The john curtin school of medical research Annual review 2012

ANU College of Medicine, Biology & Environment contents

Annual Review 2012 From the Director 3 The John Curtin School of Medical Organisation Chart 4 Research Committees 5

Community 7 Official Opening of Stage 3 8 Launch of The John Curtin Medical Research Foundation 9 Professor Gordon Ada 10 Open Day 11 Community Activities 12

Research in Review 2012 15 Eccles Institute of Neuroscience 16 Department of Genome Biology 29 Department of 36 Department of Pathogens and Immunity 45 Department of Molecular Bioscience 47 Department of Translational Medicine 56 Australian Phenomics Facility 60 Biomolecular Resource Facility/Genome Discovery Unit 61

Staff and student Achievements 63

Visitors and Collaborations 69

Staff and students 85 Department of Genome Biology 86 Department of Immunology 87 Eccles Institute of Neuroscience 88 Department of Pathogens and Immunity 90 Department of Molecular Bioscience 90 Department of Translational Medicine 92 APF and Animal Services 92 School Services 94 School Administration 95 Students 96

Publications, Presentations and Community Outreach 99

Support 129 Grants 130 Financial Overview 134 Donors 135 Sponsors 136

Annual Review 2012 1 2 The John Curtin School of Medical Research From the director

Zinkernagel. He will be sadly missed by his many friends and colleagues at the School, who have established the annual Gordon Ada New Investigator Award in his memory. In 2012, we finally completed the long and very necessary redevelopment project that resulted in the new John Curtin School of Medical Research building on the ANU campus. All our staff and students are once again under one roof, carrying out their research in state of the art laboratories and facilities. The Department of Neuroscience expanded and became the Eccles Institute of Neuroscience and we welcomed neuroscientists from the ANU Medical School and Research School of Biology to the building. In August, the 10-year project was finally complete, with local MP Dr Andrew Leigh (Member for Fraser) joining ANU Vice Chancellor Professor Ian Young to declare the third and final stage open in front of current and former staff and students, and supporters of the School. It is my very great pleasure to present the Annual Review from The John Curtin School of Medical Research for In March, Mr Simon McKeon ( 2011) 2012. In this document, we outline the scientific research joined us to launch The John Curtin Medical Research projects underway within the school, and highlight the Foundation at JCSMR. The Foundation was established achievements and successes of our staff and students to raise the public profile of medical research at The throughout the year. In addition, we showcase some of Australian National University, and to source funding the events that we have been involved with at the School, to ensure the continued success of that research. The University and Community level. I hope you will enjoy Foundation Board, led by inaugural Chair Dr Cameron reading the report, and will visit the website jcsmr.anu.edu. Webber, is currently working to support our scientists as au for further details. they carry out studies with the aim of preventing or curing diseases including cancer, diabetes and malaria, and to There were many honours, prizes and awards increase health outcomes nationally and internationally. celebrated at the School in 2012. I would particularly More information about the Foundation and this important like to congratulate Professor Chris Goodnow, who work can be found here: jcmrf.anu.edu.au was awarded The GlaxoSmithKline Award for Research Excellence in September for his pioneering work on In April this year we gathered to farewell JCSMR Director autoimmune, diseases and Professor Greg Stuart, Professor Julio Licinio, as he took up his new position who was elected Fellow of the Australian Academy of as Deputy Director for Translational Medicine and Head, Science for “seminal contributions to understanding how Mind and Brain Theme at the South Australian Health and information is processed by individual nerve cells within Medical Research Institute. As Director from 2009 – 2013, the brain”. Professor Stuart also received a Thomson Julio introduced the discipline of Translational Medicine Reuters Citation Award for the highest cited to the School, and his legacy includes the establishment Neuroscientist in Australia based on research volume and and early success of The John Curtin Medical Research impact over the ten-year period from 2002 to 2011. Foundation. We thank him for his leadership, and wish him well in his future endeavours. In September, we were very saddened to learn of the death of Emeritus Professor Gordon Leslie Ada. Professor Ada was Head of the Department of Microbiology at the Professor Christopher Parish School from 1966-1988, during which time he created and fostered a research environment that led to many Director, The John Curtin School of Medical Research significant immunological discoveries, including the work October 2013 that led to the award of the Nobel Prize in Physiology or Medicine to Professors Peter Doherty and Rolf

Annual Review 2012 3 Organisation Chart

AnU college of Medicine, Biology and environment

The John Curtin School of Medical Research 2012

director Professor Julio Licinio deputy director Professor Phil Board

departments

Genome Immunology Neuroscience Pathogens Translational Translational Biology & Immunity Biosciences Medicine (until September) Molecular Bioscience (from September)

Professor Professor Professor Professor Professor Professor David chris Greg carola Phil Board Julio tremethick Goodnow stuart Vinuesa (until september) Licinio Professor Angela Dulhunty (from september)

administration

School Manager Outreach and Education Director’s Offi ce Communications

Mr Gerry Lillicrap Dr Madeleine nicol Dr Anna cowan Ms Laura Vitler (from February)

services and support

ACRF Australian Operations Microscopy & Technical Safety & Biomolecular Phenomics Cytometry Services Training Resource Facility Resource Facility Facility

Ms stephanie Dr steve Mr Denis Ms cathy Mr Denis Ms Kate McKenzie Palmer Winslade coombes Gillespie coombes (until August) Ms sonya Glasson (from August)

4 The John Curtin School of Medical Research Committees

Executive Committee Dr Charani Ranasinghe Ms Michelle Townsend Professor Philip Board Mr Dennis Vukoja Dr Anna Cowan Ms Esmee Weil Professor Chris Goodnow Ms Anneloes de Graeff (by invitation) (until May) Safety Committee Dr Rebecca Haddock (until May) Professor Julio Licinio (Chair) Professor Philip Board (Chair) (from August) Mr Gerry Lillicrap (from February) Dr Geeta Chaudhri (Chair) (until August) Dr Madeleine Nicol (until May) Mr Mick Devoy Professor Chris Parish (Co-Chair from July) Dr Renae Domaschenz Professor Greg Stuart Dr Julia Ellyard Professor Carola Vinuesa Dr Sonya Glasson (from August) Mr Danushka Wijesundara (until May) Ms Diane Gooding Mr Gerry Lillicrap (from February) External Relations Committee Ms Kate McKenzie (until July) Dr Peter Milburn Professor Philip Board (Chair) Ms Suzy Pace Dr Anna Cowan Ms Jackie Stenhouse Dr Anselm Enders Dr Krisztina Valter (from September) Ms Anneloes de Graeff Professor Julio Licinio Animal Users Committee Mr Gerry Lillicrap (from February) Dr Madeleine Nicol (Convened December 2012) Professor Chris Parish Dr Anneke Blackburn Professor Thomas Preiss Professor Philip Board Professor Ian Ramshaw Ms Katrina Bowditch (ex officio) Ms Megan Clydesdale (ex officio) Group Leaders Forum Dr Lucy Coupland Professor Angela Dulhunty Professor Ian Ramshaw (Chair) Dr Suzanne Fowler (ex officio) All Group Leaders and Laboratory Leaders belong to the Group Leaders Forum, which meets monthly to discuss matters of importance relating Associate Professor Guna Karupiah to JCSMR Associate Professor Brett Lidbury Professor Klaus Matthaei Education Committee Dr Riccardo Natoli Dr Ian Parish Associate Professor John Bekkers Dr Charani Ranasinghe Dr Anneke Blackburn Dr Charmaine Simeonovic Dr Anna Cowan (Chair) Associate Professor Christian Stricker (Chair) Professor Simon Easteal Miss Preethi Eldi New Revenue Streams Committee Professor Chris Parish Mr Roy Ramiscal Dr Vicki Athanasopoulos Professor Ma-Li Wong Dr Ed Bertram Professor Philip Board Operations Committee Ms Anneloes de Graeff Professor Angela Dulhunty Mr Denis Coombes Professor Simon Easteal Professor Angela Dulhunty (Chair) Dr Julia Ellyard Dr Suzanne Fowler Professor Julio Licinio Ms Cathy Gillespie Mr Gerard Lillicrap Ms Sonya Glasson (from August) Professor Ted Maddess Professor Caryl Hill Dr Madeleine Nicol Dr Gavin Huttley Professor Chris Parish Mr Gerry Lillicrap Mr Geoff Sjollema Ms Kate McKenzie (until July) Professor Greg Stuart Ms Stephanie Palmer Dr Steve Winslade (Chair)

Annual Review 2012 5 6 The John Curtin School of Medical Research Community

Official Opening of Stage 3 Launch of The John Curtin Medical Research Foundation Professor Gordon Ada Open Day Community Activities

Annual Review 2012 7 Official Opening – Stage Three

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On 13 August 2012, Dr Andrew Leigh, Federal Member for Acting Director Professor Chris Parish agreed: “This is a very Fraser declared open the third and final stage of the new JCSMR exciting time for our research school. We are now well equipped building. Dr Leigh paid tribute to all those who had worked so to answer fundamental questions about disease development hard towards the redevelopment project, and wished current and and to use this knowledge to tackle some of the world’s major future JCSMR scientists research success in the new state of the health problems. JCSMR is home to some of the best minds in art laboratories and facilities. Australian biomedical research and the new facilities will enable ANU Vice-Chancellor Professor Ian Young said: “The new building us to continue our world-class research and also to attract more will house state-of-the-art clinical research suites and laboratory of the country’s best to work at ANU.” 1. Professor Chris Parish, Acting Director JCSMR space designated for clinical and biomedical research into fields 2. Dr Andrew Leigh MP, Federal Member for Fraser including genomics, translational and personalised medicine, 3. Dr Andrew Leigh MP and ANU Vice-Chancellor Professor Ian Young unveil the dedication stone 4. Professor Ian Young, Dr Andrew Leigh MP and Professor Chris Parish pharmaco-genetics and vision, and neurological and sensory 5. Dr Peter Jeffrey, Dr Barbara Treacy, Dr Rose Mason and Professor Peter Treacy diseases including memory loss, epilepsy and blindness”. 6. Mr Robert Tupper, Mrs Valerie Tupper and Mrs Eva Henry

8 The John Curtin School of Medical Research Launch of The John Curtin Medical Research Foundation

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Launched in March 2012, The John Curtin Medical Research Foundation was established to raise the public profile of medical research at The Australian National University, and to source funding to ensure the continued success of that research. 1. Inaugural Foundation Chair, Dr Cameron Webber OAM 2. Dr Grace Moshi and guest with His Excellency Mr Rubem Corrêa Barbosa, The Ambassador from Brazil 3. Dr Lucy Coupland, Mrs Bhama Parish, Mrs Anne Coupland and Professor Chris Parish 4. Mr Simon McKeon, Australian of the Year 2011, launches The John Curtin Medical Research Foundation 5. Emeritus Professor David Curtis, Professor Judith Whitworth and Professor Stephen Redman 6. JCSMR Director Professor Julio Licinio, ANU Vice-Chancellor Professor Ian Young, and Chair of the JCMRF Board, Dr Cameron Webber

Annual Review 2012 9 Gordon Leslie Ada AO, FAA

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6 December 1922 – 25 September 2012 1. Professor Ada at his desk at JCSMR in 2003 2. Professor Ada and his family at the ceremony to name the Gordon Ada Videoconferencing room, JCSMR, Professor Gordon Ada one of Australia’s leading microbiologists, 2007 3. (l-r) Nobel Laureate Professor Peter Doherty, Emeritus Professor Robert Blanden, Nobel Laureate Professor passed away peacefully in after a short illness. He was Rolf Zinkernagel and Emeritus Professor Gordon Ada at The Fenner Conference 2007 4. aged 89. Professor Ada made many contributions to the field of Professor (l) and Professor Gordon Ada – December, The ANU Calendar 2005 virology and immunology as well as to JCSMR, the Australian Academy of Science, and the World Health Organisation. Professor Ada will be sadly missed by his friends and colleagues at JCSMR, who will establish an Annual Award and Oration in his memory.

