep. As a result, we are developing approaches to improve milk production. We have also identified factors that affect animal welfare and are developing recommendations to improve the wellbeing of pigs and laying hens. From a human perspective, we are collaborating with researchers at the Baker IDI Heart and Diabetes Institute and Monash Alfred Psychiatry Research Centre, exploring the effect of stress on mental illness and metabolic syndrome. We have shown how stress affects patients with major depression who are taking antidepressants. 68 Professor Alan Tilbrook • Gonadotropin inhibitory hormone, Clarke/Tilbrook (2009–2011). Australian Research Council Discovery Grant Rural Industry Research and Development Corporation Project Grant • Improving milk yield in dairy sheep, Tilbrook/Cameron/ Dunshae/Leury (2009–2012). • Usefulness of preference for resources and biological functioning to assess animal welfare, Tilbrook/ Hemsworth (2010–2013). Australian Pork Limited Project Grant • Effects of aggressive characteristics of individual sow and mixing strategies on the productivity and welfare of group-housed gestating sows Hemsworth/Tilbrook (2010–2012). Australian Egg Corporation Limited Project Grant • The effects of time off food and water on the welfare of spent laying hens, Tilbrook/Hemsworth (2010–2011). Obesity In 2007/2008, 61% of the Australian population were overweight or obese.* >> How does the brain regulate food intake, energy use and body weight? >> How does early-life nutrition affect weight regulation throughout life? >> How is fat metabolism regulated in fat and muscle? >> How is obesity linked to type 2 diabetes? *Australian Bureau of Statistics 2008, National Health Survey 2007-2008 Annual Report 2011 Obesity Neuronal Metabolism and Degeneration We study how the brain regulates appetite, body weight and glucose balance during different metabolic states and in response to various hormones. We are interested in how high fat or calorie restriction diets affect how the brain regulates energy metabolism. Research Assistants Ms Debbie Arena Ms Moyra Lemus Mr Alex Reichenbach PhD Student Ms Dana Briggs Honours Student Ms Jacqueline Bayliss We showed for the first time that the brain becomes resistant to the effects of ghrelin, a metabolic hormone that stimulates appetite, during diet-induced obesity. A select group of nerve cells in the brain called NPY cells stop responding to ghrelin so ghrelin no longer increases food intake. In the context of obesity, we believe the brain no longer processes the basic ‘need to eat’ function, as the body has sufficient energy stores. Excessive eating during diet-induced obesity is most likely controlled by the rewarding properties of food and food cravings. Dr Zane Andrews Metabolic Neuroendocrinology We aim to discover novel ways of altering energy expenditure to prevent or treat obesity. ARC Future Fellowship • How appetite-suppressing brain cells maintain normal function and prevent the development of obesity (2011–2014). We focus on understanding how the body expends energy. We are particularly interested in the process of thermogenesis, a form of cellular heat production. Awards and Achievements Dr Andrews • Organising chair: ESA Neuroendocrinology Australasia symposium. • Monash Researcher Accelerator Program. Research Assistant Ms Elaine Chase PhD Students Mr Scott Clarke Dr Kevin Lee Honours Students Mr Demunu Sakda Galamulage Mr Jared Mamrot Our observations have significant implications for body weight control as diet-induced weight loss would gradually restore ghrelin’s ability to increase appetite. This makes it difficult for most people to maintain a lower body weight after diet-induced weight loss. Dr Belinda Henry Thermogenesis occurs in specialised tissues in the body including brown fat and skeletal muscle. We have shown that a lower rate of thermogenesis may lead to an increased susceptibility to weight gain and obesity. We study the cellular and molecular mechanisms that underpin thermogenesis and hope to identify candidate targets for new anti-obesity therapies. NHMRC Project Grant Do you feel hot and sleepy after lunch? Skeletal muscle heat production increases in response to eating. This is a novel means by which the body expends energy. The grey box illustrates meal time. • Skeletal muscle thermogenesis in models of predisposition to obesity, Henry/Clarke/Andrews (2011–2013). Awards and Achievements Dr Henry • Councillor, Endocrine Society of Australia. • Program organising chair for the Endocrine Society of Australia, Basic Science Weekend. NHMRC Project Grants • Our paper, published in Endocrinology, was selected as Editor’s choice in July 2011. Henry BA et al., Central leptin activates mitochondrial function and increases heat production in skeletal muscle. Endocrinology, 2011. 152: 2609-2618. • Diet-induced obesity causes ghrelin resistance, Andrews/ Spencer (2011–2013). • Physical exercise restores energy homeostasis in obesity through hypothalamic neurogenesis, Watt/Andrews/ Oldfield (2011–2013). • Skeletal muscle thermogenesis in models of predispostion to obesity, Henry/Clarke/Andrews (2011–2013). www.med.monash.edu.au/physiology/staff/henry.html Ghrelin activates appetite-induced NPY brain cells (green, top panel) and Fos protein (red, centre panel). Co-expression of Fos and NPY neurons after ghrelin treatment (bottom panel) illustrates that ghrelin activates NPY neurons. • Ghrelin-induced neuroprotection is mediated by AMPK (2009–2011). Metabolic Neuroscience Laboratory Professor Brian OIdfield www.med.monash.edu.au/physiology/staff/andrews.html Professor Michael Cowley Director, Monash Obesity and Diabetes Institute Metabolic Neurophysiology Research Fellows Dr Pablo Enriori Dr Maria Cecilia Garcia-Rudaz Dr Sara Litwak Research Assistant Ms Joanne Pagnon PhD Student Ms Stephanie Simonds Project Officer Dr Daphne Vogiagis Honours Students Mr Weiyi Chen Ms Jenny Wilson We are mapping the pathways in the brain that sense stored fat, stomach contents and blood sugar. Our aim is to understand how information is relayed throughout the brain to balance energy intake and use, and to control body weight. NHMRC Project Grants We are particularly interested in obesity, diabetes and metabolic disease. Recently, there has been a dramatic worldwide increase in the incidence of these conditions. In Australia, over 13 million people are overweight or obese and almost one million people have diabetes. Pfizer Australia Senior Research Fellowship Specifically, we focus on how signals from the body, such as leptin, lose the ability to control weight once a person becomes obese. We seek to understand how and why the brain becomes resistant to sensing information that would otherwise convey that the body has sufficient stores of energy. We have recently discovered that nerve cells in the brain called POMC neurons detect blood sugar levels and also regulate metabolism. In addition, we have made progress in understanding how certain hormones regulate glucose production and uptake, independent of insulin. We have also applied for a patent based on these methods of regulating blood glucose levels. • The role of brain inflammation in leptin resistance, Cowley (2011–2014). • Does loss of melanocortin glucose sensing contribute to diet induced diabetes? Cowley/Enriori/Tiganis (2010–2013). • Re-establishing glucose sensing in α-MSH cells to treat diabetes, Cowley (2009–2014). Research Fellows Dr Juliane Kampe Dr Aneta Stefanidis Dr Aaron Verty Research Assistant Ms Erika Ortiz PhD Students • Does leptin cause hypertension? Cowley/Brown (2010–2012). Ms Elaine Adler Ms Sarah Haas Lockie Ms Nilanka Hertioga Dr Cathy Jensen (completed August 2011) Awards and Achievements Masters Student Heart Research Foundation Project Grant Professor Cowley • Toured Australia during National Science Week. He visited major and regional centres, where he gave interviews and presentations about his research. • Elected Fellow of the Australian Academy of Technological Sciences and Engineering. Mr Neil Forrest This group aims to understand the role of the brain in controlling food intake and the burning of energy, which ultimately lead to changes in body weight and possibly obesity. Awards and Achievements Recently, a number of pharmaceutical treatments have been withdrawn because of adverse side effects, which limits the options available to overweight or obese individuals. Furthermore, there are no effective drugs for extreme (morbid) obesity other than lap band and gastric bypass surgery. Dr Aneta Stefanidis • Recipient of a 2011 MODI travel grant. Ms Haas Lockie • Recipient of the inaugural Anthony Koelmeyer International PhD Excellence award. Our laboratory studies the mechanisms that the brain uses to reduce hunger in certain forms of bariatric surgery and how it curbs hunger and possibly increases energy expenditure We hope to explain the brain mechanisms underlying the efficacy of surgeries such as the adjustable gastric band, which will in turn help to identify targets in the brain for antiobesity therapies. NHMRC Fellowship • Professor Oldfield (2006-2011). NHMRC Project Grants • The differential innervation of fat – potential to target visceral adiposity, Oldfield/Clarke (2011–2013). Neurons in the hypothalamus (green) surrounded by orexin containing nerve fibres (red), part of the neural circuitry in the brain controlling hunger. • Physical activity restores energy homeostasis in obesity through hypothalamic neurogenesis, Watt/Andrews/ Zane/Oldfield (2011–2013). ARC Linkage Grant • Use of an animal model to understand mechanisms underlying reductions in body weight associated with the use of the laparoscopic adjustable gastric band, Oldfield/ Dixon/Raven (2010–2012). www.med.monash.edu.au/physiology/staff/oldfield.html 72 www.med.monash.edu.au/phusiology/staff/cowley.html 73 Annual Report 2011 Perinatal Programming of Stress and Metabolism Research Assistants Ms Lauren Bulfin Ms Melanie Clarke Dr Sarah J. Spencer We are investigating the long-term metabolic, neuroendocrine and behavioural effects of overfeeding during early life; the mechanisms by which this can program obesity; and how perinatal overfeeding can affect an individual’s ability to combat psychological stress and infections. We have shown that neonatally overfed animals become overweight during infancy and remain obese into adulthood. We have also seen that these neonatally overfed animals have exaggerated responses to psychological stress and to an immune challenge. Our research helps explain how early life overfeeding can program these responses. Our work has important health implications for obese individuals trying to overcome stress and improve immune responses. The early life environment is crucial in establishing an animal’s long-term physiology. As such, over- or under-nutrition in infancy can significantly affect the ability to regulate metabolism and body weight throughout life. NHMRC Peter Doherty Postdoctoral Fellowship We are therefore investigating: • How early life nutrition programs the brain to regulate weight; and • What are the long-term metabolic, neuroendocrine, and behavioural effects of early nutrition on the stress and immune systems? • Neuroendocrine mechanisms for stress hyporesponsiveness in lactating females (2007-2011). NHMRC Project Grant • Diet-induced obesity causes ghrelin resistance, Andrews/ Spencer (2011-2013). Australia Research Council Discovery Project Grant • Early life overfeeding: Mechanisms for programming obesity and long-term immune dysfunction (2010-2012). Monash Research Accelerator Program Award • (2011–2012) www.med.monash.edu.au/physiology/staff/spencer.html Biology of Lipid Metabolism This group is working to develop preventative strategies to overcome obesity, while also investigating the link between obesity and type 2 diabetes. Postdoctoral Fellows Dr Andrew Hoy Dr Ruth Meex Dr Romana Stark Research Assistants Ms Emma Brunton Ms Maria Matzaris Ms Joanne Pagnon PhD Students Mr James Boon Ms Melissa Borg Ms Vanessa Haynes Ms Rachael Mason Honours Student Ms Alice Barnett Associate Professor Matthew Watt Monash Fellowship • Arresting the obesity epidemic: Molecular and cell biology of lipid metabolism in chronic metabolic disease, Watt (2008–2012). Obesity is a serious medical condition that has doubled in prevalence over the past 20 years, and affects one in every three Australian adults. We study the molecular and cellular regulation of fat metabolism in fat and skeletal muscle, and how defects in fat metabolism lead to insulin resistance, a precursor to type 2 diabetes. We aim to influence the development of preventative and therapeutic strategies for obesity and related disorders. NHMRC Senior Research Fellowship • Associate Professor Watt (2010-2014). NMHRC Project Grants • Physical activity restores energy homeostasis in obesity through hypothalamic, Watt/Andrews/Oldfield (2011–2013). • Regulation of insulin sensitivity by reactive oxygen species, Tiganis/Watt (2010–2012). • Identifying a novel role for pigment epithelium-derived factor in obesity-related metabolic dysfunction, Watt (2010–2012). • Circulating ceramides, inflammation and insulin resistance, Watt (2009–2011). Image showing lipid droplets containing fat (red) in an adipocyte (fat cell). The protein adipose triglyceride lipase (green), which breaks down fat is also shown. Image: Joanne Pagnon. ARC Discovery Project Grant • Regulation of lipolysis: New players, new paradigms (2009-2011). www.med.monash.edu.au/physiology/research/bolm.html 74 Structural Biology Understanding the molecular basis of biology and disease >> Infection >> Immunity >> Malaria >> Anti-cancer agents >> Alzheimer’s disease >> Huntington’s disease >> Cardiovascular disease >> HIV >> Virus biology >> Toxin biology >> Developmental biology >> RNA biology >> Bioinformatics Structural biology also plays a central role in the design of therapeutic drugs and novel vaccines, and tools for biomedical applications. A molecular model of a non-fluorescent GFP-like protein isolated from a marine coral. This cut-away representation of the 11 stranded ß–barrel reveals the protected light absorbing chromophore, with water molecules (green spheres) and surfaces (mesh). Image: Jion Battad. Annual Report 2011 Structural Biology Pepidomimetic Drug Design and Membrane Nanotechnology Our group focuses on peptide-based drug design and biomembrane nanotechnology. Research Fellows Dr Mark Del Borgo Dr John Lee Research Assistant Ms Sharon Unabia PhD Students Ms Romila Devi-Gopalan Ms Ann Du Mr Daniel Hirst Mr John Paul Juliano Ms Jia Li Zhai In collaboration with Professor Patrick Perlmutter (School of Chemistry), we are developing novel compounds that allow us to exploit the potential of peptides as drugs. We are currently applying our technology to develop cancer vaccines (with Associate Professor Tony Purcell, University of Melbourne), new treatments for cardiovascular disease (with Professor Rob Widdop and Dr Emma Jones, Department of Pharmacology) and inhibitors of HIV budding (with Dr Miranda Shehu-Xhilaga and Associate Professor Gilda Tachedjian, Burnet Institute). Viral Immune Evasion Laboratory Professor Mibel Aguilar Associate Dean (Research Degrees) ARC Discovery Grant • The mechanism of membrane disruption by antimicrobial peptides, Aguilar/Separovic/Mark (2011–2013). • The design and synthesis of inhibitors of HIV budding, Aguilar/Shehu-Xhilaga, (2010–2012). National Heart Foundation • PIPS regulate G protein-coupled receptors, Aguilar/Thomas (2011-2012). Mason Foundation Research Assistant • Identification of new drugs to treat Alzheimer's disease, Aguilar/Small/Perlmutter (2011). PhD Student Mr Luke Cossins Ms Leigh Yang Our membrane nanotechnology projects include: new methods for membrane protein purification and analysis for Alzheimer’s disease (with Professor