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The John Curtin School of Medical Research The John Curtin School of Medical Research From the Director This year marks 60 years since the foundation of The John Curtin School of Medical Research (JCSMR) as part of The Australian National University (ANU) in 1948. JCSMR is the result of the vision of Australian Nobel Laureate Sir Howard Florey and war-time Prime Minister John Curtin. Florey foresaw a national medical research school where scientists would carry out superlative research in fundamental areas, and our staff and students continue to strive towards this goal. A major strength of our research programs lies in their strong cross-disciplinary interactions. We currently have strong programs in genomics and epigenomics, immunology, protein structure and function and cell signalling, virology and neuroscience. This research aims to understand and provide novel insights into diseases such as cancer, diabetes and rheumatoid arthritis, and conditions such as epilepsy and vision impairment, amongst others. Our research staff continue to perform at the highest level nationally and internationally. This report highlights some of our recent research findings that will have impact on human health. Many of our staff and students have received recognition for their contributions through prizes and awards. As an integral part of the ANU College of Medicine, Biology and Environment, we are committed to cross-disciplinary research that will provide solutions to health problems which beset our community, and we continue to pride ourselves on our commitment to the training and mentoring of the young medical researchers of the future. Professor Frances Shannon Director JCSMR The John Curtin School of Medical Research Annual Review 2008 1 Table of Contents Introduction to The John Curtin School of Medical Research From the Director. .1 Selected Highlights. 3 Jackie Chan Science Centre . 6 JCSMR Structure. 7 Boards and Committees . 8 Research Programs . .9 Division of Immunology and Genetics. .10 Division of Molecular Bioscience. .18 Division of Neuroscience. 28 High Blood Pressure Research Unit. .33 Staff & Student Achievements . 35 Degrees . .36 Prizes and awards . .37 Research Collaborations & Visitors . .39 Visitors to JCSMR. 40 Research Collaborations. 42 Staff & Students . 51 Division of Immunology and Genetics. .52 Division of Molecular Bioscience. .55 Division of Neuroscience. 57 High Blood Pressure Research Unit. .58 Students. .59 School Administration and Services . 61 Publications, Presentations & Patents. .63 Publications. 64 Patents . 71 Presentations. .72 Student Presentations. 76 Contact with our Community. .79 Commitment to Serving Our Community. 83 Support. 91 Grants. .92 Statistics. .97 Donors. .98 2 The John Curtin School of Medical Research Annual Review 2008 Selected Highlights 2008 JCSMR Health through Discovery How nerve impulses are generated in the brain Neuronal Signalling Group Research Fellow Dr Maarten Kole, along with Professor Greg Stuart and other members of the Neuronal Integration Laboratory, Neuroscience Program, have been working to increase our understanding of the way in which the nerve impulse, or action potential, is generated in nerve cells of the brain. Action potentials are the primary electrical signals used for fast communication between nerve cells. From previous research, it is known that action potentials are generated in a region of the nerve cell axon (the main output pathway of neurons) called the axon initial segment. In two separate papers published in the prestigious journal Nature Neuroscience, Kole, Stuart and colleagues have described the cellular and molecular mechanisms leading to action potential generation, showing that it is the result of a high density of voltage-activated sodium channels in the axon initial segment, which are tightly bound to the actin cytoskeleton. These sodium channels open as a result of a changed voltage across the cell membrane, allowing positively charged sodium ions to flow inwards, resulting in the generation of a single site with low action potential threshold and subsequently the triggering of the action potential. Collectively, these studies describe for the first time the fundamental cellular mechanisms used by neurons to generate electrical impulses, enabling complex neural processing of the brain. Kole, M.H.P., Ilschner, S.U., Kampa, BM, Williams, S.R., Ruben, PC and Stuart, G.J. (2008) Action potential generation requires a high sodium channel density in the axon initial segment. Nature Neuroscience 11(2): 178-186 Kole, M.H.P. and Stuart, G.J. (2008) Is action potential threshold lowest in the axon? Nature Neuroscience 11(11):1253-1255 Overturning the one cell — one antibody dogma Cancer and Vascular Biology Group Postdoctoral fellow Ben Quah, along