10 The John Curtin School of Medical Research Open Day 2012

On Open Day, we invite everyone with an interest in our work to visit the School. Take a tour of our laboratories, speak with our scientists, and learn more about our important work as we try to find causes and cures for diseases including cancer, diabetes, high blood pressure, infectious and autoimmune diseases, malaria, metabolic disorders and obesity. For information about our next Open Day, please visit jcsmr.anu.edu.au

Annual Review 2012 11 COMMUNITY ACTIVITIES

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1. Acton Walkways Tours visiting internal and external spaces around the new JCSMR building as part of their experience of the ANU campus 2. Peter and Dorothy Barcleay with Marilyn Fenner at the JCSMR Director’s Christmas morning tea, December 2012 3. Professor Narci Teoh, Sir David Akers-Jones and Dr Cameron Webber at the JCSMR Director’s Christmas morning tea, December 2012 4. Professor Ted Maddess showing Mr Charles Bootes and Mrs Gretel Bootes the Fundus Camera in the Clinical Research Suites at JCSMR, purchased with the support of the Bootes Foundation

12 The John Curtin School of Medical Research 5 6

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5. One of four groups of National Youth Science Forum students visiting JCSMR to speak with scientists in their laboratories. These students are selected for their interest in Science, Engineering and Technology, and are supported by local Rotary clubs to visit Canberra for two weeks in January 6. Professor Chris Parish, Dr Grace Moshi and Dr Lucy Coupland celebrate the beginning of a research project into sarcoma, to be funded with assistance form the Sarah-Grace Sarcoma Foundation. Dr Moshi and many devoted volunteers have raised these funds through various functions and activities including a soiree at the Finnish Embassy, a movie night at JCSMR and the sale of ‘Kick-Sarcoma’ green shoelaces 7. A delegation from the Indian National Academy of Sciences visited JCSMR on 5 December, 2012. The delegation was led by Professor Krishan Lal, pictured on the left. 8. Professor Thomas Preiss leader of the RNA Biology Group, Department of Genome Biology, JCSMR, ANU gave the fourth lecture on 27 August as part of the JCSMR Director's 'Health through Discovery' Public Lecture Series

Annual Review 2012 13 14 The John Curtin School of Medical Research Research in Review 2012

Eccles Institute of Neuroscience Department of Genome Biology Department of Immunology Department of Molecular Bioscience Department of Pathogens and Immunity Department of Translational Medicine The Australian Phenomics Facility ACRF Biomolecular Resource Facility and Genome Discovery Unit

Annual Review 2012 15 Eccles Institute of Neuroscience

Head

Professor Greg Stuart

Group Leader Blood Vessel Group Professor Caryl Hill Neuroimmunology & Cardiovascular Dysfunction Laboratory Dr Rebecca Haddock Cerebral Cortex Group Associate Professor John Bekkers Diagnostics for Eye Diseases Group Professor Ted Maddess Neuronal Network Group Associate Professor Christian Stricker Neurophotonics Laboratory Dr Vincent Daria Neuronal Signalling Group Professor Greg Stuart Brain Development Laboratory Dr Zan-Min Song Retinal Cell Damage and Repair Group Dr Krisztina Valter-Kocsi Retinal Development and Aging Group Professor Jan Provis Neural Control Systems Laboratory Dr Jason Potas Synapse and Hearing Group Professor Bruce Walmsley Visual Neuroscience Group Professor Trevor Lamb

16 The John Curtin School of Medical Research New Treatments for High Blood Pressure

ion channel in the cell membrane which aetiology and unwanted side effects Eccles Institute was not previously considered to play of many therapies on the metabolic this role. Since current therapeutic abnormalities associated with obesity. Our of Neuroscience strategies do not affect this channel, we studies of peripheral vascular function in propose that it plays an important role diet-induced obesity have demonstrated in the development of therapy resistant that hyperactivity of the sympathetic Blood Vessel Group hypertension. Our studies are determining nervous system during obesity is the mechanism by which this change accompanied by expansion of the Professor Caryl E Hill in ion channels occurs and testing the sympathetic perivascular innervation. We effects on hypertension of targeting this now have exciting new data that these Neuroimmunology and channel. changes result from a complex interplay Cardiovascular Dysfunction A key role for cell coupling through gap with the immune system. Laboratory junctions and their connexin (Cx) proteins Taken together, our studies are providing is now emerging as an important facet new insights into the mechanisms Dr Rebecca E Haddock in the development of cardiovascular by which the peripheral vasculature disease. Deletion of Cx40 in mice can contribute to the development of Hypertension is the major risk factor for produces profound hypertension, vascular dysfunction and hypertension. cardiovascular disease, which itself is however Cx40 is expressed in the These studies provide support for the the leading cause of premature death heart, kidney and blood vessels, so the proposal that cardiovascular events worldwide. The current obesity epidemic precise contribution of these elements is result from changes in microvascular is also characterised by hypertension unknown. As Cx40 is a major contributor function and that targeting these changes and increased cardiovascular risk, with to coupling of endothelial cells of will reveal novel therapeutic strategies hyperactivity of the sympathetic nervous resistance arteries, we have developed for the treatment of therapy resistant system an important contributing factor. transgenic mice with a mutation in Cx40 hypertension. However, some 30% of hypertensive selectively in the vascular endothelium. patients exhibit a therapy resistant form jcsmr.anu.edu.au/research/eccles- Our studies have shown that changes which does not respond to current clinical institute-neuroscience/blood-vessel in cell coupling in the endothelium can treatments. have a profound effect on the way arteries jcsmr.anu.edu.au/research/ The smallest arteries and arterioles respond to changes in blood pressure eccles-institute-neuroscience/ provide the greatest resistance to blood and and that this leads to arterial stiffness, neuroimmunology-cardiovascular- flow and enhanced constriction of these a characteristic of both ageing and dysfunction vessels contributes to hypertension. We cardiovascular disease. have shown that, during cardiovascular Hypertension as a consequence of disease, there are changes to the way diet-induced obesity is a major clinical that blood vessels constrict. Thus calcium problem with progress towards effective influx, which is essential for vascular treatments hampered by complex constriction, now occurs through an

Annual Review 2012 17 Odours, brain circuits and epilepsy

primary olfactory cortex of mice, place Eccles Institute the slices in a recording chamber, then study the electrical signalling between of Neuroscience individual neurons (nerve cells). In the past year we have used this approach to study the properties of neurons in the olfactory Cerebral Cortex Group cortex that we think might contribute to its propensity for epileptic seizures. Associate Professor John We have also set up a new technique, Bekkers called optogenetics, that allows us to My group studies a region of the brain selectively stimulate neurons using flashes called the primary olfactory cortex, of blue light. Figure 1 shows an example which is important for recognising and of a brain slice used in one of these remembering odours. Every time you sniff experiments. The green spots in layer 2a a rose or a cup of coffee, your primary are individual neurons. Note that some of olfactory cortex swings into action, the neurons appear yellowish; these are building up a mental image of “coffee” the ones that can be stimulated by light. or “rose” from the chemicals you inhale. During the past year we have also By studying the olfactory cortex we hope conducted many in vivo experiments. to understand how the brain processes For these, we anaesthetise a mouse, sensory data in order to assemble a apply puffs of odorants to its nose, then coherent picture of the outside world. measure the responses of neurons within We are also interested in the olfactory its primary olfactory cortex. In one series cortex because of the insights it provides of in vivo experiments we used a laser into brain diseases. The sense of smell is microscope to record from known types unusually sensitive to a number of brain of neurons while applying odorants. disorders, but the one of most interest Figure 2 shows the appearance of one to us is epilepsy. Recent clinical research of these neurons (red) in the microscope. has shown that epileptic seizures are We found that these neurons respond in often amplified within the olfactory cortex, unique ways to odorants. allowing them to spread. We are trying In summary, we have made good to understand why this is so, thereby progress in uncovering the secrets of this clarifying the causes of epilepsy. fascinating brain region, shedding light on We perform two broad kinds of the complex computations performed by experiments in the laboratory, in vitro and the brain when we sniff an odour. in vivo. For in vitro experiments we cut jcsmr.anu.edu.au/research/eccles- thin slices of living brain tissue from the institute-neuroscience/cerebral-cortex

18 The John Curtin School of Medical Research Advanced multifocal analysis of the visual system, with applications to blinding diseases

There has been some debate over column) simply results in the cortical Eccles Institute the years on whether it is better to representation shifting left or right on the test for AMD in dark- or light-adapted sheet without changing its dimensions of Neuroscience conditions. The debate arose because the (right column), leading to similar sized photoreceptor cells of our eye that help responses being measured on the scalp. us see in dim conditions, the rod cells, In practice, rings of stimuli can be divided Diagnostics for Eye seem to die earlier in the development radially, like the segments of a dartboard, Diseases Group of AMD than the cells responsible for into smaller stimulus regions. From a daylight vision, the cone cells. That clinical standpoint it means that scaled Professor Ted Maddess being said cone cells are also known to versions of the test array can be used to This year saw several discoveries related be abnormal by the time the rods die. If probe central or peripheral vision with no to our prototype device for objective testing in the dark gave better results, loss of signal quality. visual field testing, the TrueField Analyzer health professionals would need special jcsmr.anu.edu.au/research/eccles- (TFA), a device that Associate Professor darkened rooms, and the tests would be institute-neuroscience/diagnostics-eye- Andrew James and I have been long if patients had to wait to adapt to the diseases developing with Seeing Machines. The dark. We found that TFA works equally TFA records tiny changes in the diameters well under bright or dim conditions. of the pupils of the eyes in response to A big advance for TFA is our newly visual stimuli and it then uses these to discovered clustered volley stimulus make maps of how well people can see method, which greatly improves the signal in each part of their visual field. Both eyes quality of the pupil responses, and this are tested at the same time. The resulting translates into improved diagnostic power visual field maps can be used to diagnose in both AMD and glaucoma. and monitor a range of eye and brain problems. Another noteworthy finding was that if one organises multifocal stimuli in a Originally the TFA was conceived as a certain type of dartboard pattern, then device for managing glaucoma, a major the electrical responses of the brain blinding disease. New experiments found measured on the scalp do not get smaller that the TFA does a surprisingly good as subjects view the stimuli from further job of measuring early stage damage to and further away. The accompanying the eyes caused by age-related macular figure shows stimulus arrays as viewed degeneration (AMD) and diabetes, the from three different distances (A, C, and two leading causes of blindness in E, left column), and the representation Australia and the western world. of those stimuli on the (flattened) cortical sheet is shown in B, D, and F (right column). Scaling the stimuli (left

Annual Review 2012 19 Communication between nerve cells

transmitter release at high stimulus rates with an integrator, which relays Eccles Institute and are therefore well suited to relay information about constancy. In addition, constant information. Type 1 synapses, the unmatched cases still showed of Neuroscience however, due to their rapid depression, properties consistent with integrators, are suited to changes in stimulation as each though with distinct features. Neural Network Group they respond vigorously at the onset of a Using brain slices we investigated change. if the postsynaptic firing property Associate Professor Christian It has been known that postsynaptic could be changed dynamically. Using Stricker firing is either constant (class 1) noradrenaline, cells that showed firing or shows spike-adaptation during adaptation were converted into regular Release of neurotransmitter packaged which the firing rate drops (class 2). firing ones. Conversely, regular firing in vesicles is the means by which We wondered whether the different could be converted into firing adaptation nerve cells communicate with each types of synapses and the firing of if calcium stores were blocked. other. Within a network of neurons, the postsynaptic cells are matched the communication is only effective These results suggest that the operating for efficient coding. The idea is that a if the response to release of the mode of a network is determined by synaptic input that maintains activity neurotransmitter is strong enough both synaptic and firing properties. at a high rate but is received by a cell to generate an action potential. Studying these factors simultaneously with frequency adaptation is unlikely to Consequently, in this process, there is necessary for understanding neuronal transfer a constant input rate. However, are two main players: the synapses coding. if the synapses that depressed quickly where the vesicles of neurotransmitter transmitted information to postsynaptic jcsmr.anu.edu.au/research/eccles- are released and the properties of cells with firing adaption (matched case), institute-neuroscience/neuronal-network the postsynaptic cells receiving the efficient encoding of a rate change could information. occur. Our previous work showed that Exploring different configurations in synapses show different forms of simulations between synapse type dynamics during firing: one set of and firing class, we characterised the synapses depresses as a lot of vesicles resulting input-output transformations. are “used up” and these recover back As predicted, when type 1 synapses to their normal state at a constant rate were connecting to class 2 firing (type 1). The other set of synapses, cells, the output was consistent with though, depresses independently of that of a coincident detector; i.e. this vesicle release and the recovery from configuration can relay rate change this depression is much accelerated information. When, however, type 2 at high stimulus frequencies (type 2). synapses were connected to class 1 We have previously shown that type 2 firing cells, the output was consistent synapses are capable of maintaining

20 The John Curtin School of Medical Research Optical Techniques to Analyse the Brain

How a neuron processes all these input neuronal signals have clear advantages Eccles Institute signals, ultimately leading to an output over conventional electrical stimulation (or action potential), is an important using micropipettes. This will significantly of Neuroscience problem in neuroscience that is not yet speed up the study of neuronal circuits, fully understood. Such venture could which brings us closer to understanding Neurophotonics Laboratory provide us with a better understanding of how the brain works. how these neurons process information jcsmr.anu.edu.au/research/eccles- thereby extending our capacity to Dr Vincent Daria institute-neuroscience/neurophotonics understand neuronal dysfunction, e.g. The neurophotonics group is involved in neuropsychiatric and neurodegenerative a multi-disciplinary collaborative venture diseases. The dynamic properties of using between physicists and neuroscientists light induced generation and recording of to make use of novel optical techniques to analyse the brain. In this collaboration, we develop a two-photon microscope, which incorporates a 3D holographic laser projector. The microscope allows us to render the 3D morphology of a neuron while the holographic projector produces multiple laser foci projected along the neuron’s dendritic tree. Each focus functions as a probe capable of manipulating and recording neuronal activity. To manipulate neuronal activity, we introduce chemically caged neurotransmitters, which can be uncaged by light. Using the holographic laser projector, we can dynamically configure the light pattern to uncage the neurotransmitter and locally stimulate synapses at multiple sites along the dendritic tree of a neuron. This process emulates the many synapses neurons receive from neighbouring neurons. In addition, using calcium sensitive and voltage-sensitive dyes, we can use each focus to monitor changes in fluorescence, enabling optical recording of neuronal activity.