David Small, Menzies Research Institute), G protein-coupled receptor function (with Professor Wally Thomas, University of Queensland), antimicrobial peptide function (with Professor Frances Separovic, University of Melbourne) and new biosensor devices (with Farfield Scientific). Dr Natalie Borg We study the role of proteins involved in viral immunity and evasion to understand viral disease. ARC Discovery Project Grant Our protein targets come from a growing family of enzymes that regulate almost all cellular processes. The enzymes, called E3 ligases, literally add molecular tags to other proteins, modifying the tagged protein’s function. Viruses can use these mechanisms to their advantage to manipulate the immune system and avoid detection. • (2008–2011) Our ultimate aim is to decipher the role of these proteins in the cell. This information could be exploited to design novel treatments to enhance immunity against persistent or virulent infections such as influenza, and to design anti-viral therapeutics. As these proteins are too small to see with a microscope, we use X-ray crystallography, biophysical approaches and cellular assays to gain information about the molecular shape and function of these molecules and their binding partners. • (2011–2013) NHMRC Career Development Award A molecular tag that is added to target proteins to modify their function. www.med.monash.edu.au/biochem/staff/borg.html NHMRC Project Grants • Elucidating the mechanism of action of dendrimer nanoparticles against HIV, Tachedjian/Gorry/Ramslund/ Aguilar (2011–2013). • The receptor-associated protein (RAP) as a molecular chaperone for the amyloid protein (Abeta) of Alzheimer's disease, Small/Aguilar/Shepherd/Strickland (2010–2012). • The role of transthyretin in familial amyloidotic polyneuropathy, Small/Parkington/Chung/Aguilar/ Coleman (2009–2011). Protein Misfolding Laboratory Schematic showing how the structure of a biological membrane can be studied by a new type of biosensor that measures the changes in packing, alignment and degree of order of lipid molecules assembled in the bilayer. www.med.monash.edu.au/biochem/research/projects/peptide.html Research Fellows Structural Microbiology Research Fellows Dr Natasha Ng Dr Andrew Sivakumaran Dr Trifina Sofian Research Assistant Ms Sally Troy PhD Student Mr Adam Shahine Honours Student Ms Li Lynn Tan Associate Professor Travis Beddoe Dr Victoria Hughes Dr Mary Pearce Dr Noelene Quinsey Dr Amy Robertson We study virulence factors from pathogenic microbes using X-ray crystallography. Pfizer Australia Research Fellowship Pathogenic bacteria use surface and secreted proteins to cause infection and/or evade the immune system. These proteins have varied functions: they stick to cells, produce toxins and manipulate both host immune responses and cellular function. Awards and Achievements Ms Weiwen Dai Mr Nik Sotirellis Dr Travis Beddoe • Finalist, Eureka Prize for Infectious Diseases Research. PhD Students • (2010–2014) We use a combination of biochemistry, biophysical and X-ray crystallography approaches to determine the molecular role of these infectious proteins. This will not only unravel key aspects of microbial pathology, but will also provide a range of novel antimicrobial drug targets. Research Assistants Ms SHani Keleher Ms Anja Knaupp Ms Miranda Wills Ms Li Yang Ms Evelyn Yip Masters Student Mr Christopher Lupton Honours Students Mr Joybrata Banerjee Mr Jeremy Nagel In future studies, we will scour bacterial genomic databases for unknown proteins that may play a role in bacterial physiology and pathogenesis. Professor Stephen Bottomley We study how proteins fold to their correct shape, what happens when this goes wrong and develop therapeutic approaches for a range of devastating diseases such as Huntington’s disease and emphysema. NHMRC Project Grant For a protein to function it has to fold into its correct shape. However, this reaction is complex and can go wrong. A large number of disorders, including Alzheimer’s and Huntington’s diseases are caused by a failure of a specific protein to fold correctly. We use a range of technologies, including protein engineering, biological spectroscopy, structural biology and cellular approaches to understand how proteins fold and misfold. • Analysing the detrimental effects of polyglutamine expansion, Bottomley/Devlin (2010–2012). • To investigate how the aggregation of proteins during neuronal injury promotes neurotoxic plasmin formation, Medcalf/Bottomley/Samson (2010–2012). ARC Discovery Grant From our research studies, we have characterised proteins which bind to and stabilise misfolding proteins. Specifically, we identified a cellular chaperone molecule that binds to ataxin-3 and prevents its misfolding. Aggregation of ataxin-3 causes Machado Joseph disease, a neurodegenerative disorder which affects indigenous Australians in the Northern Territory. We are exploring treatment approaches for this disease. NHMRC Senior Research Fellowship • Stephen Bottomley (2007–2011). NHMRC Program Grant • Control of proteases in infectious, degenerative and cardiovascular disease, Whisstock/Bird/Buckle/ Bottomley/Pike/Smith (2008–2012). We discovered that the interaction between Ataxin-3 and the chaperone αB-crystallin prevents ataxin-3 aggregation. We then used Nuclear Magnetic Resonance to identify which regions of Ataxin-3 (coloured) interact with αB-crystallin. NHMRC Project Grants • Structure and functional characterisation of AB5 toxins (2011–2013). www.med.monash.edu.au/biochem/staff/bottomley.html • Cytokine structure and mechanisms of a superagonist antibody (2011–2013). ARC Discovery Grant • Evolution of AB5 toxins (2010–2012). The crystal structure of a bacterial virulence factor with its bound substrate. (Vivian et al., Structure, 2010). www.med.monash.edu/biochem/staff/beddoe.html 78 79 Annual Report 2011 Structural Biology Protein Structure, Dynamics and Bioinformatics Research Fellows Dr David Hoke Dr Itamar Kass Dr Grischa Meyer Software Developers/ Bioinformaticians Mr Steve Androulakis Mr Mark Bate PhD Students Mr Daniel Andrews (with Dr Anna Roujeinikova) Mr Yasir Arafat Ms Olga Ilyichova Ms Bindu Jayakrishnan Dr Fasséli Coulibaly NHMRC Career Development Award • (2007–2011) We study the infectious cycle of viruses at a molecular level to understand their assembly, evolution and virulence. NHMRC Program Grant We work on the following projects: • Control of proteases in infectious, degenerative and cardiovascular disease (2008–2012). Structural analysis of early steps in poxvirus assembly • Understanding the assembly of poxvirus particles (2010–2012). We aim to understand how the structure and dynamics of proteins dictates their function. NHMRC Senior Research Fellowship Currently, we study the role of proteases in human health and disease. We use a combination of crystallography and computational techniques to design inhibitors of human Kallikrein-4, human aminopeptidases, and active/inactive proteases from the scabies mite. We also use X-ray crystallography, Surface Plasmon Resonance Imaging and biochemical techniques to study the interaction between the Type 1 diabetes autoantigen Glutamic Acid Decarboxylase (GAD65) and autoantibodies. Research Fellows Dr Marcel Hijnen Dr John Martyn Research Assistant In collaboration with the Monash eResearch Centre and the Australian Synchrotron, we use X-ray crystallography and computer science approaches to create new tools for protein structure determination. Recently, we developed a new online data management program called TARDIS, the world’s first repository for raw X-ray diffraction data. We also develop and host a range of bioinformatics resources. Using molecular dynamics simulations, we aim to understand the role of conformational change and flexibility in protein function. We require high performance supercomputers for this task, and use the Monash Sun Grid and Orchard, an 800-core Apple supercomputing cluster at Monash, as well as the Victorian Life Sciences Computation Initiative. We collaborate with scientists university-wide, nationally and internationally. Ms Cathy Accurso PhD Student Ms Suzan Cingi Poxviruses are among the largest viruses infecting humans and have a complex assembly involving multiple steps of maturation. We generate 3-dimensional crystal structures of key proteins to investigate the molecular details of these assembly processes. • Structural analysis of poxvirus assembly (2009–2012). NHMRC Project Grants • Structure and function of the HCV glycoproteins (2010–2012). ARC Discovery Project Grant • Microcrystallography of spheroids: crystalline armours of insect viruses (2010-2012). Microcrystallography CASS Foundation We use X-ray microcrystallography to analyse tiny viruscontaining crystals, which are produced by insect viruses. These crystals function as armours for virus particles so that viruses can survive for decades in the environment. • Micro Cubes as a vaccine against HIV (2011). Novel vaccine delivery approaches Crystals formed in vivo by insect viruses have remarkable robustness and packaging ability. We are interested in exploiting these features to engineer microparticles as a potential HIV vaccine candidate. Bill and Melinda Gates Foundation, Grand Challenges Explorations Grant • Micro Cubes as a vaccine for the developing world (2011-2012). Awards and Achievements Dr Coulibaly • Accepted into Monash Research Accelerator program (2010–2011). Conformational flexibility of a peptide (blue) bound to the Major Histocompatibility Complex revealed by Molecular Dynamics simulations taken every 10 nanoseconds. The peptide conformation in the crystal structure is shown in yellow. Structure of the three classes of viral crystalline armours produced by RNA and DNA viruses. www.med.monash.edu.au/biochem/staff/abuckle.html Structural Immunology Structural Virology Associate Professor Ashley Buckle Dr Craig Clements www.med.monash.edu.au/biochem/staff/coulibaly.html We investigate the interaction between molecules of the immune system. The innate immune system is the first line of defence against invading pathogens. Receptors on immune cells called Natural Killer cells can distinguish between ‘self’ and ‘non-self’ molecules presented by the body. This ability to identify cells containing ‘non-self’ material ultimately leads to the destruction of infected cells, and also plays a role in the body’s response to cancerous cells. Research Assistant Ms Maya Olshina PhD Students Mr Nicholas Walpole Mr Li Zeng We use a combination of structural biology and biophysical techniques to determine what features are important for the Natural Killer cell to ‘see’ an infected cell. We gain a greater understanding of the immune response to infection and cancer, which may help in the design of better therapeutics. ARC Discovery Project Grant, including Queen Elizabeth II Fellowship • Investigation of the fundamental roles of class Ib MHC molecules in immunity (2007-2011). 80 Comparison of the binding of three different peptides to HLA-G. (Walpole et al., Journal of Molecular Biology, 2010. 397: 467-480). 81 Annual Report 2011 Structural Biology Toxin Biology Laboratory Dr Michelle Dunstone Fluorescent Proteins and their Applications We study the function of toxins used by pathogens and the human immune system. We study the properties of GFP-like proteins and develop novel optical tools for biomedical applications. Pore forming toxins are proteins commonly identified as bacterial virulence factors, proteins of the immune system and animal venoms. These molecules are able to change shape from water soluble single proteins to lipid membrane inserted rings. These rings act as holes in the target cell membrane that can result in cell death by forming holes in the cell or by allowing other toxins to invade. Research Fellow NHMRC Career Development Award Research Assistants • The role of Membrane Attack Complex/Perforin-like pore forming proteins in disease and immunity (2010–2014). Dr Tamas Hatfaludi Ms Bethany Crane Ms Sue Ekkel PhD Student Ms Stephanie Kondos CASS Foundation Science and Medicine Grant Mr Jion Battad Mr Alexander May Mr Craig Don Paul Naturally occurring and engineered members of the GFPsuperfamily collectively have an extraordinary range of properties. In particular we are interested in how the structure of these proteins gives rise to their optical properties. We use this knowledge to design and engineer new proteins and biosensors for investigating the organisation of molecular networks in living cells. In addition to fluorescent probes for monitoring events in live cells, we also develop optogenetic tools that when illuminated allow the control of specific cellular pathways. Honours Student NHMRC Program Grant Research Assistant • Intracellular survival of Burkholderia pseudomallei and evasion of autophagy, Boyce/Devenish/Prescott (2009–2012). PhD Students ARC Discovery Project • Structural and functional studies on Membrane Attack Complex/Perforin-like proteins (2009–2011). Dr Mark Prescott Ms Giuseppe Lucarelli Model of a MACPF pore in a cell membrane. Modelled by Dr Michael Kuiper, Victorian partnership for advanced computing. • Structural characterisation of a novel and potent anti-inflammatory protein (2011). Ms Julia McCoy A molecular model of a non-fluorescent GFP-like protein isolated from a marine coral. This cut-away representation of the 11 stranded ß–barrel reveals the protected light absorbing chromophore, with water molecules (green spheres) and surfaces (mesh). Image: Jion Battad. Monash Research Accelerator Program • The study of MACPF pore structure and their function in bacteria (2011–2012). www.med.monash.edu.au/biochem/staff/prescott.html www.med.monash.edu.au/biochem/staff/dunstone.html Macromolecular Structure and Interactions in Cellular Function Structural Biology of Proteases and their Inhibitors We study the molecular basis of macromolecular interactions that occur in human cells: gene expression, cell growth and proliferation, and cellular immunity. Dr Sheena McGowan We are particularly interested in protein-oligonucleotide systems. These include proteins which bind to mRNA to regulate translation and proteins that recognise viral RNA and initiate immune responses to viral infections. We also design and test new antibiotics against bacterial pathogens and peptide-based inhibitors of cancer cell proliferation and migration. We characterise novel malarial drug targets and use this knowledge to design new anti-malarial therapies. Research Assistants Ms Kitmun Huynh Ms Komagal Sivaraman Due to the rapid spread of drug resistance in the malaria parasite there is an urgent need for new treatment options. The action of two neutral metalloaminopeptidases, M1 alanyl aminopeptidase and M17 leucyl aminopeptidase, are essential to the parasite's growth and development. Blocking the activity of these molecules is an effective disease prevention strategy. We use techniques in X-ray crystallography, biochemistry and biophysics to characterise these enzymes. This information is then used to develop compounds with potential applications in human medicine. NHMRC Senior Research Fellowship • Professor Wilce, Protein-RNA interactions (2007-2011). Associate Professor Jackie Wilce Professor Matthew Wilce NHMRC Project Grants • Characterisation of the growth receptor bound 7 (Grb7) protein and protein and RNA partners involved in the regulation of stress granule formation and cell migration (2011-2013). • Protein recognition of small RNAs in innate immunity (2011-2013). • Structural and functional role of HIV-1 gp41 terminal interactions in the membrane fusion mechanism (2009-2011). ARC Discovery Grants • Specificity and architecture of protein-mRNA interactions regulating gene expression (2011-2013). • Optimisation of peptidic non-phosphorylated inhibitors of the Grb7 SH2 domain (2009-2011). NHMRC Project Grant • Plasmodium falciparum neutral aminopeptidases: Structure-function analysis for the discovery of anti-malarial drugs (2009–2011). Research Fellows ARC Future Fellowship • (2010–2014) Monash Research Accelerator Program • (2011–2012) The X-ray crystal structure of the Plasmodium falciparum M17 aminopeptidase (McGowan et al., Proceedings of the National Academy of Sciences, USA, 2010. 