with Professor Chris Parish and collaborators in the Divisions of Immunology and Molecular Bioscience JCSMR published the groundbreaking discovery that B lymphocytes - the immune cells responsible for making antibodies - share these antibodies with one another. Current concepts of immunity are based firmly upon Nobel-prize winning Australian immunologist Mac Burnet’s concept of ‘clonal selection’. In that view, each immune cell is restricted to making a single, unique antibody, so that production of a particular antibody can only be built up after a single cell has replicated into clonal copies many times. While the genes encoding antibodies are indeed subject to Burnet’s laws of one cell- one antibody, Quah, Parish and their colleagues discovered that the antibody proteins themselves are efficiently passed among different cells so that one cell can borrow a useful antibody made by another. This remarkable violation of the clonal selection dogma may help the immune system respond more rapidly to an infection, and points to a new process in cell biology that may have ramifications well beyond the immune system. Quah, B.J.C., Barlow, V.P., McPhun, V., Matthaei, K.I., Hulett, M.D. and Parish, C.R. (2008) Bystander B cells rapidly acquire antigen receptors from activatedB cells by membrane transfer. Proceedings of the National Academy of Sciences of the United States of America 105(11):4259-4264 The John Curtin School of Medical Research Annual Review 2008 3 Selected Highlights 2008 Discovering mechanisms of memory in the immune system: parallels with mechanisms of memory in the brain Immunogenomics Group PhD student Zuopeng Wu published the discovery of a new gene and mechanism essential for the immune system to produce the class of T cells that ‘remember’ an infection or immunization and resist re-infection His paper – co-authored with JCSMR supervisors Gerard Hoyne and Chris Goodnow and collaborators in Gottfried Otting’s group in the ANU Research School of Chemistry and at the Institute for Systems Biology in Seattle — featured on the cover of the prestigious journal Immunity. It revealed that a previously obscure protein, hnRNPLL, dramatically changes the splicing of messenger RNA molecules in memory T cells — changing the characteristics and longevity of the T cells much as a film editor can alter the plot of a film by splicing different scenes in and out. Remarkably, both the general strategy of altered splicing and the specific ‘scenes’ affected in memory T cells overlaps with emerging findings about RNA splicing changes occurring during the formation of memory in the brain. Thus, the study not only reveals a specific mechanism for memory in the immune system, but also a general strategy used in immune cells and brain cells. Wu, Z., Jia, X., de la Cruz, L., Su, X., Marzolf, B., Troisch, P., Zak, D., Hamilton, A., Whittle, B., Yu, D., Sheahan, D., Bertram, E., Aderem, A., Otting, G., Goodnow, C.C. and Hoyne, G.F. (2008) Memory T cell RNA rearrangement programmed by heterogeneous nuclear ribonucleoprotein hnRNPLL. Immunity 29(6):863-875 The role of calsequestrin in skeletal muscle contraction Muscle Research Group Dr Nikki Beard, Postdoctoral Fellow in the Muscle Research Group headed by Professor Angela Dulhunty, has worked with colleagues including other members of the Group and Magdolna Varsányi from Ruhr-Universität, Bochum, Germany to understand the mechanisms by which the skeletal muscle calcium binding protein calsequestrin plays a role in controlling muscle contraction. Published in the journal Cell Calcium, this research shows for the first time that phosphorylation of calsequestrin enhances its capacity to bind calcium. Appropriate binding of calcium is essential to the proper functioning of skeletal muscle in the regulation of movement. Additionally, this research identified an accessory protein, junctin, as being essential in mediating regulation of muscle contraction by calsequestrin. Beard, N.A., Wei, L., Cheung, S.N., Kimura, T., Varsanyi, M. and Dulhunty, A.F. (2008) Phosphorylation of skeletal muscle calsequestrin enhances its Ca2+ binding capacity and promotes its association with junctin. Cell Calcium 44(4):363-373 4 The John Curtin School of Medical Research Annual Review 2008 The goals of JCSMR are to • conduct research of the highest international standard into fundamental life processes and the pathologies of these processes which cause human disease • play a leadership role in medical research in Australia • provide outstanding training in medical research for young scientists and health professionals • apply new knowledge for better health outcomes. Selected Highlights 2008 Science Minister’s Prize for Life Scientist of the Year • Dr Carola Garcia de Vinuesa was awarded the Science Minister’s Prize for
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