Annual Review 2012 21 Understanding the brain neuron by neuron

dendritic excitability of these cells. This localised within spines. This research Eccles Institute research has relevance to diseases of increases our understanding of spine the nervous system where excitation and function and may have relevance to of Neuroscience inhibition become unbalanced, as can diseases associated with loss of memory occur in epilepsy and schizophrenia. such as Alzheimer’s disease.

Neuronal Signalling Group Coding of binocular visual jcsmr.anu.edu.au/research/eccles- information institute-neuroscience/neuronal- signalling Professor Greg Stuart Visual information received by our eyes The Neuronal Signalling Laboratory is combined in the brain to form a single within the Eccles Institute conducts basic view of the outside world. In order to research on how nerve cells in the brain generate a single coherent map of process information. This work involves visual space, input from the two eyes is recording activity from single nerve cells combined in the brain. This convergence (technically called neurons) using both occurs at the level of the cortex. How the electrical and optical techniques. Over the cortex integrates visual information from past year we have been investigating the the two eyes is unclear. In this project following issues: we have been investigating how single neurons in primary visual cortex process Regulation of excitability by inhibition information from the two eyes. This There are two main types of neurons research has relevance to diseases of the in the brain: those that increase nerve visual system as occurs in various forms impulse generation (excitatory cells) of blindness. and those that reduce nerve impulse generation (inhibitory cells). These Calcium signalling in dendritic spines different cell types work in balance to Input onto many neurons in the brain regulate brain activity. The main chemical occurs onto specialized projections on transmitter used by inhibitory neurons is dendrites called dendritic spines. Calcium the amino acid gamma aminobutyric acid signaling in dendritic spines is known or GABA for short. In this project we have to be critical of induction of synaptic investigated the function of different types plasticity, which is thought to underlie of GABA receptors (type A and type B) memory formation in the brain. We have in the regulation of neuronal excitability recently been investigating calcium in cortical pyramidal neurons. We find signaling in dendritic spines during action that GABA acts via different receptors potentials, and find that this is regulated and mechanisms to regulate somatic and by calcium-activated potassium channels

22 The John Curtin School of Medical Research Stem cell transplantation in treating cerebellar cell loss in Hirschsprung’s disease

of rats with Hirschsprung’s disease. Eccles Institute Our pilot study with unlabelled stem cells from cultured cerebellum showed of Neuroscience that the recipient rats survived the operation and lived to adulthood. We also successfully developed a surgical Brain Development procedure (colostomy) to make the Laboratory gut to open directly on the abdominal wall, which allows the recipient rats Dr Zan-Min Song to survive into adulthood and to give About 1/5000 infants are born with the time for transplanted stem cells to blocked gut due to the lack of nerve develop into functional nerve cells. We cells in the gut wall, a condition will analyse the growth and connections known as Hirschsprung’s disease. made by transplanted cells in the Although surgical removal of affected recipient cerebellum using specific gut is a life saving procedure, many labelling techniques, and analyse the patients are left with other neurological restoration of cerebellar functions after disorders, including congenital central stem cell transplantation. The results will hypoventilation, neural deafness, provide important information on how seizures and mental retardation. Our the stem cell technique be used for the study in a rat model of Hirschsprung’s treatment of brain anomalies in human disease showed a marked deficit in Hirschsprung’s disease. nerve cell numbers in part of the brain jcsmr.anu.edu.au/research/eccles- called the cerebellum. We hypothesise institute-neuroscience/neuronal- that stem cell transplantation therapy is signalling/brain-development a viable strategy for treating the brain cell loss and restoring brain functions by transplanting neural stem cells from normal rat brain into the cerebellum of a rat model of Hirschsprung’s disease. We have been able to isolate stem cells from the cerebellum of normal neonatal rats and grow them into a ball of cells called neurosphere in culture. We will genetically label the cells with a green protein and then the labelled cells will be transplanted into the cerebellum

Annual Review 2012 23 Degenerative diseases of the retina

is the activation of an immune response, protect the remaining neurons. However, Eccles Institute and it is responsible for the progression of when the neuronal cell loss becomes the disease. Controlling this inflammation excessive, Müller cells try to heal the of Neuroscience is a one possible way to prevent the retina by proliferating to fill the created degeneration or slow the progression of space. The scar tissue created by these Retinal Cell Damage and the disease. reactive Müller cells can reduce retinal We are testing two possible therapeutical function and can impede on the success Repair Group approaches to target this inflammatory of any further treatment. activation. (1) We have shown that In collaboration with Dr Michele Madigan Dr Krisztina Valter-Kocsi irradiation with 670nm light significantly from UNSW, Dr Sunita Biswas-Legrand, This group is testing cell biology- reduces the loss of vision cells in this a medical student was examining the based, non-invasive therapies that may model. Treatment with this wavelength effects of 670nm light on Müller cell prevent or reduce the severity of retinal reduces the presence of inflammatory cultures. We have found, that irradiation degenerative diseases. cells recruited to the retina and prevents with 670nm light reduces the proliferation One such degeneration is Age-related them entering the tissue. More recently, of the cells. Jack Williams Honours Macular Degeneration, the leading cause were able to show the same protective student was conducting experiments of blindness in the Western world, among power of this light in a mouse model also. to test the effects of 670nm light on people over the age of 60. This disease (2) Another possible treatment can the Müller cells in the live retina. His affects the central area of the retina target a specific element of the preliminary results confirmed our findings that is responsible for colour vision, the immune response, the activation of the in the cell culture. formation of a sharp image and enable us complement system. We are testing the jcsmr.anu.edu.au/research/eccles- to perform fine work. The more common effects of the Vaccinia Virus Complement institute-neuroscience/retinal-cell- form of the disease is ‘dry AMD’. In Control Protein (VCP) in our model. damage-and-repair this form of the disease, vision cells are Nilisha Fernando, Honours student in gradually lost, specifically in the centre of my laboratory was examining retinas the retina, causing a disruption in central treated with this drug and was able to vision. The loss of cells is relentless, and demonstrate that it effectively reduced in the absence of effective treatment, complement activation in treated retinas. leads to blindness. We have started investigating the effects We have characterised a rat model that of 670nm light on one of the major mimics dry AMD. In collaboration with supportive cells of the retina, the Müller Professor Jan Provis, using this model cells. These cells are important for the we have been able to identify processes well being of the retina, though when the leading to the loss of the vision cells and retina is injured, they react by recruiting the progression of the disease. One of immune cells to clear off dead cells, up- the key events in the degenerating retina regulating neuroprotective factors to try to

24 The John Curtin School of Medical Research Macular Degeneration

Macrophages are one of the immune tomography (OCT) to get a better Eccles Institute cell types that play a pivotal role in understanding of the condition macula retinal degeneration in these models hole in which there is a perforation of of Neuroscience and in AMD. Dr Matt Rutar has shown the retina in the centre of the fovea. PhD that if macrophage-recruiting signals student Zabrina Abdool is analysing OCT can be blocked, then macrophages are images of macula holes and evaluating Retinal Development and supressed and the retina is protected visual acuity before and after surgery, with Aging Group from degeneration. Dr Krisztina Valter and the ultimate aim of predicting surgical Riza Alberricin have shown that treatment outcomes. Professor Jan Provis with 670nm light reduces macrophage Most recently, hand-held OCT devices This team is interested in the macula recruitment and retinal damage in a have been developed that have enabled region of the human retina, how it mouse model, and Matt Rutar has clinical teams to track development of the develops and why it is vulnerable to observed similar effects using 670nm macula and the fovea in vivo in premature degeneration associated with age (age- light treatment in the rat model. Honours infants. We recently published a study related macular degeneration, AMD). student Mandy Ma found that the effects comparing for the first time traditional The macula is the part of the retina that of 670nm light treatment are dose- tissue section images of the developing observes the centre of the visual field, and dependent. The mechanism of action of fovea with images captured from 39 allows us to see fine details the red light, however, is not understood infants born prematurely. The infant and Dr Riccardo Natoli is leading AMD is reaching epidemic proportions, macula is distinctive because the outer experiments involving scientists at the costing around $5 billion to Australians layers of retina in the region surrounding Universities of , Adelaide each year in lost productivity, quality of the fovea develop at a faster rate than and , aimed at identifying its life, special assistance and aids, and in those within the fovea; the study shows mode of action. costly therapeutics for the neovascular, that this delay in maturation of the or ‘wet’ form of AMD. There are multiple In other experiments, Dr Natoli and PhD fovea is clear in OCT images. We also risk factors for the disease, however one student Kartik Saxena have examined observed significant individual variation of the most significant is a genetic variant the role of post-transcriptional regulation in the development of outer retina. The that points to dis-regulation of part of of gene expression in the rat model, study provides the groundwork needed the innate immune system. We are using identifying the same microRNAs in the to track and understand the involvement animal models to mimic features of one degenerating rat retina as have been of abnormal foveal maturation in preterm form of AMD – the so-called ‘dry’ form found associated with AMD. infants where visual outcomes are poor, which does not involve proliferation of Because the macula is so important to an and to analyze treatment outcomes in this blood vessels – to study the immune independent lifestyle, we also participate population. responses. There are no treatments for in a number of collaborative studies jcsmr.anu.edu.au/research/eccles- the dry form of AMD. We are trying to aimed at applying our understanding of institute-neuroscience/retinal- understand the mechanisms that trigger macula anatomy to ‘real life’ problems. Dr development-and-aging complement activity in the retina, the Rohan Essex of The Canberra Hospital is cells and the signals involved, and how to leading a study using optical coherence modify them in a cost-effective manner.