107(6): 2449-2454). Dr Simone Beckman Dr Menachem Gunzburg Dr Zhihe Kuang Dr Reece Lim Dr Nicole Pendini PhD Students www.med.monash.edu.au/biochem/staff/mcgowan.html Mr Nigus Ambaye Mr Chris Szeto Ms MinYin Yap Masters Student Crystal structure reveals the binding mode of a peptide inhibitor of Grb7 that is involved in cancer cell migration and proliferation. Mr Yano Yoga http://research.med.monash.edu.au/wilce 82 83 Annual Report 2011 Structural Biology Protein Crystallography Unit Professor Jamie Rossjohn We study molecular interactions central to infection and immunity. The group uses structural biology, including synchrotron radiation, and biophysical approaches as the main research tools. Awards and Achievements • Awarded Roche Organ Transplantation Research Foundation Recognition Prize jointly with Professor McCluskey. Ms Margaret Bills Dr Jennifer Huynh Our research allows us to understand host recognition and pathogen responses. We collaborate with scientists throughout Australia and internationally and are supported by funding from the ARC, NHMRC, Anti-Cancer Council, NIH and Monash University. The laboratory is also an integral part of the ARC Centre of Excellence in Structural and Functional Microbial Genomics. Research Fellows NHMRC Project Grant • Mallevaey et al., A molecular basis for NKT cell autoreactivity and recognition of CD1d-self antigen. Immunity, 2011. 34: 315-326. • A structural investigation into the adaptive immune response to a persistent and ubiquitous human virus, Rossjohn/Purcell (2011–2013). • Wun et al., A molecular basis for the exquisite CD1drestricted Ag-specificity and functional responses of NKT cells. Immunity, 2011. 34: 327-339. NHMRC Program Grant • Uldrich et al., A semi-invariant Vα10(+) T cell antigen receptor defines a population of natural killer T cells with distinct glycolipid antigen-recognition properties. Nat Immunology, 2011. 12: 616-23. Administration Dr Sara Baratchi Dr Richard Berry Dr Mugdha Bhati Ms Renee Duncan Dr Stephanie Gras Dr Dene Littler Dr Thao Nguyen Dr Jerome Le Nours Dr Onisha Patel Dr Jan Petersen Dr Hugh Reid Dr Alex Theodossis Dr Kelly-Anne Twist Dr Julian Vivian Dr Neal Williams Dr Pascal Wilmann Research Assistants Mr Andrew Gibb Mr Ray Koh Ms Kylie Loh Ms Halim Noor Ms Maria Sandoval Ms Christina Wang PhD Students Mr Andrew Clarke Mr John Liu Ms Melissa McKnight Mr Stephen Scally Mr Adam Shahine Mr Nick Walpole Mr Li Zeng Honours Student Ms Amelia Aslanides Mr Simon Giang Ms Sofia Mahood-Ul-Hassen Ms Li Lynn Tan • Antigen presentation, recognition and the immune response, McCluskey/Heath/Carbone/Brooks/Rossjohn/ Shortman (2007v2011 and 2012–2016). NHMRC Australia Fellow • Australian Fellowship, Rossjohn (2011–2016). ARC Federation Fellow • An investigation into Infection, Immunity and Rational Drug Design, Rossjohn (2006–2011). ARC Discovery Grants • A structural and functional investigation into events within the immunological synapse, Rossjohn/McCluskey (2011–2013). • A structural investigation into the peptide loading complex molecular machine, Rossjohn (2008–2012). Infection, Immunology and Developmental Biology Professor Rossjohn • Finalist, Eureka Prize for Infectious Diseases Research, jointly with Associate Professor Beddoe and Professor Paton. • Top ranked 2011 NHMRC program grant. • Awarded NHMRC Australia Fellowship. • Pellicci et al., Recognition of β-linked self glycolipids mediated by natural killer T cell antigen receptors. Nature Immunology, 2011. Jul 31; 12(9):827-833. • Vivian et al., Killer Immunoglobulin Receptor 3DL1mediated recognition of Human Leukocyte Antigen B. Nature, 2011. Oct 23: doi: 10.1038/nature10517. [Epub ahead of print]. Mr Andrew Clarke • Recipient of the inaugural Anthony Koelmeyer International PhD Excellence award. Research Fellows Dr Tamas Hatfaludi Dr Anabel Herr Dr Hilary Hoare Dr Travis Johnson Dr Ruby Law Dr Isabelle Lucet Dr Siew Siew Pang Dr Andrew Perry Dr Corrine Porter Dr Carlos Rosado Dr Jiangning Song Dr Dr Daouda Traore Dr Mark Walter Research Assistants Ms Gilu Abraham (with Dr Lucet) Ms Rebecca Bamert (with Dr Lucet) Mrs Tanya BashtannykPuhalovich Ms Devadharshini Jeevarajah Mr Gordon Lloyd Mr Adam Quek (with Dr Law) Ms Qingwei Zhang PhD Students Ms Michelle Bennett Ms Susie Berkowicz Ms Tova Crossman Ms Aminah Giousoh Mr Trevor Key Ms Stephanie Kondos Mr Chris Langendorf Mr Khalid Mahmood Mr Cyril Reboul ARC Centre of Excellence • Structural and functional genomics, Adler/Rood/Coppel/ Davies/Rossjohn/Whisstock/Nagley/Devenish/ Hertzog/ Meussen/Smith (2006–2013). ARC LIEF Grant • An advanced flow cytometry facility for the Peter Doherty Institute, Carbone/Heath/Kent/Purcell/Rossjohn/Godfrey (2011). Professor James Whisstock We focus on understanding the structure, function and biology of proteins involved in infection, cancer immunology and developmental biology. ARC Centre of Excellence in Structural and Functional Microbial Genomics We are particularly interested in how pore forming Membrane Attack Complex/Perforin-like (MACPF) proteins eliminate virally infected and pre-cancerous cells. We also study the role of cholesterol dependent cytolysins in infection. Finally, we are interested in how certain MACPF proteins function in developmental processes and neurobiology, for example in terminal patterning in the fruit fly and in brain development in mammals. • Development of a novel small molecule treatment for cerebral malaria through inhibition of perforin (2010–2011). • (2010–2013) Wellcome Trust Seeding Drug Discovery Interim Award From a protease perspective, we are using structural and biochemical approaches to understand how proteases and protease inhibitors influence blood coagulation, fibrinolysis and tissue remodelling. Recent successes include understanding how plasma antiplasmin interacts with and inhibits the fibrinolytic enzyme plasmin. In collaboration with Dr Isabelle Lucet, Professor Andrew Wilks and Professor Bill Charman, we are studying the structure, function and biology of Plasmodium falciparum kinases, which play a fundamental role in malaria pathogenesis. NHMRC Project Grant • Structural and functional studies on perforin (2010–2013). NHMRC Program Grant • Protease systems biology (2010–2012). ARC Federation Fellowship • Membrane attack complex proteins in defence, attack and developmental biology (2010–2012). ARC Discovery Project Grant The X-ray crystal structure of perforin (Law et al., Nature, 2010) together with perforin crystals (background). Perforin eliminates virally infected and pre-cancerous cells; elevated perforin activity is associated with a range of immune driven diseases. Structural studies on perforin will allow further development of the treatment of perforin related immune diseases. • Structural and functional studies on MACPF proteins (2010–2011). ARC Super Science Fellowship • Pore forming proteins as delivery devices (2010–2012). http://research.med.monash.edu.au/whisstock/ ARC Linkage Grant • Exploring therapeutic approaches to combat celiac disease, Rossjohn/Anderson (2011–2013). ARC Super Science Fellowship • Design and fabrication of molecular machines: The nanomachines of the future, Lithgow/Rossjohn/Martin/ Strugnell (2011–2013). Anti-Cancer Council Crystal structure of Valpha10-Vbeta8.1 NKT TCR in complex with CD1d-alphaglucosylceramide (PDB ID: 3RUG). (Uldrich et al., Nature Immunology, 2011. 12: 616-623). • A structural and functional investigation into tumour rejection by NKT cells, Rossjohn/McCluskey (2010–2012). NIH RO1 • Characterisation of a novel AB5 cytotoxin, Paton/Paton/ Rossjohn (2007–2011). http://research.med.monash.edu.au/rossjohn/index.php 84 85 Facilities and Centres Facilities and Centres Facilities Australian Phenomics Network >> Australian Phenomics Network Lead Scientist: Associate Professor Moira O’Bryan Node Manager: Dr Leanne Cotton >> Macromolecular Crystallisation Facility (The Grollo Ruzzene Foundation Centre for Protein Structure) The Australian Phenomics Network (APN) provides Australian researchers with services for the creation, characterisation and cryopreservation of mouse models of human disease. >> Micromon Established in 2007, the multiple partnering institutions of the APN receive generous funding from the Australian Government's National Collaborative Research Infrastructure Strategy and Education Investment Fund, with additional funds from the National Health and Medical Research Council, state governments and research institutions, providing Australian researchers access to APN support at substantially subsidised costs. >> Monash Antibody Technologies Facility >> Monash Biomedical Proteomics Facility >> Monash Micro Imaging >> Protein Production Unit >> ARC Centre of Excellence In Structural and Functional Microbial Genomics >> Monash Comprehensive Cancer Consortium >> Monash Obesity and Diabetes Institute •• The Monash node of the Australian Phenome Bank (APB) is a repository of genetically modified mouse strains. The APB has established an archive consisting of cryopreserved mouse sperm and embryos, maintaining a centralised database detailing mouse strains stored in Australia as live or cryopreserved material. Scientists are encouraged to contribute new strains to this archive and/or search the database for mouse models of interest. Depositing researchers maintain ownership of the strain and can nominate availability to other scientists. Two Monash services are proud partners of the APN: •• The Monash Embryonic Stem (ES) Cell to Mouse service is a core APN facility which provides ready access to the global initiative to systematically inactivate every gene in the mouse genome and generate research models for all 20,000+ genes. Australian researchers choose the genetically modified ES cell line(s) of interest and lodge a request, while the service does the rest - delivering heterozygous genetically modified mice to their facility to advance their research. Microinjection of ES cells. www.australianphenomics.org.au/ Macromolecular Cystallisation Facility (The Grollo Ruzzene Foundation Centre for Protein Structure) Director: Associate Professor Matthew Wilce Manager: Dr Danuta Maksel Support: Dr Robyn Gray The Facility, which is the largest of its kind worldwide, was supported by funds from the Australian Research Council (LIEF), Monash University, Australian Regenerative Medicine Institute and the Grollo Family Foundation. Crystallography can help explain the structure and function of large molecules such as proteins, and is a valuable tool for drug design. A bottle neck to structural studies has been the production of crystals. The Crystal Palace, housed in building 16 at the Monash Clayton campus, is an automated macromolecular crystallisation facility that overcomes this bottleneck. A robot can quickly and reproducibly screen thousands of samples for the growth of crystals, work with minimal volumes, provide regular updates of these experiments via a web-based interface and integrate data through an Oracle database. The Rigaku Crystalmation robot can set up a crystallisation tray of 96 trials, aliquotting as little as 50 nL of sample per trial in approximately 7 minutes, and can store data for about 5000 96 well trays. Individual crystals are harvested and diffraction data is collected from either one of the two in-house X-ray diffractometers in building 76, or off-campus at the Australian Synchrotron Macromolecular Beamlines, in Clayton. Watching crystals grow using the Crystalmation Web-viewer. Crystalmation robotic system at Macromolecular Crystallisation Facility. www.monash.edu.au/research/infrastructure/platforms/crystallisation.html 87 Annual Report 2011 Facilities and Centres Micromon Monash Biomedical Proteomics Facility Manager: Mr Mark Cauchi Director: Professor Ian Smith Micromon specialises in providing premium quality DNA technology services to Monash researchers across all campuses, as well as external customers throughout Australia. Our premier service continues to be long-read DNA sequencing, where we provide researchers with high-quality DNA sequencing data and outstanding client support. Mass spectrometry has now become the leading tool for protein identification, quantification and sequencing. With generous funding from the Victorian State Government, NCRIS and the ARC Centre of Excellence in Structural and Functional Microbial Genetics, the Monash Biomedical Proteomics facility can offer proteomics services including: qualitative and quantitative mass spectrometry; HPLC; N-terminal sequencing; 1D and 2D SDS-PAGE. The Next-generation sequencing facility, which operates an Illumina GAIIx genetic analyzer, produces high quality genomic data that has been successfully used in various research projects, resulting in publications during the past year. This service, run by Scott Coutts, is currently being accredited with the Illumina CSPro certification for guaranteed quality delivery. Our facility is partially supported by the National Collaborative Infrastructure Scheme initiative which has been used to establish Bioplatforms Australia, incorporating Proteomics Australia. This organisation, which groups together technical facilities, enables Australian scientists to access high-end technologies at subsidised costs. The Monash Biomedical Proteomics Facility operates as the Victorian node of Proteomics Australia, with other sites in New South Wales, Queensland and South Australia. Micromon also offers services in oligonucelotide synthesis, microbial testing, and media and culture supply. The Recombinant DNA Technology workshop that is run each November was again fully booked. Aside from providing participants from around the country with training in the essential skills of molecular biology, the course provides teaching opportunities for lecturers and graduate students from the School of Biomedical Sciences. Applied Biosystems 3730 Genetic Analyzer In 2011, the facility provided proteomics services for research clients at Monash University, Victorian and Queensland institutes, and commercial companies from Victoria and Western Australia. The facility is also a member of the Victorian Platform Technologies Network. www.micromon.monash.org Our facility is operated by Dr David Steer, Ms Shane Reeve and Ms Josie Lawrence under the direction of Professor Ian Smith. Monash Antibody Technologies Facility www.med.monash.edu/biochem/facilties/proteomics Sample being loaded for protein sequencing. Director: Professor Edouard Nice Monoclonal antibodies are biological molecules that are used to detect, isolate, quantify and characterise proteins, and represent the fastest growing class of therapeutics. The monoclonal antibody market is one of the most lucrative and high growth sectors of the health biotechnology area and is estimated to be worth more than US $49 billion by 2013. Monash Micro Imaging Director: Associate Professor Ian Harper Monash Micro Imaging, the University core facility for microscopy in the life sciences, has continued to grow and expand its imaging research support in 2011. The Facility now reports to the Faculty of Medicine, Nursing and Health Sciences and the Research and Research Infrastructure Office. The School of Biomedical Sciences continues to provide a significant demand for analytical imaging, and as a result, MMI has further expanded its capacity and training. The Monash Antibody Technologies Facility (MATF) addresses an important need in the market for customised high affinity