Annual Review 2012 25 Processing information in the brain

injury can improve behavioural and the anatomical location and sensory Eccles Institute electrophysiological outcomes, alter the quality of the source input. If successful, balance of inflammatory cell populations, we will be able to extract information of Neuroscience reduce cell death and increase from these signatures to tell us what part neural sprouting in the spinal cord. In of the body is experiencing sensory input collaboration with Engineering (ANU), we as well as the quality of that sensation. Neural Control Systems are developing novel nanofibre scaffolds While a tactile sensory prosthetic device Laboratory and hydrogels for use as nerve graft is currently futuristic, data obtained from bridges and artificial extracellular matrix. our basic research is proving useful for Dr Jason Potas We are engineering these materials to improving our understanding of sensory The central nervous system is a retain and release biological factors information processing. command centre that controls into the surrounding tissues at the site jcsmr.anu.edu.au/research/eccles- various aspects of our everyday lives of implantation at controlled levels and institute-neuroscience/neural-control- using autonomic and conscious intervals. We have recently conjugated systems control systems. We are interested interleukin-10 to nanofibre scaffolds in understanding how information is and have demonstrated its bioactivity coded, relayed and processed by the in vivo. This factor naturally inhibits the peripheral and central nervous systems, inflammatory process following neural and how this information is utilised and trauma. integrated. Also of interest are how Other projects in our laboratory these systems are affected by injury examine sensory pathways with the and disease, how they adapt or are long-term view of developing a sensory modified and the mechanisms involved. prosthesis. Our future goal is to one A better understanding of how the brain day decode sensory information from processes information will provide us below a spinal cord lesion and artificially with new strategies for tackling the relay this to higher brain centres challenges associated with neural injury where sensory perception could be and disease as well as provide us with experienced in the absence of intact new insight into designing novel artificial spinal pathways following injury. The control systems. figure below demonstrates a functional We are currently investigating the use map generated by recording responses of photobiomodulation and nanofibres at different locations (black circles) on to promote nervous tissue regeneration the surface of the brainstem that were of peripheral nerves and the spinal evoked by stimulation of two different cord. We have demonstrated that the nerves. We believe these electrical use of 670 nm light following contusion signatures can be decoded to predict

26 The John Curtin School of Medical Research Hearing, Deafness and Tinnitus

The cochlea is arranged so that different Eccles Institute regions systematically respond to different sound frequencies, in a so called of Neuroscience ‘tonotopic’ organisation. This tonotopic organisation is preserved in the brain, from the first auditory nucleus in the Synapse and Hearing Group brainstem all the way up to the auditory cortex. Professor Bruce Walmsley Sensory information is represented in The proper development and functioning the brain by patterns of nerve impulses of the auditory system requires auditory generated within populations of neurons. nerve activity. Our experiments have A key feature of this process is the shown that the properties of auditory ability of the sensory input to shape the neurons and synapses are very different properties of neurons and their synaptic in the brains of congenitally deaf mice. inputs, so that the network becomes Auditory neurons may be more excitable, tuned to efficiently interpret the sensory and the normal tonotopic gradients of signals. Our laboratory is investigating neuronal properties are disrupted in deaf these processes in the auditory system. mice. Our experiments have also shown that in normal hearing mice, exposure Sounds entering the ear are transformed to moderate sounds is sufficient to alter by the cochlea into trains or patterns of the expression of particular proteins nerve impulses, which are then relayed (such as potassium channels) in auditory to the brain via the auditory nerve. neurons. Understanding the role of neural The transformation from mechanical activity in modifying or regulating the vibrations to electrical nerve impulses properties of auditory neurons and their occurs at specialised synapses between synaptic connections is important to the sensory ‘hair cells’ and neurons in understanding how the brain interprets the cochlea giving rise to the auditory sounds, and the changes that occur in nerve. This synaptic connection is the auditory dysfunctions such as deafness most sensitive in the nervous system, and tinnitus. with many singly released quanta of neurotransmitter capable of generating a jcsmr.anu.edu.au/research/eccles- nerve impulse in the auditory nerve. One institute-neuroscience/synapse-and- of our current projects is investigating the hearing fundamental mechanisms underlying this exquisite transformation in the cochlea.

Annual Review 2012 27 Photoreceptors: Activation, recovery, and evolution

that following very intense and prolonged Eccles Institute exposures, that bleached virtually all of the photopigment, the cone recovery was of Neuroscience slower than that obtained following smaller bleaches. We interpreted this finding to indicate the likely depletion of the amount Visual Neuroscience Group of retinoid (i.e. vitamin A) stored in the retina and retinal pigment epithelium. Professor Trevor Lamb In collaboration with Dr Omar Mahroo In a separate study, I returned to ( and Cambridge, UK), I investigating the evolution of vertebrate investigated the time-course of photoreceptors. By analysing new the electrical responses of rod and results that have been reported by cone photoreceptors in the living other groups over the last several years, human eye, by measuring the ERG on a wide range of topics related to (electroretinogram). Our findings were photoreceptors (including the phylogeny published in two papers in Documenta of opsins, the embryonic development Ophthalmalogica. of the retina, and the molecular Recording the electroretinogram from a volunteer. signature in photoreceptors of primitive We wanted to know whether it was species) I have been able to update our possible to predict the time-course of the previously developed scenario for the rod photoreceptor response to onset of likely sequence of events underlying the steady light (i.e. to a ‘step’ stimulus of evolution of vertebrate photoreceptors, light) from knowledge of the response to retina, and eye. To continue this line of a brief flash of light, which is what is more research, I have re-built our single-cell conventionally measured. We discovered suction pipette electrophysiological that the responses to steps can indeed rig, following our move into the new be predicted by integration of the flash JCSMR building earlier in the year. This response, and we developed a simple will enable comparison of the electrical equation to characterise the onset phase responses of photoreceptors of ‘primitive’ of those responses. species (such as hagfish and lampreys) In a second study of human ERGs, this that should provide further clues to the time examining the responses of the evolution of our own rods and cones. cone photoreceptors, we determined jcsmr.anu.edu.au/research/eccles- the time course of recovery of the institute-neuroscience/visual- cells after the termination of intense neuroscience ‘bleaching’ illumination. We discovered

28 The John Curtin School of Medical Research Department of Genome Biology

Head of Department

Professor David Tremethick

Group Leader Alternatives to Animal Research through Associate Professor Brett Lidbury Bioinformatics Group Chromatin and Transcriptional Regulation Group Professor David Tremethick Computational and Conceptual Biology Group Professor Jill Gready Computational Genomics Group Associate Professor Gavin Huttley Genome Diversity and Health Group Professor Simon Easteal RNA Biology Group Professor Thomas Preiss

Annual Review 2012 29 Alternatives to animals in biomedical research

has expertise in advanced statistics and a non-fatigued control cohort, has been Department of in silico machine learning, as well as recruited for this study. From these human virology and molecular genetics. This cohorts pathology blood test results, Genome Biology style of investigation will also rely upon genetic, serum cytokine, gut microbiology biological validation in the laboratory, thus and participant clinical data were blending in silico methods with “wet lab” collected. This extensive data collection is Alternatives to Animal results and genetic data. under interrogation via machine learning Research through Via alternative and innovative methods, algorithms to identify data networks that Bioinformatics the group ultimately aims to improve detect potential ME-CFS biomarkers, fundamental knowledge on disease to assist diagnosis and monitoring, and Associate Professor Brett Lidbury processes post-infection, and enhance furthermore, enhance prediction of ME- CFS severity and outcome. The Alison AARB has been established to develop laboratory diagnoses of infection and Hunter Memorial Foundation (AHMF) alternative methods and strategies to associated disease. AARB’s research provides funding support. replace animals and animal products, does not use animals or animal products, while achieving medical advances and looks to develop animal alternatives In summary, AARB will advance through fundamental biomedical research. through a systems approach. fundamental biomedical science without As required by alternative research Of particular note to overcoming human reliance on animals, or products derived approaches, the nature of our research complexity, AARB uses sophisticated from animals. Specific aims include the is focused entirely on human biology machine learning techniques, for example deeper understanding of pathology and disease, with the inherent challenge support vector machines (SVM), on post-infection, and as an applied aspect of how to overcome the variation and human data. This algorithm allows the to such fundamental discovery, advance diversity of humans while pursuing modelling of spaces between points medical diagnostics and disease biomedical discovery. (kernels) in high dimensional space, prediction. In the longer term AARB will also contribute to the establishment Our primary biomedical research interests providing a powerful method for detecting of a unit to support and encourage are in infectious disease, particularly disease or infection associated patterns alternatives research the genetic basis of resistance or in complex data. In concert with SVMs, susceptibility to disease post-infection, recursive partitioning, or “tree” methods, jcsmr.anu.edu.au/research/genome- and the role of infection and immunity in are also used to untangle human data. biology/alternatives-animal-research- chronic fatigue syndrome (ME-CFS). The development of a possible animal through-bioinformatics As an alternative to animal models, which replacement alternative for the study are commonplace for infectious disease of ME-CFS is in its final stages, and and ME-CFS, the group relies primarily combines a human volunteer study on pattern recognition methods from the with the pattern recognition and field of knowledge discovery, applied to statistical methods described above. mass human data sources. To obtain the An experimental cohort that fulfils the desired research outcomes, the group Canadian Criteria for chronic fatigue, and

30 The John Curtin School of Medical Research The Epigenetic Code

have demonstrated that one of its spermatogenesis. We therefore propose Department of fundamental functions is to maintain the a novel model whereby H2A.Lap1 stability of chromosomes. Specifically, it coordinately regulates gene expression Genome Biology maintains the integrity of the centromere by directly opening the chromatin and surrounding heterochromatin where structure of the TSS at genes regulated it assembles compacted domains during spermatogenesis. We also detect Chromatin & Transcriptional using both active and inactive histone heterotypic H2A.Z/H2A nucleosomes at Regulation Group modifications. We have recently active promoters during spermatogenesis, discovered a new type of nucleosomal demonstrating that there is a novel Professor David Tremethick particle that contains not two molecules process of histone variant selectivity The central regulator of eukaryotic gene of H2A.Z per nucleosome (as found whereby either H2A.Lap1 or H2A.Z/H2A transcription is the organisation of the at the centromere) but only one (i.e. a is targeted to a specific promoter. Genes genome into chromatin. Chromatin is heterotypic nucleosome containing both specific for spermatogenesis appear to built from nucleosomes (histones plus H2A/H2A.Z rather than H2A.Z/H2A.Z). receive H2A.Lap1 while H2A.Z is targeted DNA), the universal repeating protein-DNA This new type of nucleosome is highly to house keeping genes. complex in all eukaryotic cells. The tail of unstable and found at active promoters We have shown that the localisation of the each histone protrudes on the outside and other open regions of chromatin. histone variant H2A.Z at active promoters of the nucleosome and is subject to an We have discovered a specific is dynamic during the cell cycle in mouse extensive range of enzyme-catalysed macromolecular determinant (an acidic stem cells and not maintained following modifications. It has been argued that patch) on the surface of a nucleosome DNA replication. During the transition the combination of such modifications is responsible for the ability of H2A.Z to from G1 to M phase, histone H2A.Z is recognized or read by specific chromatin- promote the compaction of chromatin redistributed from active promoters to the binding proteins involved in regulating and the formation of heterochromatin. centromere and subtelomeric regions. transcription and/or chromatin structure. We have recently discovered a new This work shows that remodelling of However, our recent work has shown that H2A histone variant in the mouse that active chromatin occurs during the cell the functional readout of specific histone lacks this acidic patch (which we have cycle, with histone H2A.Z being relocated modifications is not sufficient to control designated H2A.Lap1 - Lack of an to different regions of the genome at chromatin function, but is also dependent acidic patch), and consistent with our different phases. This challenges the upon the composition of the underlying model, incorporation of this variant current view that active transcription nucleosome. into nucleosomes inhibits chromatin marks established in G1 phase remain The biochemical composition of the condensation, in contrast to H2A.Z. Using throughout M phase to facilitate the re- nucleosome is altered by the substitution a high-throughput, deep-sequencing establishment of gene transcription after of one or more of the core histones approach, we have identified this cell division. with the corresponding histone variant. histone variant as a novel chromatin jcsmr.anu.edu.au/research/genome- Our studies have focused on a major component of the Transcriptional Start biology/chromatin-transcriptional- essential variant of H2A, H2A.Z, and Site of active genes expressed during regulation