antibodies. Since January 2009 MATF has produced over 1000 antibodies for more than 175 clients. MATF customers represented all areas of the research community: 47% Monash University, 21% Australian academic, 17% Australian industry, 7.5% international academic and 7.5% international commercial. Recent operational changes to the facility have brought about improvements to key processes such as sample quality control, customer service, finance and project management. In response to our customers’ requests, MATF has provided additional services, including: antibody purification, comprehensive characterisation and development of alternative screening tools, SPR analysis and ELISA development. www.matf.monash.org The Facility continues to provide extensive imaging access across the University, with over 320 registered users, of whom 210 were trainees in new techniques or new instrumentation. In addition MMI ran 10 training workshops and short courses, and 13 PhD’s were completed using MMI instrumentation. These activities are reflected in an increasing number of publications each year, and many of the images in this annual report have been produced on MMI instruments. Research highlights include the strengthening of advanced imaging capacity, upgrading one of the optical workstations to confocal capacity (Nikon C1), converting a Leica SP5 inverted multiphoton microscope to an upright configuration to facilitate small animal imaging for Developmental Biology and Regenerative Medicine researchers, and the establishment of a cryo-preparations laboratory for the MMI BioEM Facility. Robotic workstations at MATF. In addition, in August a Zeiss 780 confocal/multiphoton microscope with FCS (funded by Australian Regenerative Medicine Institute) was installed in the Advanced Optical Imaging Facility (Clayton) for studies of mouse embryo development, with resolution capabilities from cellular structure to single molecule detection. ARMI and MMI staff celebrating the installation of the new Zeiss LSM780 confocal/ multiphoton microscope in August 2011. Present, from left to right: Juan Silva (ARMI), Stephen Firth (MMI), Professor Nadia Rosenthal (Director, ARMI), Associate Professor Ian Harper (Director, MMI), Gurpreet Kaur and Dr Nico Plachta (Group Leader, ARMI). www.microimaging.monash.org 88 89 Annual Report 2011 Protein Production Unit Scientific Director: Professor Stephen Bottomley The Protein Production Unit provides a dedicated service to academic and industry clients who wish to outsource protein production and quality assurance. In 2011, over 1850 individual proteins were produced and purified in this facility from a variety of recombinant sources. These proteins, which were isolated with the aid of liquid handling robots, were used for antibody and vaccine production, structural biology studies and biomedical/biophysical research. Facilities and Centres In our custom-built facility we provide the following services: protein purification, refolding of insoluble proteins, expression scouting and purification protocol development. We can also customise high throughput methods for our clients and recommend approaches to stabilise or refold proteins. In 2011, we purchased an AKTA avant 25 FPLC scouting unit to assist with the development of purification protocols. In 2012, we will be able to offer a full range of expression vehicles for the expression and purification of recombinant proteins from E.coli, yeast, insect and mammalian cells. This facility is operated by Dr Noelene Quinsey and Mr Nik Sotirellis under the direction of Professor Stephen Bottomley. Centres ARC Centre of Excellence in Structural and Functional Microbial Genomics Director: Professor Ben Adler The ARC Centre of Excellence in Structural and Functional Microbial Genomics brings together a team of internationallyrenowned researchers with complementary expertise from the School of Biomedical Sciences at Monash University. As part of National Science Week, the ARC Centre in Structural and Functional Microbial Genomics organised a public lecture at BMW Edge, at Federation Square. Dr Paul Johnson from Austin Health presented the lecture The End of Antibiotics, which was followed by a panel discussion and questions from the public. We research microbial pathogens and the hosts they infect, focussing on diseases of importance to the Australian primary industry. We aim to develop new veterinary vaccines, diagnostics tests, and identify novel antimicrobial drug targets. We use a genomics-based approach to identify virulent genes of pathogens, and then seek to understand the structure and function of the proteins they produce and how these organisms cause disease. We work collaboratively with scientists in Australia and internationally and we also partner with Pfizer Animal Health and Intervet Schering-Plough. Recently we: •• Registered a fowl cholera vaccine to be used in the market; From left to right: Dr Noelene Quinsey, Mr Nik Sotirellis and Professor Stephen Bottomley. http://proteinproductionunit.med.monash.edu.au Protein Production Unit laboratory space. •• Identified a new sub-population of T-cells in the immune system; •• Demonstrated that a larval-specific antigen against the parasitic worm, Haemonchus contortus protects vaccinated sheep in the field; •• Solved the structure and genetic basis of cell surface lipopolysaccharide assembly in all 16 known serotypes of Pasteurella multocida, the cause of fowl cholera; Development of therapeutics, diagnostics and vaccines against microbial pathogens using the Centre’s research infrastructure and expertise. •• Discovered how mammalian cells overcome infection with Burkholderia pseudomallei, the cause of melioidosis; •• Solved the structures of two important malarial virulence factors in complex with novel compounds; and •• Identified a candidate vaccine for sheep footrot. www.microbialgenomics.net 90 91 Annual Report 2011 Monash Comprehensive Cancer Consortium Interim Research Director: Professor Neil Watkins Advisory Council Chair: Professor David de Kretser AC Management Committee Chair: Professor Gail Risbridger Chief Operating Officer: Ms Anna Kilgour The Monash Comprehensive Consortium (MCCC) is one of three major cancer research nodes in Victoria’s system of integrated cancer research and care, and services approximately 30 per cent of Victoria’s cancer patients. MCCC partner organisations include Monash University, Monash Institute of Medical Research, Prince Henry's Institute, Southern Health, Alfred Health, Cabrini Health, Peninsula Health and Southern Melbourne Integrated Cancer Services. The consortium’s role is to bring together the research and clinical strengths of its partners to deliver the best possible outcomes for cancer patients. www.mccc.edu.au Monash Obesity and Diabetes Institute Director: Professor Michael Cowley The Monash Obesity and Diabetes Institute (MODI™) comprises of obesity, diabetes and metabolic disease researchers who aim to translate research results into clinical treatments for these and related disorders. The Institute is embedded within the School of Biomedical Sciences, which facilitates collaborations with scientists in several departments. MODI™ also hopes to raise the profile of obesity and diabetes awareness in the community and the need to tackle these problems as what we are doing now is not working. Key focus of research groups: Professor Michael Cowley is the Director of MODI™ and is interested in the hormone leptin, which our fat cells secrete to control appetite, metabolism and body weight. He is investigating if high leptin levels in obese mammals contribute to pathologically high blood pressure, increased heart rate and diabetes. If so, it may be possible to develop treatments that improve a patient's metabolic condition by blocking leptin action. www.modi.monash.edu.au/ 92 Professor Tony Tiganis studies the regulation of insulin signalling in the brain and how inflammation contributes to the development of diabetes and obesity. Associate Professor Matthew Watt uses genetic and pharmacological approaches to investigate the link between obesity and the development of Type 2 diabetes. Professor Brian Oldfield studies the role that the brain plays in controlling food intake and the burning of energy, which ultimately leads to changes in body weight and possibly obesity. Professor Iain Clarke investigates how hormones in the brain control metabolic function, food intake, and their role in obesity. Grants and Funding >> National and international research support >> Patents Grants and Funding 2006 2007 2008 2009 2010 2011 NHMRC Projects $7,101,926 $9,984,961 $10,581,847 $11,060,072 $13,676,111 $16,196,688 NHMRC Programs $5,259,252 $5,970,800 $7,464,703 $7,030,448 $7,189,305 $6,009,845 $437,470 $786,720 $1,225,460 $606,123 $1,421,647 $4,990,393 $5,524,382 $5,718,726 $6,472,863 $6,786,280 $6,593,196 $17,351,572 $21,917,614 $24,551,996 $25,788,843 $28,257,819 $30,221,376 ARC Projects (Discovery and Linkage) $2,761,966 $2,314,257 $2,934,206 $4,637,308 $5,184,242 $5,304,060 ARC Centres $1,826,565 $2,314,952 $2,468,678 $3,048,225 $2,814,765 $1,602,734 ARC Fellowships and Scholarships (people support) $158,111 $322,625 $663,380 $1,105,422 $1,264,116 $2,094,133 ARC Other (Infrastructure and Equipment Grants) $724,660 $1,700,000 $400,000 $1,400,000 $485,695 $829,140 $5,471,302 $6,651,834 $6,466,264 $10,190,955 $9,748,818 $9,830,067 NIH, NHF, CRC, AKF and donations $16,416,182 $20,434,059 $14,149,547 $9,036,248 $10,623,115 $8,726,203 Total Income $39,239,056 $49,003,507 $45,167,807 $45,016,046 $48,629,752 $48,777,646 NHMRC Grants Income NHMRC Other (Development and Equipment Grants) NHMRC Fellowships and Scholarships (people support) NHMRC Total ARC Grants Income ARC Total Other National and International Income Annual Report 2011 Grants and Funding Research Income 2006 to 2011 Major Grants Commencing in 2012 Source Chief Investigator and Project Title ARC Discovery Grants Funding ($ million) 24.5 22.0 17.3 20.4 16.4 6.6 Period Total Funds Beddoe T: Host-pathogen interactions: The role of mimicry. 3 2012-2014 $180,000 Bird P: The role of the protease inhibitor Serpinb9 in antigen cross-presentation by dendritic cells. 3 2012-2014 $315,000 Clarke I: Muscling in on the brain. 3 2012-2014 $270,000 Clarke I: Endogenous and environmental regulation of energy expenditure in skeletal muscle. 3 2012-2014 $540,000 Coulibaly F: Spindles of insect viruses: Structure, function and engineering of natural protein crystals 3 2012-2014 $315,000 Dunstone M: The mechanism of pore formation by membrane attack complex/perforin-like proteins. 3 2012-2014 $280,000 Mackay C: Mechanisms connecting diet, metabolism, gut microbiota and immunity. 3 2012-2014 $345,000 Meeusen E: Designing new generation adjuvants for allergy and parasite vaccines. 3 2012-2014 $315,000 O'Bryan M: HEN1 is a regulator of piRNA metabolism, transcriptional regulation and mammalian male 3 2012-2014 $344,000 3 2012-2014 $270,000 Bakola S: Understanding the function of a visual pathway to the limbic cortex. 3 2012-2014 $375,000 Furic L: Estrogen-mediated regulation of gene expression via transcriptional and translational control: 3 2012-2014 $375,000 Jeffrey K: Argonaute proteins and the mammalian antiviral response. 3 2012-2014 $375,000 Borg N: The regulation of anti-viral immunity by host and viral proteins. 4 2011-2015 $634,528 Spencer S: Developmental programming of adult stress responses: Early life nutrition permanently 4 2011-2015 $ 707,797 as microparticles for vaccine delivery. 14.1 5.5 Duration (Years) 6.5 fertility. Smith J: The critical role of kisspeptin/neurokinin/dynorphin (KNDy) neurons in gonadotropin releasing 2006 2007 hormone (GnRH) release. 2008 ARC Early Career Fellowships 30.2 28.3 25.8 Complementary, synergistic or opposing responses? ARC Future Funding ($ million) Fellowships alters stress and immune function. 10.2 9.0 9.7 10.6 9.8 8.7 ARC LIEF Grant Whisstock J: A centre for structural cryo-electron microscopy. 1 2012 $640,000 ARC Linkage Grant Meeusen E: Exploiting the lymphatic system for next generation vaccine development. 3 2012-2014 $570,000 NHMRC Career Polo J: Determining the events that occur during the reprogramming of different adult cells into 4 2012-2015 $391,076 Development Award embryonic stem-like cells and the capacity of becoming another specific adult cell during this process. Aljofan M: New targets for antiviral therapies. 4 2012-2015 $294,892 Berry R: The mechanism responsible for quality control in the immune system. 4 2012-2015 $294,892 Lawrence M: Stem cells in the prostate cancer microenvironment. 4 2012-2015 $294,892 Robertson A: Understanding the relationship between cellular sterols and amyloid toxicity that occurs 4 2012-2015 $320,628 Rossjohn J: Australia Fellowship. 5 2012-2016 $4,000,000 Buckle A: Research Fellowship SRF B. 5 2012-2016 $641,855 Fellowship NHMRC Early Career Fellowships 2009 2010 2011 in many neurodegenerative diseases. NHMRC Total ARC Total Other National and International Income Research Income 2011 NHMRC Fellowships Oldfield B: Reserch Fellowship PRF. 5 2012-2016 $702,795 NHMRC Project Andrews Z: Carnitine palmitoyl transferase 1 in POMC neurons controls glucose homeostasis and 3 2012-2014 $458,510 Grants body weight. Andrews Z: Hormonal regulation of NPY neurons in the arcuate nucleus of the hypothalamus. 3 2012-2014 $564,680 Anthony R: SIGN receptors and the antiinflammatory activity of sialylated IgG Fcs. 3 2012-2014 $536,325 Bertram J: Understanding the causes of childhood congenital anomalies of the kidney and 3 2012-2014 $589,700 Clarke I: Gonadotropin inhibitory hormone (GnIH); a negative regulator of reproduction. 3 2012-2014 $727,425 Cowley M: Can blockade of leptin action in the brain reduce blood pressure in obese mice? 3 2012-2014 $631,010 Denton K: Consequences of elevated maternal glucocorticoids for early childhood renal 3 2012-2014 $584,685 Evans R: The role of tissue hypoxia in the evolution of kidney disease. 3 2012-2014 $492,308 Jans D: The essential nuclear transporter Importin 13: Key role in brain and testis. 3 2012-2014 $592,350 Jans D: Enhanced nuclear transport in transformed cells: Implications for cancer treatment. 3 2012-2014 $607,350 Jeffrey K: Argonaute proteins in the mammalian antiviral response. 3 2012-2014 $505,586 Kaiserman D: Investigating the role of SERPINB6 in cochlear function and deafness. 3 2012-2014 $550,850 Law R: Structural studies on plasminogen. 3 2012-2014 $346,175 Loveland K: Hedgehog signalling in spermatogenesis. 3 2012-2014 $506,175 urinary tract. Other National and International Income: 18% development and function. ARC Total: 20% 96 NHMRC Total: 62% 97 Annual Report 2011 Grants and Funding Major Grants Commencing in 2012 Source Chief Investigator and Project Title NHMRC Project School of Biomedical Sciences Patents 2011 Duration (Years) Period Total Funds Lyras D: Novel therapeutic and preventive strategies for Clostridium difficile infections. 3 2012-2014 $491,325 Lyras D: Expression and secretion of large clostridial toxins from the pathogenic clostridia. 3 2012-2014 $321,175 McMenamin P: Mechanisms of Novel TLR9 mediated intraocular inflammation. 3 2012-2014 Mitchell C: Phosphoinositide 3-kinase signalling and skeletal muscle mass. 3 Naderer T: Diabolic regulation of macrophage cell death pathways by Legionella. Title Filing Date R Rajan , L Marsden Provisional Monash owned Constrained immunogenic compositions and uses. 23/06/11 F Coulibaly, A Mansell, R Ffrench PCT Jointly owned Detection of EPHA3 as a marker of the presence of a solid tumor. 20/06/11 M Lackmann, C To National phase US Licensed $427,260 X-ray crystal structure of human plasminogen. 08/06/11 J Whisstock, R Law, P Coughlan Provisional Monash owned 2012-2014 $577,350 A method for enriching cardiomyocytes. 