Annual Review 2012 31 A conceptual biology approach to understanding protein function in animals and plants

insights into protein structure and function methods, the vast resources in seed Department of and develop them into predictions banks and supercomputing power. For for further test by experiment and example for Rubisco re-engineering, we Genome Biology computation. combined insights from our large-scale The effectiveness of this approach at computational studies of the enzyme’s Computational and all stages of the research program is reaction mechanism with phylogenetic illustrated by our rapid progress within analyses from public structural and Conceptual Biology Group current research directed to improving sequence data, allowing us to make photosynthesis in plants, and thus precise predictions of which residues Professor Jill Gready crop yield. Photosynthesis in plants (amino acids) of the protein to mutate We are interested in understanding how converts the freely available resources and to what alternative amino acid. This proteins carry out their functions in the of energy from sunlight and carbon overcomes the limiting combinatorial cell and how they have been sculpted by from atmospheric CO2 into energy-rich problem of which residues to mutate and evolution to do so. Our findings provide biological sugars and O2. This process to what. the basic knowledge to understand underpins all life, plant and animal. The The program is being undertaken within proteins’ normal functions in plants and enzyme Rubisco captures of CO2 into a large conceptual, computer-based and animals, their dysfunctions in disease and sugars, but despite its critical role it experimental program with collaborators how they might be improved by protein has the paradoxical distinction of being in the Research School of Biology and re-engineering. a very slow and inefficient enzyme. the commercial (Bayer Bioscience) Rapid, free online access to huge Two major approaches to improving and not-for-profit (GRDC) agbiotech amounts of biological data in international Rubisco performance in plants are from industries. Although our main aim is to databanks – especially nucleotide and re-engineering of the enzyme itself and address the critical problem of global food protein sequences and structures and introducing the modified gene into the security other potential applications are gene expression data from all kingdoms plant by genetic transformation, or by to material crops, biofuel production, and of life – as well as formal and informal introducing naturally occurring ‘better’ carbon sequestration. We have structured sources of the scientific literature provide variant Rubiscos into the plant by handling of intellectual property (IP) so new means for posing and answering breeding. that in addition to commercialization, research questions. We employ an We have recently developed new unique, the new technology will be available approach, christened conceptual biology and complementary, technologies for at no cost to subsistence farmers in that integrates these data and information both approaches, and validated them lesser-developed countries, assisting in to create hypotheses and initially test in plants. Both use the conceptual improving food security and reducing them. In essence, we re-purpose data biology approach to exploit new poverty. generated by other researchers, and capabilities for integrating sequence jcsmr.anu.edu.au/research/genome- create novel links (“maps”) between data and functional knowledge in public biology/computational-conceptual- of different types. We then interrogate databases and the literature, modern biology the combined data “matrix” to find new gene sequencing and molecular biology

32 The John Curtin School of Medical Research GENETIC VARIATION AND DISEASE

DNA letters (like AA or TT) at ~10bp project. Our statistical models are also Department of intervals imparts a natural twist such that gaining broad acceptance, now being the double-helix now forms a large spiral implemented by authors of other software Genome Biology that facilitates formation of a nucleosome, packages. a fundamental building block of gene jcsmr.anu.edu.au/research/genome- regulation. We have developed statistical biology/computational-genomics Computational Genomics techniques that can identify such Group recurring sequence patterns. An invaluable ingredient to successfully Associate Professor Gavin Huttley identifying important genetic variation Biological functions and processes is a capacity to identify the operation are encoded in our genomes by the of natural selection. This is most specific ordering of DNA nucleotides. straightforward for protein coding DNA Variation in this genome sequence sequences. For instance, mutating one between individuals is a critical factor of the amino acids of haemoglobin in inter-individual differences in disease that is responsible for binding oxygen susceptibility. Why does this variation may prove lethal. Our understanding exist? Why do some genetic variants of how natural selection operates on influence disease susceptibility but not protein coding sequences is facilitated others? Can we distinguish genetic by understanding the encoding system. variants that are likely to affect disease In the aforementioned example we can from those that are not? These are predict the impact on an individual of the questions we seek to address by carrying a genetic variant. For other mathematically identifying patterns in DNA types of information in the genome, like sequences and relating these patterns the sequence elements that facilitate to experimental measures of biological nucleosome binding, the impact of systems. genetic variation remains unknown. A key ingredient to successfully identifying The development of statistical methods patterns in DNA sequence is to have a and algorithms for measurement of DNA good understanding of the biochemistry sequence properties is a major objective of nucleic acids. For instance, the DNA of the Computational Genomics Group. double helix executes one full 360º The results of this work are released as rotation every 10.4 steps of the ladder. open source software. Our software is in This regular periodicity is expected to, use by thousands of researchers across and does, influence how proteins interact the world, including numerous high profile with DNA. Placing specific doublets of studies such as the human Microbiome

Annual Review 2012 33 The Evolution of Human Diversity and its Impact on Health and Disease

We use novel approaches to investigate Department of and analyze the DNA sequence variation in the regions of these genes with a Genome Biology particular focus on variation involving complex repeat structures. We are also developing new approaches to screening Genome Diversity and complex genetic variation in large human Health Group population samples and investigating the impact of this variation on molecular, Professor Simon Easteal cellular and behavioural functioning and Our research addresses fundamental on medical conditions including age- questions about human biology: ‘Why related cognitive decline, dementia and are people so different from each other?’ attention deficit disorder. ‘How have these differences between jcsmr.anu.edu.au/research/genome- people arisen during human evolution?’ biology/genome-diversity-health and ‘How do these differences affect health and susceptibility to disease?’ Our aim is to develop better approaches to managing health and to preventing disease that incorporate knowledge of our peculiar evolutionary past and the biological and psychological differences between people that it has produced. A particular current focus of research is an investigation of variation in the genes that encode the dopamine transporter and an arginine vasopressin receptor.

34 The John Curtin School of Medical Research Translating Well, Translating Productively

as a means of controlling gene activity. through inhibiting the roles of the cap and Department of Translation takes place on cellular nano- poly(A) tail in messenger RNA translation. devices called ribosomes, and is aided by Recently, Preiss and co-workers have Genome Biology numerous accessory factors (Figure 2). incorporated next generation sequencing Control at this translational level and its into their research and now pursue dysregulation is increasingly recognised interests in the area of RNA utilisation with RNA Biology Group as an important factor in human health this technology. This has enabled them and disease. Pathologic mechanisms to profile the occurrence of a modified Professor Thomas Preiss may perturb the entire cellular translation building block called 5-methylcytosine in Our genome is a complex machine program or some specific aspect of it, human cellular RNAs. The importance of churning out a myriad of different RNA leading to, for instance, malignant cell 5-methylcytosine for DNA function is well molecules representing short-lived proliferation in cancer and inappropriate understood, but its role in RNA is as yet ‘working’ copies of individual genomic cell death or growth in cardiac disease. poorly explored. DNA segments, while the genome itself is kept safely in the nucleus of each of our Professor Preiss has made contributions Our Group engages in collaborative cells. A subset of these RNA molecules, to our understanding of how messenger research with scientists around the world called messenger RNAs, encodes RNA translation begins in higher to elucidate processes such as the information for the production of the organisms. Specifically, he was involved generation of induced pluripotent cells for proteins that carry out most of the cellular in identifying key roles of the ends of the stem cell therapy, or to study important functions. The flow of genetic information messenger, called the cap and poly(A) human diseases such as cancer, diabetes from DNA via RNA to protein is key to tail. Another focus is the mechanism by and obesity, Alzheimer’s and heart all life on earth (Figure 1). Research over which a novel class of small noncoding disease. the past decade has shown that most RNAs called microRNAs affects gene jcsmr.anu.edu.au/research/genome- genomic sequences actually do not carry expression. Professor Preiss’ research biology/rna-biology information for the production of proteins has helped establish that microRNAs act but instead give rise to ‘noncoding’ RNAs, many of which are probably regulating the expression and utilisation of the protein-coding genes and messenger RNAs. A core process in this expression of genetic information is the ‘translation’ of the code of messenger RNAs into proteins. Our Group studies the mechanisms and patterns of this mRNA translation and its regulation by RNA- binding proteins and noncoding RNAs Figure 1 Figure2 Selective transcriptome utilisation mRNA as template for translation

Annual Review 2012 35 Department of Immunology

Head of Department

Professor Chris Goodnow

Group Leader Cancer and Vascular Biology Group Professor Chris Parish Cell Biology Laboratory Professor Chris Parish Diabetes/Transplantation Immunobiology Laboratory Dr Charmaine Simeonovic Matrix Biology Laboratory Dr Craig Freeman Immunogenomics Group Professor Chris Goodnow Cell-Mediated Immunogenomics Laboratory Dr Ed Bertram Immune Tolerance & Signalling Laboratory Professor Chris Goodnow Immunogenomics Bioinformatics Laboratory Dr Thomas Dan Andrews Ramaciotti Immunization Genomics Laboratory Dr Anselm Enders Infection and Immunity Group Associate Professor Guna Karupiah Host Defence Laboratory Associate Professor Guna Karupiah Inflammation and Viral Immunopathology Laboratory Dr Geeta Chaudhri Molecular Mucosal Vaccine Immunology Group Dr Charani Ranasinghe Translational Research Unit Dr Matthew Cook (jointly with Canberra Hospital)

36 The John Curtin School of Medical Research New approaches to controlling cancer and autoimmunity

patients. The Group has also shown vaccines completed a promising Phase I Department of that platelets play a crucial role in cancer clinical trials in melanoma patients in 2011 Immunology spread (metastasis) and represent a and is being further perfected. target for the development of new anti- Finally, basic immunological research by metastatic drugs. Heparanase inhibitors the Cancer and Vascular Biology Group Cancer & Vascular Biology have also being investigated as potential has resulted in important advances. First, new anti-inflammatory agents and have a blood borne protein, called histidine- Group been shown to control the development rich glycoprotein, has been identified of Type 1 diabetes in mice. The diabetes which may play an important role in Professor Christopher Parish studies have also revealed that heparan controlling autoimmune diseases, such as The Cancer and Vascular Biology Group sulfate is expressed at extraordinarily systemic lupus, by aiding the elimination is particularly interested in identifying high levels by the insulin-producing cells of dead and dying cells. Second, the novel approaches to controlling cancer in the pancreas and is, in fact, essential Group has discovered a novel form of and autoimmune diseases, such as Type for the survival of these cells. Indeed, membrane exchange between cells I diabetes. When primary cancers arise loss of heparan sulfate from the insulin- of the immune system, which has the they cannot grow beyond 1-2 millimetres producing cells is associated with both potential to dramatically enhance the in diameter unless they induce the growth Type 1 and Type 2 diabetes, although immune response to both pathogens of new blood vessels that supply them via different mechanisms, immune cell- and cancer. Third, recent studies suggest with oxygen and nutrients and remove derived heparanase clearly being involved that heparan sulfate, expressed at high toxic byproducts of metabolism. Similarly, in heparan sulfate loss in Type 1 diabetes. levels by a small subset of stromal cells blood vessels play an important role in the These studies have raised the interesting in the thymus, plays a crucial role in T cell spread of cancer cells to other organs, possibility that heparanase inhibition/ development in the thymus. the cancer cells having to use a range of heparan sulfate replacement therapy degradative enzymes to digest their way could be used as a treatment for Type jcsmr.anu.edu.au/research/immunology/ through blood vessel walls, particularly 1 and Type 2 diabetes. In fact, heparan cancer-vascular-biology when they lodge in distant organs. sulfate-like drugs have been developed that can inhibit diabetes progression and The Cancer and Vascular Biology Group are being prepared for clinical trials in has been able to develop relatively simple Type 1 diabetes patients. sugar-based drugs that inhibit blood vessel growth in tumours and block a In parallel studies the Group is key enzyme, called heparanase, that investigating, in collaboration with the degrades the complex sugar molecule biotechnology company Lipotek, a heparan sulfate and aids cancer spread number of clever vaccination strategies (metastasis). One of these drugs that stimulate the immune system to (Muparfostat) is being currently tested recognise cancer cells as foreign and in a Phase III clinical trial in liver cancer eliminate them. One of these cancer

Annual Review 2012 37 A common mechanism for beta cell failure in Type 1 and Type 2 diabetes

by the degradation of beta cell HS by preserving beta cell survival, thereby Department of heparanase, an HS-degrading enzyme, preserving the insulin-secreting function produced by insulitis mononuclear cells. of islet beta cells. In the clinical situation, Immunology Furthermore, we showed that T1D can this novel therapeutic approach may offer be prevented and beta cell HS can be the major benefits of removing the need preserved by in vivo treatment with a for exogenous insulin therapy in T2D Diabetes/ Transplantation heparanase inhibitor, PI-88. Significantly, and preventing the associated long-term Immunobiology Laboratory we have found that beta cells deficient vascular complications of diabetes. in HS following islet isolation can be Charmaine Simeonovic, Andrew Dr Charmaine Simeonovic rescued in vitro from dying in culture and Ziolkowksi, Sarah Popp, Zuopeng Wu, Type 2 diabetes (T2D) is a “metabolic from free radical-induced damage by HS Craig Freeman and Christopher Parish syndrome” disease characterised by replacement, using HS mimetics. jcsmr.anu.edu.au/research/ insulin resistance, an impaired capacity In situ, HS is conventionally attached for insulin, produced by beta cells in the immunology/cancer-vascular-biology/ to a core protein which together form a diabetestransplantation-immunology Islets of Langerhans in the pancreas, heparan sulfate proteoglycan (HSPG). to facilitate glucose uptake by target Indeed, HS synthesis occurs directly onto tissues such as adipose and muscle. the core proteins and cannot proceed in Insulin resistance leads to hyperglycaemia their absence. Our studies have shown and lipolysis. Initially, the beta cells that normal mouse islet beta cells strongly increase their production of insulin but express a number of HSPGs (including eventually this response together with collagen type XVIII and syndecan-1), the elevated circulating free fatty acids, representing the source of beta cell HS. results in endoplasmic reticulum stress Furthermore, T2D in humans and in the (ER stress). Activation of the unfolded db/db mouse, like T1D, is characterised protein response (UPR) pathway to relieve by substantial loss of HS from islet beta ER stress, dampens protein production, cells. However, T2D is also associated exacerbates insulin insufficiency and, with loss of the intracellular HSPG core without the restoration of homeostasis, proteins from islet beta cells. These leads to beta cell death. The molecular findings raise the possibility that beta mechanism responsible for beta cell cell death in T2D may result from HS death in T2D is unclear. Our paradigm- deficiency. In contrast to T1D, HS loss in shifting studies have demonstrated that T2D beta cells may be secondary to ER islet beta cells contain very high levels stress-induced decline in the production of the complex sugar “heparan sulfate” of HSPG core proteins and hence (HS) and unconditionally require it for their impaired HS synthesis. HS replacement survival. We reported that Type 1 diabetes using HS mimetics early in T2D disease (T1D) in NOD mice is characterised could therefore play a vital role in

38 The John Curtin School of Medical Research Immune regulation

Highlights in 2012 include: spearheaded a multidisciplinary effort Department of The discovery by Yogesh Jeelall and with the APF and the NCI supercomputer Dr Keisuke Horikawa that common facility that successfully achieved this Immunology mutations in human lymphoma re-wire the milestone. They developed the methods way B lymphocytes respond to normal by analysing families of mice genetically Immunogenomics Group components of our body. Normally, identical except for approximately fifty B cells carrying antibodies that react inherited mutations scattered across the hundred million DNA bases of their Professor Chris Goodnow with self – so-called “autoantibodies” – are stimulated to commit cellular exome. The team’s mutation detection The group discovers molecular and suicide, ensuring the immune system pipeline has already produced tens of cellular mechanisms and genes regulating does not attack our own body. But thousands of new mouse models for the immune response: when these B cells acquired a mutant the world research community to study consequences of individual mutations, >> to prevent autoimmunity against form of the CARD11 gene, as often self antigens (eg lupus, diabetes, occurs in non-Hodgkin’s lymphoma, and enabled Associate Prof Matthew rheumatoid arthritis, thyroiditis) and the “forbidden clones” completely Cook and Professor Carola Vinuesa allergy; switched their response: instead of dying to identify inherited human mutations they responded by growing, copying explaining immunological diseases in their >> to prevent uncontrolled growth of patients. lymphoid malignancies (leukemia, themselves over and over, and secreting lymphoma and myeloma); autoantibody into the bloodstream. These One fruit of the new mutation analysis findings illuminate how the body normally pipeline was discovery of a new gene and >> to promote immunity and avoids autoimmunity, how lymphoma immunological memory against mechanism governing the survival of B develops, and a potential explanation viruses and bacteria (immunisation lymphocytes, led by Hannes Bergmann for the co-occurrence of autoimmune and immunological memory). and Dr Anselm Enders. They found that disease and lymphoma. mutations eliminating a protein-cleaving We aim to answer central questions Mutations, like needles in a haystack, enzyme, SPPL2A, render B cells unable about the mechanisms of tolerance and were notoriously difficult to detect to display on their surface two types of immunity in B and T cells, and to create and study. A goal thought technically receptors needed to keep the B cells a collaborative environment where the impossible three years ago was to read alive in the circulation and lymph glands. next generation of scientific leaders can all of the DNA sequences that code for This discovery illuminates an entirely new establish independent lines of research proteins making our body - comprising biochemical pathway specifically required while drawing upon shared expertise and 100 million DNA letters called the “exome” for B cell survival, and a promising target resources. We develop and use state- - and accurately detect misspelling (single for new drugs to eliminate the unwanted of-the-art methods from mouse and nucleotide variants) when present at rates B cells responsible for lymphoma or human molecular genetics and genomics, of only one error in a million letters. In autoimmune disease. biochemistry and cell biology, cell a major advance Dr Dan Andrews and jcsmr.anu.edu.au/research/immunology/ signalling, cellular immunology and clinical the bioinformatics team he assembled immunogenomics immunology.

Annual Review 2012 39 Studies of IMMUNISATION and Infection

genes and pathways in B-lymphocyte A further focus of the lab is the Department of development and function we screen investigation if genes identified in the mice after random ENU mutagenesis ENU screens contribute to the disease Immunology for defects in the development of of patients with immunodeficiencies. B-lymphocytes, or the generation of an We also try to better understand the immune response after immunisation. phenotype of patients by careful analysis Ramaciotti Immunization Once a strain is identified we find the of appropriate mouse models. These Genomics Laboratory causative mutation by sequencing all studies are carried out in cooperation with exons in an affected animal. Over the last clinicians from the University of Freiburg, Dr Anselm Enders few years this approach has led to the . The Ramaciotti Immunization Genomics establishment of more than 30 different jcsmr.anu.edu.au/ramaciotti- Laboratory was established in 2008 strains, and the unexpected discovery immunization-genomics through a Major Initiative Award from the that a defect in a widely expressed Clive and Vera Ramaciotti Foundation to transporter of specific phospholipids Dr Anselm Enders and Professor Chris called ATP11C leads to a defect in the Goodnow. The laboratory focuses on early development of B-lymphocytes. elucidating the genes and mechanisms Further defects found in these mice controlling the development and function included a defect in the survival of red of the immune system with a special blood cells and also the development of focus on B-lymphocytes. Normal liver tumors. We are currently following up development of B-lymphocytes and on this discovery to identify the molecular the production of antibodies by them is pathways that are dependent on the essential for protection against recurrent phospholipid composition of the cell infections, and the protection provided membrane. by most currently employed vaccines. We also discovered that a protein (called Any defect in the genetic control of SPPL2A) of previously unknown in vivo B-lymphocyte development or function function is essential for the normal survival can lead either to immunodeficiency, of mature B cells. At the moment we try autoimmunity or B cell malignancy. to understand what causes the survival Because of this importance, the defect and if this dependence of mature B generation of B-lymphocytes is one of the cells on SPPL2A could be used for future most thoroughly studied mammalian cell treatments of B cell malignancies or B cell developmental systems. Despite these mediated autoimmune diseases. efforts, key steps required to shape the mature B-lymphocyte compartment are yet to be discovered. To identify novel

40 The John Curtin School of Medical Research New strategies to fight viral diseases

its natural host to characterise critical well-established anti-cancer drugs can be Department of features of long-term humoral immunity used as antiviral agents. Immunology to virus. We are defining the attributes of We are using a systems biology approach viral antigen that elicit the most efficacious to understand immune regulatory antibody responses, and which lead to networks in antiviral immunity. Novel Host Defence Laboratory optimal induction and maintenance of regulators of the innate and adaptive long-term humoral immunity. immune responses to poxviruses are Associate Professor Guna We have recently shown that expansion being elucidated using forward genetics, Karupiah of virus-specific CD8 T cell clones can ENU mutagenesis and systems biology. occur via recruitment of CD8 T cells (of The aim is to reveal the signaling and Our research program uses mouse irrelevant specificity) through TCR sharing. gene regulatory networks that underpin models of viral infections, which are We are investigating how universal this the immune response to infection, and validated to predict human immune antiviral strategy is, the ground rules then to verify the relevance to humans of mechanisms, to study both innate and for TCR sharing during an infection any newly identified genes in mice. adaptive immunity to infection. This and whether this hitherto unrecognised enables us to establish strong causal The overall aim of our research program mechanism can be harnessed to relationships and map the requirements is to gain a better understanding of the overcome disease in which CD8 T cells for protection against viral infections in a immune response to viral infections, play an important role. way that is not possible in humans. We which will be key to developing novel are studying innate, cell-mediated and As the outcome of an infection is therapeutic and vaccination strategies to antibody responses to both primary and dependent on the interaction between combat viral diseases. secondary viral infection with the aim of viral and host genes, we are also jcsmr.anu.edu.au/research/immunology/ determining the correlates of protective investigating how some virus-encoded infection-immunity/host-defence immunity. This is done using wildtype immune evasion molecules subvert or and recombinant viruses (orthopox, dampen the host antiviral response. orthomyxo, herpes) in combination with These studies will not only provide a wildtype, gene knockout, gene knockin, better understanding of the workings of TCR transgenic, BCR transgenic and the immune system but will potentially ENU mutant mouse models. This year pave the way for utilisation of recombinant we have made progress in a number of virus-encoded proteins to treat certain areas, of which five are highlighted. chronic inflammatory diseases. Much of our current understanding of the We are investigating the contribution induction and maintenance of long-lived of actin-based motility to (i) virus antibody response is based on studies pathogenesis and (ii) viral spread within using non-replicating model antigens. a natural host. We are targeting the We are therefore using a well-established Abl-family kinases to assess these model of orthopoxvirus infection in processes. Our goal is to assess whether

Annual Review 2012 41 The race to fight infection

evolved to subvert the host immune in our laboratory and we believe it Department of response. constitutes a major route through which Immunology It is well accepted that both resident and information transfer occurs when TNF recruited macrophages are involved in receptors (TNFR) bind to membrane TNF. initiating and maintaining inflammation Of the strategies used by viruses to Inflammation and Viral in response to infection. More recent attenuate the host response, many are studies point to a role for these cells in directed toward interfering with TNF Immunopathology regulating the switching off mechanisms function, thus implicating this cytokine Laboratory in the resolution of inflammation, once as an important player in virus-host infection has cleared. Thus resolution interactions. Poxviruses, including Dr Geeta Chaudhri of inflammation and return to tissue ectromelia virus, encode molecules Our research is directed towards a better homeostasis is now thought to be an homologous to TNFR. Using this understanding of virus-host interactions active and coordinated process which model, we have found that host TNF is and the immune response to infection terminates the processes involved up regulated during infection and that with a view to develop more effective in the inflammatory response. There membrane TNF plays a role distinct vaccines and selective treatments that is now growing evidence that the from soluble TNF in the response to would minimise the damaging effects of ability of macrophages to modify their infection. This is due, in part, to the an established infection. We are pursuing function based on the changing signals ability of membrane TNF to participate in this goal using a range of viral (for from their environment, and switch reverse signalling. Further, virus encoded example, pox and influenza A) and animal from M1 to M2, is an essential step TNFR utilises the same pathways models. Our studies allow us to dissect in the resolution of inflammation and as soluble host TNFR to modulate the roles of leukocyte subsets, cytokines, pathology. We are investigating this immunopathogenesis, during this antibody and a number of signalling process and the mechanisms involved in infection. molecules in viral infection and disease. immunopathology as well as resolution of We are investigating the possibility The immune effector mechanisms that viral disease. that recombinant viral proteins, which are generated to control and clear virus A major area of focus has been the have been engineered by nature instead often cause immunopathology cytokine tumour necrosis factor (TNF); through evolution to limit the immune that has serious, sometimes lethal, expressed in both soluble and membrane response and inflammation, may be consequences for the host. We have forms. We have demonstrated that used as therapeutic agents to combat therefore directed our research effort membrane TNF participates in reverse diseases where inflammation and toward dissecting out the immunological signalling, a process whereby interaction immunopathology are a problem. parameters that allow the rapid resolution with its receptor leads to the transmission jcsmr.anu.edu.au/research/immunology/ of virus infection with minimum pathology. of signal in the direction of the cell These studies are being carried out in infection-immunity/inflammation-viral- expressing membrane TNF. The biological immunopathology parallel with others that attempt to reveal outcomes, resulting from activation of this the many strategies that viruses have pathway are currently being elucidated