01/06/11 D Elliott, A Elefanty, E Stanley Provisional Jointly owned 3 2012-2014 $596,010 Crystal structure of perforin and methods for its use. Method of 17/05/11 J Whisstock, R Law, J Trapani, PCT Jointly owned O'Bryan M: Katanin p80 is a key regulator of microtubule dynamics and male fertility. 3 2012-2014 $582,350 crystallising perforin. Rajan R: Sensory cortex processing changes underlying brain and behaviour deficits caused by 3 2012-2014 $557,760 Diagnostic and prognostic assay for breast cancer. PCT Monash owned PCT Monash owned Rajan R: Understanding the role of caudal auditory belt areas in perception of complex sounds. I Voskoboinik 03/02/11 3 2012-2014 $747,221 Risbridger G: Estrogen therapy for castrate resistant prostate cancer. 3 2012-2014 $513,675 Rosa M: Understanding the organisation of the medial parietal cortex: Sensorimotor integration for 3 2012-2014 $533,510 3 2012-2014 $571,010 Smyth I: Involvement of the Asciz gene in kidney development and disease. Taylor R: Stromal hedgehog signalling in prostate cancer. 3 2012-2014 $311,175 Traven A: An investigation into pathogen specific factors required for drug resistance and viability of 3 2012-2014 $326,175 Widdop R: Insulin regulated aminopeptidase: A new cardiovascular target. 3 2012-2014 $649,685 Coulibaly F: Immunogenicity study of HIV Env MicroCubes. 1 2011-2012 $109,000 Methods for regulating blood glucose levels. 25/01/11 HIV and Hepatitis A method for treating obesity. 16/07/10 T Tiganis, M Cowley PCT Monash owned Cell culture media. 08/04/10 A Elefanty US only Monash owned A method of treating diabetes by inhibition of TCPTP in the liver. 02/02/10 T Tiganis, M Tremblay, Provisional Monash owned S McGowan, C Porter, National Phase AU, Jointly owned J Whisstock, J Lowther, EP and US S Andrikopoulos Crystal structures of malarial aminopeptidase or M1 malaria protein. 12/02/09 Jans D: Nuclear transport Inhibitors as HIV anti-virals. 1 2011-2012 $113,000 Netter H: Immunogenicity of virus-like particles contaning HIV-1 neutralising epitopes and 1 2011-2012 $112,000 1 2012 $74,175 determination of the quality of the immune response. Ramaciotti Vinh A: Defining hypertension down to the T cell. 1 2012 $68,000 McMenamin P: The role of resident corneal immune cells in the development of diabetes associated 1 2012 $59,991 1 2012 $52,340 body insulin resistance? Broughton B: How does G Protein-Coupled Receptor 30 (GPR30) affect stroke outcome? 2 2012-2013 $210,000 Blood Pressure EphA3 antibodies for the treatment of solid tumours. Sobey C: Using human amnion stem cells to treat stroke. 2 2012-2013 $130,000 J Whisstock, S McGowan, National Phase, A Buckle US only J Rood, A Keyburn National Phase, Jointly owned Assigned M Lackmann, C To National Phase CN Licensed AU, EP, NZ and US Identification of candidate vaccine antigens from Dichelobacter nodosus 19/12/07 (footrot vaccine). Regulation of metalloprotease cleavage of cell surface proteins. 13/09/07 19/12/05 J Rood, K al-Hasani, J Boyce, National Phase AU, D Parker EP, NZ and US J Whisstock, R Law, A Buckle, National Phase G Fenalti, M Rowley US and EP M Lackmann, PW Janes, DB National Phase. Nikolov, N Saha Granted US Monash owned Monash owned Jointly owned and NZ. Methods for producing blood products from pluripotent cells in 19/11/04 E Stanley cell culture. Eph/ephrin mediated modulation of cell adhesion and tumour A method of modulating cellular activity and molecules for use therein. Clostridium expression system. 98 10/03/08 Granted AU. Monash owned Pending in US. 09/02/04 cell metastasis. Research Heart Foundation 06/06/08 corneal neuropathy. Watt M: Does lipid accumulation in hypothalamic neurons contribute to the development of whole- Foundation for High 02/07/08 US only Crystal structures of both isoforms of GAD. Foundation Research Trust C Stack, S Donnelly, J Dalton Octameric protein in bionanotechnology. Clostridial toxin netB. Virology Research M Cowley, P Enriori, R Brown, I Clarke, B Henry, M Rudaz Candida albicans. Bertram J: Optical Projection Tomography (OPT) machine. T Tiganis, B Shields, C McLean, R Sutherland goal directed behaviour. Diabetes Australia Status 18/11/11 traumatic brain injury. Clive and Vera Patent Surgical implant tool. Grants Australian Centre for Monash Inventor/s 04/09/03 06/04/98 M Lackmann, S Wimmer- National Phase US Kleikamp, A Scott, C Vearing, and EP. Granted A Boyd in AU. M Aguilar, P Perlmutter, J National Phase AU Rossjohn, A Purcell and US J Rood, D Lyras Granted in US Jointly owned Jointly owned Licensed 99 Education >> Teaching news >> Staff and student programs >> Centre for human anatomy education >> Awards and prizes First year Bachelor of biomedical science and double-degree students at Transition Day. Annual Report 2011 Education Education in the School of Biomedical Sciences (SOBS) Professor Phillip Nagley: Chair of School Education Committee, Director of Biomedical Education Advancement Unit Associate Professor Yvonne Hodgson: Manager of Academic Programs and Quality, School of Biomedical Sciences Associate Professor Marilyn Baird: Head, Department of Medical Imaging and Radiation Sciences and Convenor, Bachelor of Radiography and Medical Imaging Professor Paul McMenamin: Director, Centre for Human Anatomy Education School education committee Our committee held 10 meetings during 2011. We achieved the following: • Developed policy to maintain international best practice in teaching, learning and assessment; • Plannied upgrade of learning spaces in the School educational precinct; • Supported the transition of academic staff to newly introduced education-focussed roles; • Explored ways to enhance the already substantial links between undergraduate education and biomedical research; and Biomedical education advancement unit This unit focuses on educational leadership and staff development and is led by Professor Phillip Nagley, with Dr Sharon Flecknoe and Jane Sun. Jane left in August to accept a position in another faculty. BEAU works closely with the SOBS Education Committee, networks with educators in Biomedical Science and undertakes specific projects on behalf of the School. BEAU: • Helped Bioscience staff at Monash Peninsula campus achieve their educational goals in Allied Health, including incorporating Bioscience teaching into the new Nursing program at Berwick campus; Overview of undergraduate teaching The School teaches students enrolled in diverse undergraduate and professional postgraduate courses. In 2011, the net undergraduate and postgraduate coursework teaching generated approximately $12.2 million income for the School and its associated partners. The School manages undergraduate programs in two disciplines: Biomedical Science, and Radiography and Medical Imaging. The 2011 income generated by the Biomedical Science course and its associated programs (Scholar, Advanced Honours, BMS Honours and the doubled degree programs) was approximately $4.1 million, with an additional $1.4 million from the Radiography and Medical Imaging undergraduate course. About 35% of the total income is passed on to faculty and non-faculty School partners. • Provided staff development opportunities, enhancing educational skills and experience; Teaching income from non-School managed courses generated a further $8.2 million for the School. The largest income ($5.3 million) was provided by departmental teaching of BSc units, including the BSc Honours units. Teaching of MBBS and allied health students at the Peninsula campus generated a further $2.1 million and $0.8 million for the School, respectively. • Combined work experience placements for high school students with a leadership program for postgraduate students at SOBS; In 2011, the School supervised 109 students undertaking honours programs (BSc 60, BMS 49). The breakdown of teaching load and School income is shown in the table below. • Maintained close links with John Monash Science School and delivered both Biomedical Science and bioinformatics electives at this new secondary school; and • Ran the BioEYES program involving zebrafish developmental biology in several primary and secondary schools. • Developed and implemented improved units for nursing students at Monash Peninsula and Gippsland campuses. Net School/ Department Income in 2011 School Managed Courses Enrolments Total Biomedical Science Courses 766 $2,597,784 Radiography and Medical Imaging Courses 222 $897,796 Teaching in Non-School Managed Courses EFTSL# Science Units 654 $5,276,505 MBBS Teaching 385 $2,075,505 Peninsula Teaching 103 $834,752 Total Undergraduate Teaching Income Postgraduate School Courses Medical Imaging and Radiation Sciences Net Coursework Teaching Income $11,682,313 Enrolments 91 $564,933 $12,247,246 #EFTSL: Equivalent Full Time Student Load Work experience student Simon Zhing (left) with postgraduate mentor Katrina Mirabito (right). 102 John Monash Science School students engrossed in BioEYES work. 103 Annual Report 2011 Education Biomedical science programs Undergraduate research programs August 2011 saw the inaugural meeting of the Biomedical Science Advisory Board. The Board consists of current and former students, industry members and staff from representative graduate courses. The feedback from the Advisory Board was positive and the minutes of the meeting were presented to the Faculty. Undergraduate students were welcomed into School laboratories through the Research in Action units offered by the departments of Anatomy and Developmental Biology, Biochemistry and Molecular Biology, Microbiology, Monash Immunology and Stem Cell Laboratories, Pharmacology and Physiology. 71 third year undergraduate students completed small research projects over one semester in diverse biomedical areas. These units are popular, with a 51% increase in students choosing these units in the past four years. Also in 2011, Monash Biomedical Science students participated in a benchmarking survey with the University of Queensland. Final year students were asked about skill acquisition during their studies. Results from the Monash survey were presented at the Assessment Institute in Indianapolis by the Course Convenor, Associate Professor Yvonne Hodgson. Now in its second year, the Talented Student Program continues to grow, with 33 students enrolled. This program identifies and nurtures high-achieving students who are interested in pursuing a career in medical research. They are exposed to research programs and researchers through extracurricular activities: mentoring, research platform tours and seminars. This year, students toured the Australian Synchrotron and the Monash flow cytometry facility - FlowCore. The program is open to students enrolled in the Bachelor of Biomedical Science Scholars or the Bachelor of Biomedical Science Advanced Honours Program. The Bachelor of Biomedical Science Honours program, convened by Associate Professor Tim Cole, attracted 53 students into the School to undertake a research project. The students excelled, with 69% achieving a grade of First Class Honours. Radiography and medical radiations programs In 2010, the Master of Medical Radiations program replaced the Nuclear Medicine stream with a new stream in Medical Ultrasound. With funding support from I-MED MIA Victoria, we have been able to develop new course materials and provide supervised clinical placements, which is critical for student learning. Philips Healthcare has also generously provided three ultrasound machines for a new ultrasound teaching laboratory, which will help students develop their pre-clinical skills. The Medical Ultrasound stream has been accredited by the Australasian Sonographers Accreditation Registry for the maximum period of five years. Currently, the Radiation Therapy stream is undergoing its re-accreditation process with the Australian Institute of Radiography. Enrolment numbers in the Bachelor of Radiography and Medical Imaging course have been steadily increasing, with over 60 students in years one and two. As a result, the curriculum has been modified in year four. From 2012, students electing to study RAD4080 Selected Topics in Medical Imaging will be able to choose one of the following streams: advanced CT; advanced medical ultrasound; paediatric imaging and professional education and leadership. Graduates from the Bachelor of Radiography and Medical Imaging continue to enjoy full employment upon graduation. Also, it was pleasing to learn that in the recent National Course Experience Questionnaire overall satisfaction with the course was 95%, with just under a 50% response rate. Throughout 2011, considerable planning has taken place regarding the new radiography teaching laboratory which will incorporate clinical quality imaging systems. International programs The articulation program with the Republic Polytechnic in Singapore continued in 2011. This program has been in place since 2006 and has seen a total of 82 students come to Monash to undertake the third year of the Biomedical Science degree course. About one-third of these students stay at Monash to complete honours, PhD and other postgraduate courses. To date, 19 students have enrolled in Biomedical Science Honours, 2 students have undertaken a Graduate Diploma in Reproductive Sciences, 5 students have completed a Master of Biomedical Science part one, 2 have completed a Master of Biomedical Science and 2 students have undertaken a PhD. In addition to the Republic Polytechnic program, the School also teaches international students who undertake degree programs in Biomedical Science and Science. For the Biomedical Science course, approximately 4% of students are international: 3% are from New Zealand and 5% are permanent residents. Our school also teaches several units at the Malaysia Sunway campus. These units are taught by staff in the departments of Microbiology (MIC2011) and Physiology (PHY2021 and PHY2032) and contribute to the Bachelor of Medical Bioscience course. Teaching across campuses requires effective communication and collaboration between Clayton-based staff and those at the Malaysian campus. Student support The School organised the annual one-day transition program for first year students in February. Approximately 200 students attended this transition program, which focused on helping students form new friendships, meet staff and senior students, and become familiar with the campus. The program featured a treasure hunt, trust games and a mini film festival. Sharon Flecknoe and Jane Sun, from BEAU, worked closely with program director Associate Professor Yvonne Hodgson to organise and run the program. Also, higher year biomedical science students led each group of first year students, while postgraduate students in the School acted as tutors for each of the scheduled activities. This is an important program as feedback from participants indicate that this program helps students transition successfully into university life. In 2011, the School continued to support the student-run Biomedical Science Society, which organises events, including: an annual camp for biomedical science students, industry mixer nights, University Open Day activities and Transition Program. The society plays an important role in the social and academic lives of biomedical science students. The 2011 Biomedical Science honours class. 104 Simulated learning at Monash Medical Centre. Biomedical sciences students modelling DNA. 105 Education PASS program Centre for human anatomy education The Peer-Assisted Study Session (PASS) program continued in 2011 for first year students enrolled in BMS1021 and BMS1062. This initiative, which is organised by Adrian Devey from the Vice Chancellor (Education) office, allows high achieving senior students to act as student mentors and give weekly tutorials sessions to first-year students. The students, who participated in the program, interacted with older peers and enjoyed the informal tutorial sessions. The Centre delivers anatomy teaching to students studying medicine at three Monash campuses: Clayton, Gippsland and Malaysia, Kuala Lumpar. In 2011 one of the Biomedical Science PASS Leaders, Claudia Ashkar, won the Australasian PASS Leader Award, the first time that Monash was successful on the international stage. Claudia received her award at the National PASS Forum in Sydney in September. Student awards and prizes The 2011 Faculty Prizes and Award Ceremony for Academic Excellence was held in April. The top two students from each year in the Bachelor of Biomedical Science course received $200 and the top student from the honours program received $500. Industry and professional bodies support the radiography course and provide at least two $200 prizes in each year level of the course. Biomedical science teaching newsletter The Centre for Human Anatomy Education was recently reviewed and the activities in both teaching and research were highly commended. A number of recommendations were made that will allow the Director Professor Paul McMenamin to continue to push for changes in learning and teaching activities in the Centre. The goal is to make it an exemplar internationally when it comes to the practice of anatomy teaching and as a leader in innovation and research in this field. Recently, the Learning Resource area has had some cosmetic changes. There have been alterations to the entrance and teaching spaces to make them more appealing and interesting for students. In other news, Dr Colin McHenry, who has research interests in comparative vertebrate morphology and computational biomechanics, recently joined the Centre and will strengthen our anatomical sciences research. He studies diverse species, from sharks to lizards and humans. Staff professional development and support Two issues of the School newsletter were written by Thomas Dillane and edited by Associate Professor Yvonne Hodgson. The publications, which were distributed to staff and students, profiled young researchers and described trends in teaching and related topics. In 2009, the newsletter was incorporated into the School’s publication Biomed Benchmark. Demonstrator/tutor training Teaching facilities and equipment Bioscience education scholarship team Refurbishment and upgrades of facilities The ground floor of Building 13D is currently being renovated to accommodate an X-ray laboratory and teaching laboratories for Radiography and Medical Imaging students. Work is expected to be completed by the end of January 2012. Plans for upgrading other areas of the SOBS teaching precinct are in progress. New practical class equipment In 2011, the Department of Physiology replaced the power lab set-ups in all teaching laboratories. A total of 30 life science power lab and lab tutor set-ups were purchased from AD Instruments at an approximate cost of $10,000 each. The new equipment is being used for second and third year practical classes for students studying BSc, BMS, Nutrition and Radiography courses, and also for new practical classes for MBBS students. Claudia Ashkar with her Australasian PASS Leader Award. The training program for sessional staff (demonstrators) was run in semesters one and two for 47 and 20 staff, respectively. All incoming student demonstrators and tutors, who teach units delivered by SOBS departments, receive training in practical and small group teaching. Collaborative university biomedical education network In 2011, Associate Professor Yvonne Hodgson and Dr Janet Macaulay successfully obtained an ALTC Discipline Learning and Teaching Network grant as team members of the Collaborative University Biomedical Education Network (CUBENET). This national network will foster dialogue, communication and collaboration with tertiary biomedical educators, both nationally and internationally, and create a sustainable, innovative biomedical curriculum that addresses the challenges that face the sector. At the heart of CUBENET will be a website and newsletter featuring updates from working parties, reports, lectures by visiting academics, and information about strategic funding opportunities and participating partners. CUBENET will also organise workshops, retreats and forums, the first of which will be the National Biomedical Education Forum in Canberra, in December 2011. Education awards On 2 March, Dr Richard Loiacono from the Department of Pharmacology received the Dean’s Awards for Excellence in Education (Quality) from Professor Steve Wesselingh. Dr Loiacono was acknowledged for the outstanding quality of his teaching activities and unit coordination. His long-standing commitment to student-focussed learning is reflected by MonQueST teaching surveys ranking him one of the top lecturers at Monash University. Dr Loiacono teaches pharmacology in Biomedical Science, Medicine, Science, Radiography and Neuroscience courses. The Bioscience Education Scholarship Team (BEST) was formed in 2010 to provide a forum for educators with an interest in education research to discuss pertinent issues in higher education and to establish collaborative projects. In 2011 BEST held 10 meetings. At the end of 2011 BEST established an international arm, extending membership to staff at Purdue University in the US. Also in 2011, the Office of the Pro-Vice Chancellor (Learning and Teaching) formed a network of staff participating in excellence in education research, called MEERG. All members of BEST have since joined this university-wide group. Measuring energy expenditure by indirect colorimetry. An example of body painting performed by a group of life drawing artists. 107 Postgraduate Research >> MBio graduate school >> Higher degree research enrolments and completions >> Scholarships Postgraduate Research 2009 2010 2011 Department of Anatomy and Developmental Biology 28 31 31 Department of Biochemistry and Molecular Biology 109 110 111 6 11 11 Department of Microbiology 47 51 56 Monash Immunology and Stem Cell Laboratories 32 30 28 Department of Pharmacology 28 22 25 Department of Physiology 37 30 30 287 285 292 Anatomy and Developmental Biology 11 5 7 Biochemistry and Molecular Biology 18 28 18 1 1 1 10 9 7 MISCL 8 5 3 Pharmacology 7 5 7 Physiology 10 6 11 Total 65 59 54 PhD and Masters by Research enrolments* in SOBS Departments Department of Medical Imaging and Radiation Sciences Total PhD and Masters by Research completions* in SOBS Departments Medical Imaging and Radiation Sciences Microbiology *Head count as at 31 December each year Annual Report 2011 Postgraduate Research Associate Professor Sharon Ricardo: Director, MBio Graduate School Dr Shae-Lee Cox: Senior Project Manager, MBio Graduate School MBio graduate school In 2011 the MBio Graduate School provided enhanced scientific and professional development training for the 292 Higher Degree Research (HDR) students enrolled in the School of Biomedical Sciences and Australian Regenerative Medicine Institute, at the Monash Clayton campus. HDR enrolments have remained consistent over the past three years as shown in the table on page 109. We also include HDR student completion data. Highlights Scholarships In 2011, the MBio Graduate School continued to perform strongly in the end-of-year postgraduate scholarships round, successfully obtaining 36 out of 101 university-wide stipend scholarships awarded to the Faculty. We also received one of the Faculty postgraduate excellence awards that are offered to the top eight applicants on the Faculty’s order of merit list. International students did exceptionally well, with six students receiving tuition fee scholarships out of the 12 awarded to the Faculty. Students came from Sri Lanka, Malaysia, South Africa, Iran, Vietnam, Brunei Darussalam, Peru and Mauritius to study in the School. Our students also received three NHMRC postgraduate scholarships to undertake postgraduate studies in the Departments of Biochemistry and Molecular Biology, and Physiology. Under the direction of Associate Professor Sharon Ricardo, we have initiated the following: Scholarship •• Published a regular e-bulletin for HDR students, promoting HDR activities and events; Australian Postgraduate Award 17 •• Developed candidature confirmation process guidelines to ensure consistent training, milestone reporting and support for students across departments; Monash Graduate Scholarship 6 Faculty Postgraduate Research Scholarship 6 Endeavour International Postgraduate Research Scholarship 1 Monash International Postgraduate Research Scholarship 4 Faculty of Medicine International Postgraduate Scholarship 2 NHMRC Postgraduate Scholarships 3 •• Hosted mental health awareness seminars for staff and students; •• Provided dedicated writing spaces for students to complete their theses; and •• Initiated a PhD leadership program, together with BEAU, for HDR students to mentor high school students from John Monash Science School. Student awards and prizes This year, the MBio Graduate School hosted the inaugural Anthony Koelmeyer International PhD Excellence Awards. Three lucky PhD students received $1,500 each towards international conference costs and research training in overseas laboratories in order to enhance their PhD experience. Total Number awarded 39 The MBio Graduate School is grateful for the funding support from the Office of the Deputy-Vice Chancellor (Research), Faculty of Medicine, Nursing and Health Sciences and School of Biomedical Sciences. For more information about us, please refer to our website at www.med.monash.edu.au/mbio-gradschool/. The successful students were: •• Andrew Clarke, Department of Biochemistry and Molecular Biology; •• Sarah Hass Lockie, Department of Physiology; and •• Jeffrey Moore, Department of Pharmacology. We also hosted the annual Three Minute Thesis competition for HDR students. Mohsin Sarwar, from the Department of Pharmacology, was the winner and received a $600 travel grant. Second and third places were awarded to Priyangi Alwis (Department of Microbiology) and Sarah Wilkinson (Department of Anatomy and Developmental Biology), respectively. First and second prize winners went on to represent SOBS in the faculty final. Anthony Koelmeyer Award recipients. From left to right: Jeffrey Moore, Sarah Haas Lockie and Andrew Clarke. 110 Ghizal Siddiqui, a PhD student from the Department of Microbiology. Administration >> News Annual Report 2011 School Administration Mr Doug McGregor: School Manager Vicki Burkitt continues her contribution to the School in the new role of Communications and Projects Officer. 2011 was again a significant year for School administrative staff. Also, in the second half of 2011 the Biomedical sciences student services team re-located to building 77 so that the School now has a single reception area for both staff and students. This team consisting of: On 31 January, the University’s financial services enhancement and HR business partnership models were implemented. Under these models, most finance and all HR services were consolidated under central University management in a hub-type structure. In the case of SOBS, many staff previously in finance and HR roles within the School transferred to the new structure and continued to provide relevant services to the School, albeit under new management. Other staff obtained new roles in other hubs or took advantage of the voluntary severance package offered in late 2010. At the same time, the School animal ethics team was incorporated into the Faculty animal ethics office and re-located to building 13C under the management of the Faculty Office. The School’s Animal Ethics Officer Jane McCausland left the School as part of this restructure but subsequently returned to take up a new role as Administration Officer in the School Office. As a result of these changes, the School Office now comprises a small group of staff, who provide general administration, infrastructure services, marketing and communications, and operational budget services to the School. This team is managed by the School Manager Doug McGregor, while School Finance Manager Alan Hunter oversees the School operational budgets. Alan is supported by Kim Gan, a Senior Management Accountant. Dr Isabel Roberts continues in her role as Manager, Infrastructure. She is supported by Building Managers Ian McPherson and Jeff Wright, Assistant Building Manager Eddie Kadir and Technical Officer John Peavey. During 2011, Isabel’s team provided infrastructure support to the School as well as CSIRO labs in building 75. They also continued to develop the School media preparation and central wash facility in building 77. Supporting Isabel in these areas are Shubha Lakkola and Radana Ninkovic. School of Biomedical Sciences infrastructure team. From left to right: Ms Radana Ninkovic, Mr Ian McPherson, Dr Isabel Roberts, Mr John Peavey, Ms Shubha Lakkola, Mr Jeffrey Wright, Ms Renae Hayle and Mr Eddie Kadir. 114 Associate Professor Yvonne Hodgson Manager of Academic Programs and Quality, School of Biomedical Sciences. Convenor, Bachelor of Biomedical Sciences Dr Joanne Waring Student Services Manager Ms Natalie Seng Course Administrator Ms Leanne Sultana Student Services Officer supports the teaching activities within the School. These include the following School programs: the Bachelor of Biomedical Science, honours and four double degree courses, Bachelor of Radiography and Medical Imaging and postgraduate offerings in Medical Ultrasound, Nuclear Medicine and Radiation Therapy from the Department of Medical Imaging and Radiation Sciences, and the School’s involvement in the Bachelor of Science. Office staff are responsible for student selection, admission, enrolment and course completion. They are also available to help students manage the various challenges associated with University study. School Staff. From left to right: Mr Alan Hunter, Ms Vicki Burkitt, Ms Leanne Sultana, Associate Professor Yvonne Hodgson, Ms Jane McCausland, Ms Ico Ma, Ms Anne Sowersby, Ms Natalie Seng, Dr Joanne Waring, Dr Sharon Flecknoe and Mr Doug McGregor. Absent: Mr Kim Gan. Research Publications >> Papers >> Book chapters >> Reviews Annual Report 2011 Research Publications Number of publications Primary 385 Books, Book Chapters and Electronic Books 21 Reviews 31 Other 47 Total 484 Key: ANT Anatomy and Developmental Biology BCH Biochemistry and Molecular Biology IMM-C Immunology – Clayton MICRO Microbiology MISCL Monash Immunology and Stem Cell Laboratories MMI Monash Micro Imaging PHARM Pharmacology PHY Physiology RAD Medical Imaging and Radiation Sciences Primary Aitken, R.J., J.K. Findlay, K.J. Hutt, and J.B. Kerr, Apoptosis in the germ line. Reproduction, 2011. 141(2): p. 139-150 [ANT] Albiston, A.L., S. Diwakarla, R.N. Fernando, S.J. Mountford, H. Yeatman, B. Morgan, V. Pham, J.K. Holien, M.W. Parker, P.E. Thompson, and S.Y. Chai, Identification and development of specific inhibitors for insulin-regulated aminopeptidase as a new class of cognitive enhancers. Br J Pharmacol, 2011. 164(1): p. 37-47 [PHY] Alcock, F., C.T. Webb, P. Dolezal, V. Hewitt, M. Shingu-Vasquez, V.A. Likic, A. Traven, and T. Lithgow, A Small Tim Homohexamer in the Relict Mitochondrion of Cryptosporidium. Mol Biol Evol, 2011. E-pub: p. 113-122 [BCH] Al-Deen, F.N., J. Ho, C. Selomulya, C. Ma, and R. Coppel, Superparamagnetic Nanoparticles for Effective Delivery of Malaria DNA Vaccine. Langmuir, 2011. 27(7): p. 3703-3712 [MICRO] Ali, F., M.J. Rowley, B. Jayakrishnan, S. Teuber, M.E. Gershwin, and I.R. Mackay, Stiff-person Syndrome (SPS) and anti-GAD-related CNS Degenerations: Protean Additions to the Autoimmune Central Neuropathies. J Autoimm, 2011. 37: p. 79-87 [BCH] Alikhan, M.A., C.V. Jones, T.M. Williams, A.G. Beckhouse, A.L. Fletcher, M.M. Kett, S. Sakkal, C.S. Samuel, R.G. Ramsay, J.A. Deane, C.A. Wells, M.H. Little, D.A. Hume, and S.D. Ricardo, Colony-Stimulating Factor (CSF)-1 Promotes Kidney Growth and Repair via Alteration of Macrophage Responses. Am J Pathol, 2011. 