42 The John Curtin School of Medical Research Novel vaccine against HIV-1

to induce good protective immunity, a Department of vaccine should target the “quantity” or the “quality” of immunity generated against Immunology the virus. Our studies have revealed that mucosal Molecular Mucosal Vaccine delivery can induce T cells of higher quality with better protection compared Immunology Group to systemic delivery, and this is related to the induction of HIV-specific killer T cells Dr Charani Ranasinghe that express lower amounts of IL-4 and Thirty years have passed since the IL-13 cytokines. Our studies indicate that discovery of HIV/AIDS and still there is these cytokines play an important role in no cure for the disease. The health and dampening vaccine efficacy. Therefore, in financial burden to countries in sub- our laboratory we have now developed Saharan Africa or South East Asia to several novel vaccines that transiently contain the infection means that an HIV block IL-4/IL-13 activity at the vaccination vaccine is the best cost effective strategy site. We have found that these vaccines and also the only long-term solution. induce excellent high “quality” killer HIV-1 is first encountered via the genito- T cells in the mucosal and systemic rectal mucosae, and primary CD4+ T compartments with good protective cell loss occurs in the gut mucosa prior efficacy. We are currently in the process to dissemination of virus into the blood of a) understanding the exact molecular compartment. Hence, a vaccine that can mechanisms how these vaccines work induce immunity at these primary sites and b) translating our work into the next of infection (rectal, vaginal sites) would phase of development, with the hope of most likely be the best strategy in the taking our work into a future clinical trial. fight against HIV/AIDS. We have found that to generate long-lived mucosal jcsmr.anu.edu.au/research/immunology/ immunity, a vaccine has to be delivered molecular-mucosal-vaccine- via the mucosal route (i.e. intranasal, intra immunology rectal, oral routes). Interestingly, many of the HIV-1 vaccines delivered purely to the blood compartment (systemic delivery) have elicited high magnitude of T cell immunity in animal models, but have failed to translate effectively into humans. Thus, this has raised the debate whether

Annual Review 2012 43 Studies on Diseases of the Immune System

Experience from the clinic suggests that of autoimmunity (Lupus and Sjogren’s Department of elucidation of one class of disease will be syndrome, APOSLE study), primary informative for the others. For example, immune deficiency cohort (ANZADA Immunology autoimmunity and immune deficiency study). Recruitment for each of these often cluster in the same family, or even studies is continuing. In the past few the same individual. Specific areas years, we have made significant progress Translational Research Unit of investigation are primary antibody in understanding the cellular basis deficiency and hyper IgE syndromes for each of these classes of immune- Associate Professor Matthew (immune deficiency diseases), systemic mediated disease, particularly with regard Cook lupus erythematosus and Sjogren’s to defects in memory T cell subsets The Translational Research Group works syndrome (autoimmune diseases), and that cause both immune deficiency and at the interface between fundamental regulation of Th2 immune responses autoimmunity. biology and clinical research in order to (allergy), and sarcoidosis. jcsmr.anu.edu.au/research/immunology/ advance our understanding of diseases Our approach involves taking clues from translational-research pathogenesis. In this way, we hope to hypothesis-free, genomic analysis of make progress that will improve the relevant disease phenotypes, especially diagnosis and treatment of immune- by next generation sequencing. We mediated diseases. then test these hypotheses of causation The diseases we work on fall into three by cellular and biochemical analysis. main categories: immune deficiency, Investigations in human subjects, where where pathology results from failure to opportunities to manipulate immunity are mount a sufficient or appropriate immune necessarily far more restricted than it is in response to a pathogen, resulting animal models, nevertheless, confirmation in unusual susceptibility to infection, that the same mechanisms hold in human hypersensitivity diseases (such as disease is essential if we are to make allergy), where pathology results from progress towards new diagnostics and quantitative or qualitative aberrations in therapeutics. immunity to environmental antigens (eg We are fortunate to have extensive clinical pollen or foods), and autoimmunity, where collaborators from around Australia, pathology results from immune response and internationally. We have established to host antigens. substantial patient cohorts in the areas

44 The John Curtin School of Medical Research Department of Pathogens & Immunity

Head of Department

Professor Carola Vinuesa

Group Leader Humoral Immunity and Autoimmunity Group Professor Carola Vinuesa

Annual Review 2012 45 GENERATING ANTIBODY RESPONSES TO PREVENT AUTOIMMUNITY AND TO FIGHT INFECTION

long-lasting immunity, and identifying ultimate goal is to develop new ways Department of genetic abnormalities that interfere to harness Tfh and Tfr cells to generate with this process and contribute to the effective vaccines against life-threatening Pathogens & development of autoimmunity. infections and prevent or even treat Immunity The interaction of B cells and a subset autoantibody-mediated diseases and T/B of T-cells known as follicular helper cell lymphomas. T-cells (Tfh cells) within structures called jcsmr.anu.edu.au/research/pathogens- Humoral & Autoimmunity germinal centres, results in the selection immunity/humoral-immunity- of mutated B cells that can produce autoimmunity Group more potent antibodies. These B cells then develop into long-lived antibody Professor Carola Vinuesa producing cells that are responsible for Long-lasting antibody responses are immunological memory and fighting a key component of the mammalian off infections. Our work in the last few immune system that protect us from the years has helped unravel fundamental constant challenge of pathogenic bacteria several aspects of Tfh cell and germinal and viruses. The quality of these antibody centre biology, and demonstrated how matters: effective protection against overactive or excessive numbers of Tfh viruses, bacteria and their lethal toxins cells lead to pathogenic autoantibody requires production of antibodies with production in the autoimmune diseases high affinity. Affinity improvement occurs mentioned above. We have discovered as a consequence of random mutation potent cell-extrinsic and intrinsic targeted at the genes that encode for mechanisms that control Tfh cell the B cell receptor. However, this ability numbers: T follicular regulatory (Tfr) cells to produce long lasting high affinity extrinsically limit Tfh cells and germinal antibodies is a double-edged sword, as center B cells whereas for example, the perturbations can result in autoimmune Roquin gene intrinsically controls Tfh diseases. These diseases include lupus, cells by repressing mRNAs important for Type 1 diabetes, rheumatoid arthritis, Tfh accumulation. The balance between thyroiditis, Sjogren’s syndrome and Tfh and Tfr cells appears to be key to typically occur when the immune system control both quantity and quality of cannot differentiate between invading antibody responses, and may influence pathogens and the body’s own cells, survival of B and T cell lymphomas. Our resulting in the destruction of these cells. current focus lies in the identification Our research is unraveling the complex of novel posttranscriptional pathways interaction of cells and molecules that that control the Tfh:Tfr balance. Our regulate the production of potent,

46 The John Curtin School of Medical Research Department of Molecular Bioscience

Head of Department Professor Phil Board (until September) Professor Angela Dulhunty (from September)

Group Leader Biomolecular Structure Group Dr Marco Casarotto Cancer Metabolism and Therapy Group Dr Anneke Blackburn Cardiac and Skeletal Muscle Proteomics Group Dr Nikki Beard Cytokine Molecular Biology and Signalling Group Professor Ian Young Epigenetics and Genome Stability Group Dr Danny Rangasamy Molecular Genetics Group Professor Phil Board Muscle Research Group Professor Angela Dulhunty Stem Cells and Gene Targeting Group Professor Klaus Matthaei

Annual Review 2012 47 Drug Design

physiology, microbiology, biochemistry, is an exciting area and critical to the Department pharmacology, drug design/delivery development of new therapies. We aim and molecular biophysics. Listed below to combine our expertise in epigenetics, of Molecular are some of the projects that are being cancer, pathology, structural biology and Bioscience studied. drug design to demonstrate that various The dihydropyridine and ryanodine enzymes are novel epigenetic regulator receptors (DHPR &RyR) play essential of human cancers, and propose a clear Biomolecular Interactions roles in muscle function and my and integrated translational strategy to contribution has been to determine treat cancers with novel small molecule Group how these proteins signal to each other inhibitors. Using a multidisciplinary in skeletal excitation-contraction (EC) approach underpinned by internationally Associate Professor Marco coupling. Because the protein machinery competitive basic science, we will be able Casarotto present in skeletal and cardiac muscle to apply our novel studies on epigenetic The main focus of the work in my is very similar, it is important to identify regulation to personalised approaches to laboratory has been to explore the diverse key differences in the makeup and therapy. structural and physical properties of function of these two systems. The 15 Virions or virus ion channels are small biomolecules in order to gain a greater kD intracellular II-III loop region of the membrane proteins capable of forming understanding of the physiological roles DHPR is implicated in skeletal muscle multimeric ion channels and they are they play in the body. A number of diverse function and we have been responsible expressed in a number of viruses structure-based strategies including for elucidating the first high resolution including influenza A (M2), HIV-1 (Vpu) nuclear magnetic resonance (NMR) structure study of this region. We and Hepatitis-C (P7). We have developed spectroscopy, molecular biology, protein- have also determined that the skeletal a strategy that employs surface plasmon engineering and rational drug design β-subunit of DHPR has distinct interactive resonance techniques to measure the techniques are employed to address properties compared with its cardiac affinity of a number of antiviral drugs to important biological questions. A wide counterpart. This work has laid the these ion channels and in the case of range of medically relevant projects are foundation for us to propose a series of the M2 and Vpu ion channels, have used carried out, all designed to provide a novel hypotheses that are currently being this technology to elucidate the mode of unique insight into the role that specific evaluated not only in my laboratory but binding of various drug compounds. biomolecules play in a number of disease world-wide. jcsmr.anu.edu.au/research/molecular- states. By understanding these roles it Epigenetic enzymes activate or silence bioscience/biomolecular-interactions is then possible to identify and design genes by epigenetically ‘tagging’ the novel therapeutic agents for particular amino terminal tails of histone proteins diseases. This work has been published and are critical molecular mediators of in diverse biological and chemical journals a number of biological processes. The that reflect the broad application of our contribution of epigenetic enzymes research and encompass areas such as in the regulation of human cancers

48 The John Curtin School of Medical Research Targeting the Sweet Tooth of Cancer

minimal side effects, and therefore has hormonal drug effective in breast cancer Department potential to move rapidly into the clinic prevention would greatly improve the for use in cancer treatment. We have outlook and quality of life for women of Molecular demonstrated that dichloroacetate is able carrying mutations in breast cancer Bioscience to stop the growth of metastatic breast predisposition genes. cancer cells both in vitro and in vivo in jcsmr.anu.edu.au/research/molecular- animal models. bioscience/cancer-metabolism-genetics Cancer Metabolism and While dichloroacetate alone does not kill breast cancer cells, taking away the drive Genetics Group to grow makes the cells more likely to die when co-treated with existing anti- Dr Anneke Blackburn cancer drugs. This could mean the dose It was first recognised in the 1930s that of current anti-cancer drugs could be cancer cells use glucose differently to lowered, thus reducing toxic side effects normal cells. Normal cells use oxygen to but without loss of effectiveness. We are metabolise glucose for energy production, currently investigating which drugs DCA whereas cancer cells preferentially works best with. metabolize glucose for the production of cellular building blocks via a pathway We are also interested in the genetic that does not require oxygen and results factors that contribute to breast in the accumulation of lactic acid. Other cancer susceptibility, and in the aspects of metabolism in cancer cells outcomes for women identified with also differ from normal tissues, and very high predisposition for developing these differences are yet to be exploited breast cancer. We are investigating for therapeutic purposes. The Cancer whether modifying metabolism with Metabolism and Genetics Group is dichloroacetate or other non-toxic drugs studying the effect of redirecting cancer can prevent or delay the development metabolism on the growth and death of of breast cancer in mice genetically breast cancer cells. We are particularly predisposed to developing cancer. These interested in dichloroacetate (DCA), mice carry a mutation in the tumour an old drug that inhibits the anaerobic suppressor gene p53 and are a model metabolism of glucose to lactic acid. This of the multiple tumour syndrome, Li- drug has been used for many years in Fraumeni Syndrome. Experiments such patients with a rare metabolic disorder as this take several years to complete, and so it is known to be safe and have but the discovery of a low toxicity, non-