179(3): p. 1243-1256 [MISCL,PHY,BCH] Alonzo III, F., B. Xayarath, J.C. Whisstock, and N.E. Freitag, Functional analysis of the Listeria monocytogenes secretion chaperone PrsA2 and its multiple contributions to bacterial virulence. Mol Microbiol, 2011. 80(6): p. 1530-1548 [BCH] Altuntas, A.O., B. Dagge, T.Y. Chin, J.E. Palamara, N. Eizenberg, R. Wolfe, and H.K. Graham, The effects of intramuscular tenotomy on the lengthening characteristics of tibialis posterior: high versus low intramuscular tenotomy. J Child Orthop, 2011. 5(3): p. 225-230 [ANT] Alvisi, G., O. Marin, G. Pari, M. Mancini, S. Avanzi, A. Loregian, D.A. Jans, and A. Ripalti, Multiple phosphorylation sites at the C-terminus regulate nuclear import of HCMV DNA polymerase processivity factor ppUL44. Virology, 2011. 417(2): p. 259-267 [BCH] 118 Ambaye, N.D., S. Pero, M.J. Gunzburg, M.Y. Yap, D.J. Clayton, M.P. Del Borgo, P. Perlmutter, M.I. Aguilar, G.S. Shukla, E. Peletskaya, M.M. Cookson, D.N. Krag, M.C. Wilce, and J.A. Wilce, Structural basis of binding by cyclic non-phosphorylated peptide antagonists of GRB7 implicated in breast cancer progression. J Mol Biol, 2011. 412(3): p. 397-411 [BCH] Ambrosini, Y.M., G.-X. Yang, W. Zhang, M. Tsuda, S. Shu, K. Tsuneyama, P.S.C. Leung, A.A. Ansari, R.L. Coppel, and M.E. Gershwin, The multi-hit hypothesis of primary biliary cirrhosis: polyinosinic-polycytidylic acid (poly I:C) and murine autoimmune cholangitis. Clin Exp Immunol, 2011. 166(1): p. 110-120 [MICRO] Amps, K., P.W. Andrews, G. Anyfantis, L. Armstrong, S. Avery, H. Baharvand, J. Baker, D. Baker, M.B. Munoz, S. Beil, N. Benvenisty, D. Ben-Yosef, J.C. Biancotti, A. Bosman, R.M. Brena, D. Brison, G. Caisander, M.V. Camarasa, J. Chen, E. Chiao, Y.M. Choi, A.B. Choo, D. Collins, A. Colman, J.M. Crook, G.Q. Daley, A. Dalton, P.A. De Sousa, C. Denning, J. Downie, P. Dvorak, K.D. Montgomery, A. Feki, A. Ford, V. Fox, A.M. Fraga, T. Frumkin, L. Ge, P.J. Gokhale, T. Golan-Lev, H. Gourabi, M. Gropp, L. Guangxiu, A. Hampl, K. Harron, L. Healy, W. Herath, F. Holm, O. Hovatta, J. Hyllner, M.S. Inamdar, A.K. Irwanto, T. Ishii, M. Jaconi, Y. Jin, S. Kimber, S. Kiselev, B.B. Knowles, O. Kopper, V. Kukharenko, A. Kuliev, M.A. Lagarkova, P.W. Laird, M. Lako, A.L. Laslett, N. Lavon, D.R. Lee, J.E. Lee, C. Li, L.S. Lim, T.E. Ludwig, Y. Ma, E. Maltby, I. Mateizel, Y. Mayshar, M. Mileikovsky, S.L. Minger, T. Miyazaki, S.Y. Moon, H. Moore, C. Mummery, A. Nagy, N. Nakatsuji, K. Narwani, S.K. Oh, C. Olson, T. Otonkoski, F. Pan, I.H. Park, S. Pells, M.F. Pera, L.V. Pereira, O. Qi, G.S. Raj, B. Reubinoff, A. Robins, P. Robson, J. Rossant, G.H. Salekdeh, T.C. Schulz, K. Sermon, J.S. Mohamed, H. Shen, E. Sherrer, K. Sidhu, S. Sivarajah, H. Skottman, C. Spits, G.N. Stacey, R. Strehl, N. Strelchenko, H. Suemori, B. Sun, R. Suuronen, K. Takahashi, T. Tuuri, P. Venu, Y. Verlinsky, D.W. Oostwaard, D.J. Weisenberger, Y. Wu, S. Yamanaka, L. Young and Q. Zhou, Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage. Nat Biotechnol, 2011. 29(12): p. 1132-1144 [ANT] Ang, C.S., J. Rothacker, H. Patsiouras, P. Gibbs, A.W. Burgess, and E.C. Nice, Use of multiple reaction monitoring for multiplex analysis of colorectal cancerassociated proteins in human feces. Electrophoresis, 2011. 32(15): p. 1926-1938 [BCH] Arumugam, T.V., Y.L. Cheng, Y. Choi, Y.H. Choi, S. Yang, Y.K. Yun, J.S. Park, D.K. Yang, J. Thundyil, M. Gelderblom, V.T. Karamyan, S.C. Tang, S.L. Chan, T. Magnus, C.G. Sobey, and D.G. Jo, Evidence that {gamma}-secretase-mediated Notch signaling induces neuronal cell death via the NF{kappa}B-Bim pathway in ischemic stroke. Mol Pharmacol, 2011. 80(1): p. 23-31 [PHARM] Astle, M.V., L.M. Ooms, A.R. Cole, L.C. Binge, J.M. Dyson, M.J. Layton, S. Petratos, C. Sutherland, and C.A. Mitchell, Identification of a proline-rich inositol polyphosphate 5-phosphatase (PIPP): collapsin response mediator protein 2 (CRMP2) complex that regulates neurite elongation. J Biol Chem, 2011. 286(26): p. 23407-23418 [BCH] Aurelio, L., A. Christopoulos, B.L. Flynn, P.J. Scammells, P.M. Sexton, and C. Valant, The synthesis and biological evaluation of 2-amino4,5,6,7,8,9-hexahydrocycloocta[b]thiophenes as allosteric modulators of the A(1) adenosine receptor. Bioorg Med Chem Lett, 2011. 21(12): p. 3704-3707 [PHARM] Aydin, I., A. Dimitropoulos, S.H. Chen, C. Thomas, and A. Roujeinikova, Purification, crystallization and preliminary X-ray crystallographic analysis of the putative Vibrio parahaemolyticus resuscitationpromoting factor YeaZ. ACTA Crystall F, 2011. F67(5): p. 604-607 [BCH,MICRO] Aydin, I., Y. Saijo-Hamano, K. Namba, C. Thomas, and A. Roujeinikova, Structural Analysis of the Essential Resuscitation Promoting Factor YeaZ Suggests a Mechanism of Nucleotide Regulation through Dimer Reorganization. PLoS One, 2011. 6(8): p. e23245 [MICRO,BCH] Bach, M., M. Larance, D.E. James, and G. Ramm, The Serine/Threonine Kinase ULK1 is a target of multiple phosphorylation events. Biochem J, 2011. 440(2): p. 283-291 [BCH,MMI] Balamatsias, D., A.M. Kong, J.E. Waters, A. Sriratana, R. Gurung, C.G. Bailey, J.E. Rasko, T. Tiganis, S.L. Macaulay, and C.A. Mitchell, Identification of P-Rex1 as a novel Rac1-guanine nucleotide exchange factor (GEF) that promotes actin remodelling and GLUT4 trafficking in adipocytes. J Biol Chem, 2011. 286(50): p. 43229-43240 [BCH] Bannam, T.L., X.X. Yan, P.F. Harrison, T. Seemann, A.L. Keyburn, C. Stubenrauch, L.H. Weeramantri, J.K. Cheung, B.A. McClane, J.D. Boyce, R.J. Moore, and J.I. Rood, Necrotic enteritis-derived Clostridium perfringens strain with three closely related independently conjugative toxin and antibiotic resistance plasmids. MBio, 2011. 2(5): p. e00190-11 [MICRO] Becker, T., L.S. Wenz, V. Kruger, W. Lehmann, J.M. Muller, L. Goroncy, N. Zufall, T. Lithgow, B. Guiard, A. Chacinska, R. Wagner, C. Meisinger, and N. Pfanner, The mitochondrial import protein Mim1 promotes biogenesis of multispanning outer membrane proteins. J Cell Biol, 2011. 194(3): p. 387-395 [BCH] Beeman, S.C., M. Zhang, L. Gubhaju, T. Wu, J.F. Bertram, D.H. Frakes, B.R. Cherry, and K.M. Bennett, Measuring glomerular number and size in perfused kidneys using MRI. Am J Physiol Renal Physiol, 2011. 300(6): p. F1454-F1457 [ANT] Beltran, M.A., D.M. Paganin, K.K. Siu, A. Fouras, S.B. Hooper, D.H. Reser, and M.J. Kitchen, Interfacespecific x-ray phase retrieval tomography of complex biological organs. Phys Med Biol, 2011. 56(23): p. 7353-7369 [PHY] Benziane, B., U. Widegren, S. Pirkmajer, J. Henriksson, N.K. Stepto, and A.V. Chibalin, Effect of exercise and training on phospholemman phosphorylation in human skeletal muscle. Am J Physiol Endocrinol Metab, 2011. 96(1): p. E48-E56 [PHY] Berry, R., Z. Chen, J. McCluskey, and J. Rossjohn, Insight into the basis of autonomous immunoreceptor activation. Trends Immunol, 2011. 32(4): p. 165-170 [BCH] Bertucci, M.C., J.M. Loose, E.M. Wallace, G. Jenkin, and S.L. Miller, Anti-inflammatory therapy in an ovine model of fetal hypoxia induced by single umbilical artery ligation. Reprod Fertil Dev, 2011. 23(2): p. 346352 [PHY] Bettaieb, A., S. Liu, Y. Xi, N. Nagata, K. Matsuo, I. Matsuo, S. Chahed, J. Bakke, H. Keilhack, T. Tiganis, and F.G. Haj, Differential regulation of endoplasmic reticulum stress by protein tyrosine phosphatase 1B and T cell protein tyrosine phosphatase. J Biol Chem, 2011. 286(11): p. 9225-9235 [BCH] Bharadwaj, M., P. Illing, A. Theodossis, A.W. Purcell, J. Rossjohn, and J. McCluskey, Drug Hypersensitivity and Human Leukocyte Antigens of the Major Histocompatibility Complex. Annu Rev Pharmacol Toxicol, 2011. E-pub: p. 401-431 [BCH] Bird, A.D., S.J. Flecknoe, K.H. Tan, P.F. Olsson, N. Antony, T. Mantamadiotis, S.B. Hooper, and T.J. Cole, cAMP Response Element Binding Protein Is Required for Differentiation of Respiratory Epithelium during Murine Development. PLoS One, 2011. 6(3): p. e17843 [BCH] Boerboom, D., J.F. Lafond, X. Zheng, E. Lapointe, L. Mittaz, A. Boyer, M.A. Pritchard, F.J. Demayo, J.S. Mort, R. Drolet, and J.S. Richards, Partially redundant functions of Adamts1 and Adamts4 in the perinatal development of the renal medulla. Dev Dyn, 2011. 240(7): p. 1806-1814 [BCH] Borg, M.L., Z.B. Andrews, E.J. Duh, R. Zechner, P.J. Meikle, and M.J. Watt, Pigment Epithelium-Derived Factor Regulates Lipid Metabolism via Adipose Triglyceride Lipase. Diabetes, 2011. 60(5): p. 14581466 [PHY] Bosnyak, S., E. Jones, A. Christopoulos, M.I. Aguilar, W. Thomas, and R. Widdop, Relative affinity of angiotensin peptides and novel ligands at AT1 and AT2 receptors. Clin Sci (Lond), 2011. 121(7): p. 297303 [PHARM,BCH] Botte, C.Y., Y. Yamaryo-Botte, J. Janouskovec, T. Rupasinghe, P.J. Keeling, P. Crellin, R. Coppel, E. Marechal, M.J. McConville, and G.I. McFadden, Identification of plant-like galactolipids in Chromera velia, a photosynthetic relative of malaria parasites. J Biol Chem, 2011. 286(34): p. 29893-29903 [MICRO] Bottomley, S.P., The structural diversity in alpha(1)antitrypsin misfolding. EMBO Rep, 2011. 12(10): p. 983-984 [BCH] Brait, V.H., J. Rivera, B.R. Broughton, S. Lee, G.R. Drummond, and C.G. Sobey, Chemokine-related gene expression in the brain following ischemic stroke: No role for CXCR2 in outcome. Brain Res, 2011. 1372: p. 169-179 [PHARM] Brennan, A.J., J. Chia, K.A. Browne, A. Ciccone, S. Ellis, J.A. Lopez, O. Susanto, S. Verschoor, H. Yagita, J.C. Whisstock, J.A. Trapani, and I. Voskoboinik, Protection from endogenous perforin: glycans and the C terminus regulate exocytic trafficking in cytotoxic lymphocytes. Immunity, 2011. 34(6): p. 879-892 [BCH] Brew, N., S.B. Hooper, B.J. Allison, M.J. Wallace, and R. Harding, Injury and repair in the very immature lung following brief mechanical ventilation. Am J Physiol Lung Cell Mol Physiol, 2011. 301(6): p. L917-L926 [ANT] Briggs, D.I. and Z.B. Andrews, Metabolic Status Regulates Ghrelin Function on Energy Homeostasis. Neuroendocrinology, 2011. 93(1): p. 48-57 [PHY] Briggs, D.I. and Z.B. Andrews, A Recent Update on the Role of Ghrelin in Glucose Homeostasis. Curr Diabetes Rev, 2011. 7(3): p. 201-207 [PHY] Briggs, D.I., M.B. Lemus, E. Kua, and Z.B. Andrews, Diet-induced obesity attenuates fasting-induced hyperphagia. J Neuroendocrinol, 2011. 23(7): p. 620626 [PHY] Brown, R.D., L.M. Hilliard, G.A. Head, E.S. Jones, R.E. Widdop, and K.M. Denton, Sex Differences in the Pressor and Tubuloglomerular Feedback Response to Angiotensin II. Hypertension, 2011. E-pub: p. 129-135 [PHY,PHARM] Brown, R.D., A.J. Turner, M. Carlstrom, A.E. Persson, and K.J. Gibson, Tubuloglomerular feedback response in the prenatal and postnatal ovine kidney. Am J Physiol Renal Physiol, 2011. 300(6): p. F1368-F1374 [PHY] Buckle, A.M., M.A. Bate, S. Androulakis, M. Cinquanta, J. Basquin, F. Bonneau, D.K. Chatterjee, D. Cittaro, S. Graslund, A. Gruszka, R. Page, S. Suppmann, J.X. Wheeler, D. Agostini, M. Taussig, C.F. Taylor, S.P. Bottomley, A. Villaverde, and A. de Marco, Recombinant protein quality evaluation: proposal for a minimal information standard. Stand Genomic Sci, 2011. 5(2): p. 195-197 [BCH] Bulfin, L.J., M.A. Clarke, K.M. Buller, and S.J. Spencer, Anxiety and hypothalamic-pituitary-adrenal axis responses to psychological stress are attenuated in male rats made lean by large litter rearing. Psychoneuroendocrinology, 2011. 36(7): p. 10801091 [PHY] Bullen, M.L., A.A. Miller, J. Dharmarajah, G.R. Drummond, C.G. Sobey, and B.K. Kemp-Harper, Vasorelaxant and anti-aggregatory actions of the nitroxyl donor, isopropylamine NONOate, are maintained in hypercholesterolemia. Am J Physiol Heart Circ Physiol, 2011. 301(4): p. H1405-H1414 [PHARM] Burke, S.L., R.G. Evans, and G.A. Head, Effects of chronic sympatho-inhibition on renal excretory function in renovascular hypertension. J Hypertens, 2011. 29(5): p. 945-952 [PHY,PHARM] Burman, K.J., D.H. Reser, K.E. Richardson, H. Gaulke, K.H. Worthy, and M.G. Rosa, Subcortical projections to the frontal pole in the marmoset monkey. Eur J Neurosci, 2011. 34(2): p. 303-319 [PHY] Calder, A.E., M.N. Hince, J.A. Dudakov, A.P. Chidgey, and R.L. 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Pearson, AKT promotes rRNA synthesis and cooperates with c-MYC to stimulate ribosome biogenesis in cancer. Sci Signal, 2011. 4(188): p. ra56 [BCH] Chen, H.Y., X.R. Huang, W. Wang, J.H. Li, R.L. Heuchel, A.C. Chung, and H.Y. Lan, The protective role of smad7 in diabetic kidney disease: mechanism and therapeutic potential. Diabetes, 2011. 60(2): p. 590-601 [ANT] Colwill, K., H. Persson, N.E. Jarvik, A. Wyrzucki, J. Wojcik, A. Koide, A.A. Kossiakoff, S. Koide, S. Sidhu, M.R. Dyson, K. Pershad, J.D. Pavlovic, A. KarattVellatt, D.J. Schofield, B.K. Kay, J. McCafferty, M. Mersmann, D. Meier, J. Mersmann, S. Helmsing, M. Hust, S. Dubel, S. Berkowicz, A. Freemantle, M. Spiegel, A. Sawyer, D. Layton, E. Nice, A. Dai, O. Rocks, K. Williton, F.A. Fellouse, K. Hersi, T. Pawson, P. Nilsson, M. Sundberg, R. Sjoberg, A. Sivertsson, J.M. Schwenk, J.O. Takanen, S. Hober, M. Uhlen, L.G. Dahlgren, A. Flores, I. Johansson, J. Weigelt, L. Crombet, P. Loppnau, I. Kozieradzki, D. Cossar, C.H. 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Pearson, Elevated vascular resistance and afterload reduce the cardiac output response to dobutamine in early growthrestricted rats in adulthood. Br J Nutr, 2011. 106(9): p. 1374-1382 [ANT,PHY] Reviews Drummond, G.R., S. Selemidis, K.K. Griendling, and C.G. Sobey, Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets. Nat Rev Drug Discov, 2011. 10(6): p. 453-471 [PHARM] Fulcher, A.J. and D.A. Jans, Regulation of nucleocytoplasmic trafficking of viral proteins: An integral role in pathogenesis? Biochim Biophys Acta, 2011. 1813(12): p. 2176-2190 [BCH] Godfrey, D.I. and J. Rossjohn, New ways to turn on NKT cells. J Exp Med, 2011. 208(6): p. 1121-1125 [BCH] Gras, S., L. Kjer-Nielsen, Z. Chen, J. Rossjohn, and J. McCluskey, The structural bases of direct T-cell allorecognition: implications for T-cell-mediated transplant rejection. Immunol Cell Biol, 2011. 89(3): p. 388-395 [BCH] Harper, M., A.D. Cox, B. Adler, and J.D. Boyce, Pasteurella multocida lipopolysaccharide: The long and the short of it. Vet Microbiol, 2011. 153(1-2): p. 109-115 [MICRO] He, Z., A.J. Vingrys, J.A. Armitage, and B.V. Bui, The role of blood pressure in glaucoma. Clin Exp Optom, 2011. 94(2): p. 133-149 [ANT] Kennan, R.M., X. Han, C.J. Porter, and J.I. Rood, The pathogenesis of ovine footrot. Vet Microbiol, 2011. 153(1-2): p. 59-66 [MICRO,BCH] Koppers, A.J., T. Reddy, and M.K. O'Bryan, The role of cysteine-rich secretory proteins in male fertility. Asian J Androl, 2011. 13(1): p. 111-117 [ANT] Kranich, J., K.M. Maslowski, and C.R. Mackay, Commensal flora and the regulation of inflammatory and autoimmune responses. Semin Immunol, 2011. 23(2): p. 139-145 [IMM-C] Actis, G.C., F. Rosina, and I.R. Mackay, Inflammatory bowel disease: beyond the boundaries of the bowel. Expert Rev Gastroenterol Hepatol, 2011. 5(3): p. 401410 [BCH] Lee, A.B., D. Nandurkar, M.E. Schneider-Kolsky, M. Crossett, S.K. Seneviratne, J.D. Cameron, and J.M. Troupis, Coronary Image Quality of 320-MDCT in Patients With Heart Rates Above 65 Beats per Minute: Preliminary Experience. AJR Am J Roentgenol, 2011. 196(6): p. W729-W735 [RAD] Adler, B., M. Lo, T. Seemann, and G.L. Murray, Pathogenesis of leptospirosis: The influence of genomics. Vet Microbiol, 2011. 153(1-2): p. 73-81 [MICRO] Mijaljica, D., M. Prescott, and R.J. Devenish, Microautophagy in mammalian cells: Revisiting a 40-year-old conundrum. Autophagy, 2011. 7(7): p. 673-682 [BCH] Aitken, R.J. and A.J. Koppers, Apoptosis and DNA damage in human spermatozoa. Asian J Androl, 2011. 13(1): p. 36-42 [ANT] Quenault, T., T. Lithgow, and A. Traven, PUF proteins: repression, activation and mRNA localization. Trends Cell Biol, 2011. 21(2): p. 104-112 [BCH] Allwood, E.M., R.J. Devenish, M. Prescott, B. Adler, and J.D. Boyce, Strategies for Intracellular Survival of Burkholderia pseudomallei. Front Microbiol, 2011. 2(170): p. 1-19 [BCH,MICRO] Selmi, C., C.L. Bowlus, M.E. Gershwin, and R.L. Coppel, Primary biliary cirrhosis. Lancet, 2011. 377(9777): p. 1600-1609 [MICRO] Andrews, Z.B., The extra-hypothalamic actions of ghrelin on neuronal function. Trends Neurosci, 2011. 34(1): p. 31-40 [PHY] Andrews, Z.B., Central mechanisms involved in the orexigenic actions of ghrelin. Peptides, 2011. 32(11): p. 1-8 [PHY] Archbold, J.K., J.U. Flanagan, H.A. Watkins, J.J. Gingell, and D.L. Hay, Structural insights into RAMP modification of secretin family G protein-coupled receptors: implications for drug development. Trends Pharmacol Sci, 2011. 32(10): p. 591-600 [BCH] Baker, J.G., S.J. Hill, and R.J. Summers, Evolution of beta-blockers: from anti-anginal drugs to liganddirected signalling. Trends Pharmacol Sci, 2011. 32(4): p. 227-234 [PHARM] Bertram, J.F., R.N. Douglas-Denton, B. Diouf, M.D. Hughson, and W.E. Hoy, Human nephron number: implications for health and disease. Pediatr Nephrol, 2011. 26(9): p. 1529-1533 [ANT] Campbell, B.E., P.R. Boag, A. Hofmann, C. Cantacessi, C.K. Wang, P. Taylor, M. Hu, Z.U. Sindhu, A. Loukas, P.W. Sternberg, and R.B. Gasser, Atypical (RIO) protein kinases from Haemonchus contortus - Promise as new targets for nematocidal drugs. Biotechnol Adv, 2011. 29(3): p. 338-350 [BCH] Canals, M., P.M. Sexton, and A. Christopoulos, Allostery in GPCRs: 'MWC' revisited. Trends Biochem Sci, 2011. 36(12): p. 663-672 [PHARM] Shingu-Vazquez, M. and A. Traven, Mitochondria and fungal pathogenesis: drug tolerance, virulence and potential for antifungal therapy. Eukaryot Cell, 2011. 10(11): p. 1376-1383 [BCH] Song, J., H. Tan, S.E. Boyd, H. Shen, K. Mahmood, G.I. Webb, T. Akutsu, J.C. Whisstock, and R.N. Pike, Bioinformatic approaches for predicting substrates of proteases. J Bioinform Comput Biol, 2011. 9(1): p. 149-78 [BCH] Spencer, S.J., M.A. Galic, and Q.J. Pittman, Neonatal programming of innate immune function. Am J Physiol Endocrinol Metab, 2011. 300(1): p. E11-E18 [PHY] Stewart, S.E., M.E. D'Angelo, and P.I. Bird, Intercellular communication via the endo-lysosomal system: Translocation of granzymes through membrane barriers. Biochim Biophys Acta, 2011. E-pub: p. 59-67 [BCH] Tiganis, T., Reactive oxygen species and insulin resistance: the good, the bad and the ugly. Trends Pharmacol Sci, 2011. 32(2): p. 82-89 [BCH] Books, Book Chapters, Electronic Books and CD Roms Bayliss, J., R. Stark, A. Reichenbach, and Z.B. Andrews, Gut Hormones restrict neurodegeneration in Parkinson's Disease, in Advanced Understanding of Neurodegenerative Diseases, R.C.-C. Chang, Editor. 2011, InTech: Croatia. p. 269-284 [PHY] Beilharz, T.H. and T. Preiss, Polyadenylation State Microarray (PASTA) Analysis, in Methods Mol Biol - Yeast Systems Biology, J. Castrillo and S. Oliver, Editors. 2011, Humana Press: USA. p. 133-148 [BCH] Beinrohr, L., T.A. Murray-Rust, L. Dyksterhuis, P. Zavodszky, P. Gal, R.N. Pike, and L.C. Wijeyewickrema, Serpins and the complement system, in Methods Enzymol, P. Bird and J. Whisstock, Editors. 2011, Academic Press Elsevier Inc: UK. p. 55-75 [BCH] Black, M.J., M.R. Sutherland, and L. Gubhaju, Effects of Preterm Birth on the Kidney, in Basic Nephrology and Acute Kidney Injury, M. Sahay, Editor. 2011, InTech: India. p. 61-88 [ANT] Chidgey, A.P., N. Seach, R. Lim, and R.L. Boyd, Stem Cells and Regenerative Medicine - The Evolving Story, in Stem Cell Technologies, S. Totey and K. Deb, Editors. 2011, Tata McGraw-Hill Education Private Limited: USA. p. 1-18 [MISCL] Mackay, I.R., Gastrointestinal: Liver, in Systemic Lupus Erythematosus, G.T. RG Lahita, JP Buyon, T Koike, Editor. 2011, Academic Press (Elsevier): UK. p. 865-886 [BCH] Mijaljica, D., C.J. Rosado, R.J. Devenish, and M. Prescott, Biosensors for monitoring autophagy, in Biosensors - Emerging Materials and Applications, P. Serra, Editor. 2011, InTech: Croatia. p. 383-400 [BCH] Pearce, M.C. and L.D. Cabrita, Production of Recombinant Serpins in Escherichia coli, in Methods Enzymol, P. Bird and J. Whisstock, Editors. 2011, Academic Press: USA. p. 13-28 [BCH] Phan, J., N. Yamout, J. Schmidberger, S.P. Bottomley, and A.M. Buckle, Refolding Your Protein with a Little Help from REFOLD, in Methods Mol Biol, K.B. AF Hill, SP Bottomley and R Cappai, Editor. 2011, Humana Press: UK. p. 45-57 [BCH] Song, J., A.Y. Matthews, C.F. Reboul, D. Kaiserman, R.N. Pike, P.I. Bird, and J.C. Whisstock, Predicting serpin/protease interactions, in Methods Enzymol, PI Bird and J. Whisstock, Editors. 2011, Academic Press: USA. p. 237-273 [BCH] Yongqing, T., J. Potempa, R.N. Pike, and L.C. Wijeyewickrema, The lysine-specific gingipain of porphyromonas gingivalis : importance to pathogenicity and potential strategies for inhibition, in Adv Exp Med Biol - Cystein Proteases of Pathogenic Organisms, M.R.a.J. Dalton, Editor. 2011, Springer Science + Business Media, LLC Landes Biosciences: USA. p. 15-29 [BCH] Dunstone, M.A. and J.C. Whisstock, Crystallography of serpins and serpin complexes, in Methods Enzymol, P. Bird and J. Whisstock, Editors. 2011, Academic Press: USA. p. 63-87 [BCH] Other publications Furic, L., M. Livingstone, I. Topisirovic, and N. Sonenberg, Actions of Insulin As a Survival and Growth Factor: Akt, mTOR, and Regulation of Translation, in Insulin Resistance and Cancer Epidemiology, Cellular and Molecular Mechanisms and Clinical Implications, I. Fantus, Editor. 2011, Springer Science + Business Media LLC: USA. p. 181-192 [ANT] Richards, M., J. Knox, B. Elliott, K. Mackin, D. Lyras, L.J. Waring, and T.V. Riley, Severe infection with Clostridium difficile PCR ribotype 027 acquired in Melbourne, Australia. Med J Aust, 2011. 194(7): p. 369-371 [MICRO] Grassinger, J. and S.K. Nilsson, Methods to analyze the homing efficiency and spatial distribution of hematopoietic stem and progenitor cells and their relationship to the bone marrow endosteum and vascular endothelium, in Methods Mol Biol - Stem Cell Migration, M.-D. Filippi and H. Geiger, Editors. 2011, Springer Science + Business Media, LLC 2011: USA. p. 197-214 [ANT] Cases Clinical Samarawickrema, N.A., S.N. Tabrizi, J. Hewavisenthi, T. Leong, and S.M. Garland, Distribution of human papillomavirus genotypes in archival cervical tissue from women with cervical cancer in urban Sri Lanka. Int J Gynaecol Obstet, 2011. 115(2): p. 180-182 [BCH] Communications Grigoryev, S. and S. McGowan, Isolation and Characterization of the Nuclear Serpin MENT, in Methods Enzymol, P. Bird and J. Whisstock, Editors. 2011, Academic Press: USA. p. 29-47 [BCH] Brown, K.A., K.J. McInnes, K. Takagi, K. Ono, N.I. Hunger, L. Wang, H. Sasano, and E.R. Simpson, LKB1 expression is inhibited by estradiol-17beta in MCF-7 cells. J Steroid Biochem Mol Biol, 2011. 127(3-5): p. 1-5 [PHY,BCH] Ho, M.S., A. Fryga, and A.L. Laslett, Flow cytometric analysis of human pluripotent stem cells, in Methods Mol Biol, P. Schwartz and R. Wesselschmidt, Editors. 2011, Springer Science + Business Media, LLC: USA. p. 221-230 [ANT] Cronin, C., T.M. Edwards, and M.E. Gibbs, Role for purinergic receptors in memory processing in young chicks. Behav Brain Res, 2011. 223(2): p. 417-420 [ANT] Horvath, A.J., B.G. Lu, R.N. Pike, and S.P. Bottomley, Methods to measure the kinetics of protease inhibition by serpins, in Methods Enzymol, P. Bird and J. Whisstock, Editors. 2011, Academic Press USA. p. 223-235 [BCH] Hou, X., D.H. Small, and M.I. Aguilar, Surface plasmon resonance spectroscopy: a new lead in studying the membrane binding of amyloidogenic transthyretin, in Methods Mol Biol, K.B. AF Hill, SP Bottomley, and R. Cappai, Editors. 2011, Springer Science + Business Media, LLC: USA. p. 215-228 [BCH] Kaiserman, D., C. Hitchen, V. Levina, S.P. Bottomley, and P.I. Bird, Intracellular production of recombinant serpins in yeast, in Methods Enzymol, P. Bird and J. Whisstock, Editors. 2011, Academic Press: USA. p. 1-12 [BCH] Kass, I., C.F. Reboul, and A.M. Buckle, Computational methods for studying serpin conformational change and structural plasticity, in Methods Enzymol, P. Bird and J. Whisstock, Editors. 2011, Academic Press: USA. p. 295-323 [BCH] Kouspou, M.M. and J.T. Price, Analysis of cellular migration using a two-chamber methodology, in Methods Mol Biol - Molecular Chaperones, S. Calderwood and T. Prince, Editors. 2011, Springer Science+business Media, LLC 2011: USA. p. 303-317 [BCH] Elliott, D.A., S.R. Braam, K. Koutsis, E.S. Ng, R. Jenny, E.L. Lagerqvist, C. Biben, T. Hatzistavrou, C.E. Hirst, Q.C. Yu, R.J. Skelton, D. Ward-van Oostwaard, S.M. Lim, O. Khammy, X. Li, S.M. Hawes, R.P. Davis, A.L. Goulburn, R. Passier, O.W. Prall, J.M. Haynes, C.W. Pouton, D.M. Kaye, C.L. Mummery, A.G. Elefanty, and E.G. Stanley, NKX2-5eGFP/w hESCs for isolation of human cardiac progenitors and cardiomyocytes. Nat Methods, 2011. 8(12): p. 10371040 [MISCL] Qi, T., K. Ly, D.R. Poyner, G. Christopoulos, P.M. Sexton, and D.L. Hay, Structure-function analysis of amino acid 74 of human RAMP1 and RAMP3 and its role in peptide interactions with adrenomedullin and calcitonin gene-related peptide receptors. Peptides, 2011. 32(5): p. 1060-1067 [PHARM] Telwatte, S., K. Moore, A. Johnson, D. Tyssen, J. Sterjovski, M. Aldunate, P.R. Gorry, P.A. Ramsland, G.R. Lewis, J.R. Paull, S. Sonza, and G. Tachedjian, Virucidal activity of the dendrimer microbicide SPL7013 against HIV-1. Antiviral Res, 2011. 90(3): p. 195-199 [MICRO] Verghese, E., J. Zhuang, D. Saiti, S.D. Ricardo, and J.A. Deane, In vitro investigation of renal epithelial injury suggests that primary cilium length is regulated by hypoxia-inducible mechanisms. Cell Biol Int, 2011. 35(9): p. 909-913 [MISCL] Conference Papers Kamada, M., M. Hayashida, J. Song, and T. Akutsu, Discriminative Random Field Approach to Prediction of Protein Residue Contacts, in The 4th International Conference on Computational Systems Biology (ISB2010), X.-S.Z. L Chen, Y Wang, Editor. 2011, IEEE: Zhuhai, China. p. 285-291 [BCH]. Wang, M., H.-B. Shen, T. Akutsu, and J. Song, Predicting functional impact of single amino acid polymorphisms by integrating sequence and structural features, in The 4th International Conference on Computational Systems Biology (ISB2010), X.-S.Z. L Chen, Y Wang, Editor. 2011, IEEE: Zhuhai, China. p. 18-26 [BCH]. Xu, K.-J., F.-Y. Hu, J. Song, and X.-M. Zhao, Exploring drug combinations in a drug-cocktail network, in 2011 IEEE Conference on Systems Biology (ISB2010), X.-S.Z. L Chen, Y Wang, Editor. 2011, IEEE: Zhuhai, China. p. 393-398 [BCH]. Editorials Carter, G.P., M.M. Awad, M.L. Kelly, J.I. Rood, and D. Lyras, TcdB or not TcdB: a tale of two Clostridium difficile toxins. Future Microbiol, 2011. 6(2): p. 121-123 [MICRO] Denton, K.M., The renin-angiotensin system: new horizons. J Hypertens, 2011. 29(10): p. 1857-1858 [PHY] Devenish, R.J., Autophagy and the evasion of host defense: A new variation on the theme for Burkholderia cepacia? Autophagy, 2011. 7(11) p. 1269-1270 [BCH] Evans, R.G. and D.F. Su, Data presentation and use of statistical tests in biomedical journals: can we reach a consensus? Clin Exp Pharmacol Physiol, 2011. 38(5): p. 285-286 [PHY] Kemp-Harper, B.K., Nitroxyl (HNO): a novel redox signaling molecule. Antioxid Redox Signal, 2011. 14(9): p. 1-5 [PHARM] Prescott, M., Autophagy - Recycling for a Healthy Lifestyle. Australian Biochemist, 2011. 42(2): p. 3-4 [BCH] Letter to the Editor Chuang, M.-S.K., B.J. Canny, and P.G. McMenamin, Should there be a national core curriculum for anatomy? ANZ J Surg, 2011. 81(12): p. 950 [ANT] News: Commentary and Comments Beddoe, T., A.G. Brooks, and J. Rossjohn, How opposites attract. Immunol Cell Biol, 2011. 89(2): p. 1-2 [BCH] Britt, K. and R. Short, The plight of nuns: hazards of nulliparity. Lancet, 2011. E-pub: p. 1-2 [ANT] Loveland, K.L., Defining the Impact of Estrogen on Spermatogonial Fate. Biol Reprod, 2011. 85(4): p. 648-649 [BCH,ANT] Maslowski, K.M. and C.R. Mackay, Diet, gut microbiota and immune responses. Nat Immunol, 2011. 12(1): p. 5-9 [IMM-C] Mijaljica, D., M. Prescott, and R.J. Devenish, V-ATPase engagement in autophagic processes. Autophagy, 2011. 7(6): p. 666-668 [BCH] Rossjohn, J., New cell type offers new hope. Monash University - News and Events, 2011: p. 1-2 [BCH] Newsletters & Magazines Bach, M. and G. Ramm, How to control self-eating habits: Metabolic control of autophagy. Australian Biochemist, 2011. 42(2): p. 17-20 [BCH,MMI] D'Cruze, T. and R.J. Devenish, Autophagy as a defence mechanism against bacterial pathogens. Australian Biochemist, 2011. 42(2): p. 11-13 [BCH] Mackay, I.R., Recollections on Beginnings - of ASI and of ASCIA. ASI Newsletter, 2011. September 2011: p. 1-4 [BCH] May, A. and M. Prescott, Hungry for Power: Elimination of mitochondria by mitophagy. Australian Biochemist, 2011. 42(2): p. 4-7[BCH] Nagley, P., History of Biochemistry and Molecular Biology at Monash University: Part 2 (1992-2011). Australian Biochemist, 2011. 42: p. 36-42 [BCH] 127 Research Staff Index A G Gabriel, Dr Kip P Abud, Dr Helen 28 Adler, Professor Ben 53 Parkington, Associate Professor Helena 66 Pike, Professor Robert 52 Aguilar, Associate Professor Mibel 78 H Andrews, Dr Zane 72 Harding, Professor Richard 31 Price, Dr John 18 Price, Dr Nicholas Armitage, Dr James 28 Henry, Dr Belinda 67 73 Prescott, Dr Mark 83 39 Pritchard, Dr Melanie 35 J R Jans, Professor David 56 Rajan, Associate Professor Ramesh 67 Ricardo, Associate Professor Sharon 49 K Risbridger, Professor Gail 19 Kett, Dr Michelle 22 Rood, Professor Julian 58 14 Rosa, Professor Marcello 65 Rossjohn, Professor Jamie 84 Roujeinikova, Associate Professor Anna 59 Hodgson, Professor Wayne B 55 Bernard, Professor Claude 46 Bertram, Professsor John 29 Beddoe, Associate Professor Travis 78 Bird, Professor Phillip 52 Black, Associate Professor Mary Jane 29 Boag, Dr Peter 30 Borg, Dr Natalie 79 Bottomley, Professor Stephen 79 Boyce, Dr John 53 Lackmann, Associate Professor Martin 15 Boyd, Professor Richard 47 Lang, Dr Richard 66 S Buckle, Associate Professor Ashley 80 Lawen, Dr Alfons 14 Schneider-Kolsky, Dr Michal 61 Burman, Dr Kathleen 64 31 Sexton, Professor Patrick 38 Bunnett, Professor Nigel 38 56 Smith, Professor Ian 23 Loveland, Professor Kate 32 Smith, Dr Jeremy T 68 Lyras, Dr Dena 57 C Chidgey, Associate Professor Ann Christopoulos, Professor Arthur Kwok-Schuelein, Dr Terry L Li, Dr Jinhua Lithgow, Professor Trevor Smyth, Dr Ian 35 47 Sobey, Associate Professor Chris 24 38 Spencer, Dr Sarah J 74 Stanley, Professor Ed 48 Summers, Professor Roger 38 Clarke, Professor Iain 64 Clements, Dr Craig Cole, Associate Professor Timothy M Mackay, Professor Charles 42 80 McGowan, Dr Sheena 82 30 McMenamin, Professor Paul 33 Coleman, Dr Harold 66 Meeusen, Professor Els 57 T Cooke, Professor Brian 54 Mitchell, Professor Christina 16 Tare, Dr Marianne 66 Coulibaly, Dr Fasseli 81 Tiganis, Professor Tony 18 Cowley, Professor Michael 72 Tilbrook, Professor Alan 68 Traven, Dr Ana 59 D N Nagley, Professor Phillip 17 Netter, Associate Professor Hans 58 Nice, Professor Ed 17 W Davies, Professor John 54 Denton, Associate Professor Kate 22 Watt, Associate Professor Matthew 74 Devenish, Professor Rod 55 Whisstock, Professor James 85 Drummond, Dr Grant 24 Widdop, Professor Robert 25 Dunstone, Dr Michelle 82 Wilce, Associate Professor Jackie 83 Wilce, Professor Matthew 83 E O O’Bryan, Professor Moira 34 Oldfield, Professor Brian 73 Elefanty, Professor Andrew 48 Y Elliott, Professor David 49 Yu, Dr Di Evans, Associate Professor Roger 22 43 Further information School of Biomedical Sciences Building 77 Monash University Clayton, VIC 3800 Australia Telephone: +61 3 9902 9407 Email: vicki.burkitt@monash.edu twitter.com/Monash_FMNHS www.med.monash.edu/sobs Monash University reserves the right to alter information, procedures, fees and regulations contained in this document. 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