Annual Review 2012 49 Control of Muscle Contraction by Calcium

understood and underlie the broad aim of breast cancer. Side effects of treatment Department our research. with anthracyclines include severe cardiotoxicity and sudden cardiac death. We are pursuing three main research of Molecular We are investigating how anthracycline themes treatment changes the function of Bioscience 1. Determining how communication proteins in the luminal calcium signalling between proteins in the luminal pathway and how these change result in calcium store facilitates skeletal muscle the cardiotoxic side effects. Cardiac and Skeletal Muscle contraction. Communication between jcsmr.anu.edu.au/research/molecular- the skeletal isoforms of CSQ and RyR Proteomics Group bioscience/cardiac-and-skeletal- is a key determinant of skeletal muscle muscle-proteomics Dr Nikki Beard contraction and essential for normal The Cardiac and Skeletal Biochemistry calcium signalling. We use a biochemical Laboratory investigate how control of approach to uncover the protein binding the luminal calcium store deep inside a partners and specific interaction sites muscle cell leads to muscle contraction. which support this communication. Muscle contraction occurs due to a 2. Investigating how changes in store cascade of events and relies on calcium load or in RyR function lead to heart release from luminal stores. The four main failure. Heart failure is a complex cogs in the luminal calcium signalling multimodal disorder, affecting 2% of pathway are the calcium binding protein the adult population at one time in their calsequestrin (CSQ), the ryanodine life. Heart failure is characterised by receptor (RyR) calcium release channel, disturbances of the luminal calcium store and two linking proteins, triadin and and alterations in how the RyR releases junctin, which bind CSQ to the RyR. calcium. We are investigating how cellular Control of the luminal calcium store changes which occur in heart failure in muscle is vital; disturbances in the alter the calcium stores ability to handle process can lead to potentially fatal calcium and are defining how these skeletal and cardiac conditions, including effects translate into changes in RyR malignant hyperthermia, inclusion-linked calcium release. skeletal myopathy and heart failure. Despite their essential role in skeletal 3. Understanding how chemotherapeutic muscle and the heart, the functional agents cause store calcium disturbances and structural interactions between the and toxicity the heart. Anthracyclines luminal calcium signalling proteins that are highly effective chemotherapeutic contribute to muscle function are poorly agents used to treat leukaemia and

50 The John Curtin School of Medical Research CYTOKINES REGULATE BLOOD CELL DEVELOPMENT: IMPLICATIONS FOR ALLERGY, ASTHMA AND LEUKEMIA

and how these interactions initiate Department signals across the cellular membranes. We have previously determined the 3D of Molecular structure of the main signalling receptor (hbc) shared by these cytokines using Bioscience X-ray crystallography (collaboration with Paul Carr and David Ollis, ANU) and are continuing with the structural Cytokine Molecular Biology biology of cytokine-receptor complexes. and Signalling Group Our recent studies with James Murphy (Walter & Eliza Hall Institute of Medical Professor Ian Young Research, Melbourne) have revealed two Asthma is now recognised as a different modes of receptor activation heterogeneous disorder, in which which influence whether blood cell- subgroups of patients can be defined on forming stem cells undergo maturation the basis of the profile of inflammatory or self-renewal in response to IL-3. By cells in the airways and on their response elucidating the mechanisms controlling to therapy. In asthma, the symptoms blood cell maturation we aim to develop are caused by an allergic reaction in the new treatments to control inflammation lung and the production of inflammatory in asthma (collaboration with Paul cells. The inflammatory cells include Foster, University of Newcastle) and to CD4+ T helper-2 lymphocytes (Th2 understand the involvement of the IL-3 cells), eosinophils, mast cells, basophils, receptor system in myeloid leukemia neutrophils and macrophages, all (collaboration with Professor Y Chen, of which have all been linked to the Fujian Medical University, China). pathogenesis of asthma with different cell jcsmr.anu.edu.au/research/molecular- subsets predominating in specific asthma bioscience/cytokine-molecular-biology- subtypes. We are studying the role of signalling three hormone-like proteins (cytokines; IL- 3, IL-5 and GM-CSF) which stimulate the expansion of inflammatory cells in asthma and may also have a role in leukemia. The cytokines bind to cell surface receptors and influence the growth, maturation and activation state of blood cells. Our aim is to elucidate the molecular details of the cytokine-receptor interactions

Annual Review 2012 51 Mobile DNA element as a marker for early breast cancer detection

tissues, the expression of L1 proteins is technology combined with microarray Department completely absent throughout the cell analysis, we have recently identified a cycle. In contrast, it is overexpressed in class of small non-coding endo-siRNAs of Molecular several clinically relevant breast cancer as a key regulator of L1 retrotransposons tissue specimens. The unchecked L1 in the human genome. Currently, we Bioscience activity would create havoc in the human are testing the epigenetic role of endo- genome, initially through insertional siRNAs including DNA methylation, mutations and later by genomic packaging retrotransposons into inactive Epigenetics and Genome instability through high levels of double- heterochromatin structures, and RNAi- Stability Group strand DNA breaks, deletions, and mediated silencing pathways. This genomic rearrangements. Although the research project will shed new light Dr Danny Rangasamy mechanistic pathways that activate L1 into how and why disease states arise Breast cancer is the most common expression are not known, its expression in breast tissues and how the altered malignant disease in women. The and its effect on genomic instability expressions of L1 retrotransposons worldwide incidence of breast cancer have given rise to suggestion that it may activate the process of breast cancer continues to rise, and has become a serve as useful biomarkers in the early development. Unravelling the relationship leading cause of cancer deaths. There diagnosis of breast cancer or in the between small regulatory endo-siRNAs is an urgent need to discover new prediction of cancer onset. Specifically, and DNA methylation in the development biomarkers for early detection as well as L1 biomarker is useful in the prediction of cancers may provide new strategies to identify new pathways or targets for of genetic changes associated with the for future therapeutic and diagnostic drug therapy. More than 90% of breast transition from normal to hyperplasia to approaches. cancers are sporadic or acquired somatic insitu breast carcinoma to invasive breast jcsmr.anu.edu.au/research/molecular- mutations. It is believed that genomic cancer. With collaboration of the ACT bioscience/epigenetics-genome-stability instability might promote the accumulation Pathology, Canberra Hospital, we are of genetic changes in apparently normal currently testing this L1 biomarker using breast tissue, even before histological a panel of archived breast cancer tissues abnormalities are detectable. Although and confirming the association of L1 genomic instability is commonly found in expression with clinical and morphological invasive carcinomas, little is known about features of breast cancer samples. the timing of critical changes in early Given the deleterious nature of tumorigenesis or changes associated retrotransposon activity and genomic with the transition from normal cells to instability in breast cancer development, primary breast carcinoma. We have we are interested in the mechanisms recently identified mobile DNA elements by which the L1 retrotransposon is “LINE-1 retrotransposons” that are regulated in normal healthy cells, but not differentially expressed in normal and in cancer cells. Using deep-sequencing breast cancer tissue. In normal healthy

52 The John Curtin School of Medical Research Personalised medicine

foreign chemicals and oxidative stress. new structural family. Other members of Department The glutathione transferase (GSTs) family the GGCT family of enzymes are involved of enzymes exhibit a wide range of in the break down of blood clots in of Molecular genetic variability that has been shown mammals and the synthesis of antibiotic Bioscience to impact directly on the metabolism of molecules in some micro organisms. anticancer drugs and to influence the jcsmr.anu.edu.au/research/molecular- onset of asthma as well as Parkinson’s bioscience/molecular-genetics and Alzheimer’s diseases. We are Molecular Genetics Group currently studying the metabolism of dichloroacetic acid (DCA) by glutathione Professor Philip Board transferase Zeta. DCA has been proposed as a novel anticancer drug It has been reported that adverse drug and has applications in other metabolic reactions are the fifth most frequent disorders such as lactic acidosis. In other cause of death. Drugs that are effective studies of the glutathione transferases in in most people but are extremely toxic collaboration with the Muscle Research in a small number of individuals cannot Group we have shown that a Mu class be used unless the patients in whom GST (GSTM2-2) is a potent regulator of toxicity is likely to occur can be identified. the cardiac ryanodine receptor. We are The Molecular Genetics Group studies currently investigating the possibility that genetic differences between individuals peptides derived from GSTM2-2 may in their ability to breakdown and detoxify be useful in treating life threatening heart therapeutic drugs or other environmentally failure. We are also studying the gamma- derived chemicals. In order to understand glutamylcyclotransferase (GGCT) family the significance of the genetic differences of enzymes that are involved in regulating we utilise a variety of molecular glutathione concentrations. GGCT is technologies ranging from the expression highly expressed in some tumours and we of human enzymes in bacteria, X-ray are currently investigating the significance crystallography to determine protein of this as a diagnostic tool. Because of its structures, and the generation of gene role in regulating glutathione synthesis we deficient mice, (with the Gene Targeting are testing GGCT inhibitors to determine Group), as models of human disease. if they will be suitable for the treatment of Our work is particularly focused on the glutathione synthetase deficient patients investigation of the structure and function who have no specific treatment options. of enzymes that synthesise and utilise We have discovered that GGCTs are wide glutathione, a small molecule found in all spread in nature and are members of a living cells that helps to protect against

Annual Review 2012 53 Muscle receptor physiology

The research of the Muscle Group falls The third area is the elusive problem of Department into three areas. The first is excitation- how proteins that are located right inside contraction (EC) coupling which allows the calcium ion store can regulate RyR of Molecular an electrical signal on the cell surface activity in a manner that depends on to release calcium from its internal store the amount of calcium stored, to ensure Bioscience though the RyR. EC coupling depends that fewer calcium ions are released if on interactions between the RyR and a the store is depleted. To understand this dihydropyridine receptor (DHPR) calcium problem, we isolate the individual proteins Muscle Research Group channel in the surface membrane. In and then reconstruct the protein complex the heart this enables RyR activation by that they form with the RyR, at the same Professor Angela Dulhunty calcium ions that enter from outside the time controlling calcium concentration in The Muscle Research Group studies cell through the DHPR. In skeletal muscle the store and measuring the ionic current molecular interactions between proteins there is a depolarisation-dependent signal flowing through the RyR ion channel. that reside inside muscle cells and that transmitted from the DHPR to the RyR by come together to form a molecular jcsmr.anu.edu.au/research/molecular- direct interactions between the proteins. bioscience/muscle-research machine which provides fuel in the Despite years of investigation, we still form of calcium ions to drive skeletal do not know which parts of the proteins muscle contraction and cardiac output. interact to achieve the coupling. The central protein in this machine is a calcium ion channel known as The second area is the changes in the a ryanodine receptor (RyR) which is ryanodine receptor that lead to heart and located in the membrane of a calcium ion skeletal muscle disease. There are many store deep inside the muscle cells. The risk factors for these disorders including calcium ion channel is essential for life smoking, diet, obesity and exercise as because contractile force generated by well as chemotherapy. In addition, there the muscle depends on highly regulated are risk factors that we are born with, cyclical changes in the calcium ions which include genetic changes in the RyR that are available to bind to contractile and the molecules that control its ability proteins to allow them to generate muscle to open and release calcium ions. We force. The operation of this calcium are working to understanding how these ion channel is compromised in skeletal factors impact on RyR function. We have muscle myopathies and in acquired heart discovered that a natural enzyme which and skeletal muscle disease, as well as is present in all muscle cells is a potential with genetic defects that severely affect pharmacological agent for treating heart muscle function. failure and we are refining the molecule for better therapeutic potential.

54 The John Curtin School of Medical Research Gene Targeting and Transgenics

cells as well as normal cells. Breeding the providing the potential for completely new Department chimæra with a normal mouse gives rise treatments of current therapy resistant of Molecular to offspring that carry the modified gene, hypertension. thus creating an animal that is identical jcsmr.anu.edu.au/research/molecular- to the original mouse strain except that bioscience/stem-cells-gene-targeting Bioscience the function of a single gene has been deleted. Similarly, it is also possible to add new genes into mouse embryos resulting Stem Cells & Gene in “transgenic” mice that then have Targeting Group overactive genes. Over the years we have generated a Professor Klaus Matthaei series of different mouse mutant strains Medical research seeks to understand that have been used in mouse models of how gene function is altered in human asthma, gut allergy, nerve re-generation, disease and then treat it. However, it parasite-host relationships, wound is often impossible to perform studies healing, drug de-toxification, muscle directly in the human and we therefore diseases and cancer. More recently, in use a more manipulable system such collaboration with Professor Caryl Hill as the mouse. Since we know the in the Blood Vessel Group we have nucleotide sequence of many genes, it been focusing on the 20-30% of people is now possible to make changes to the that have uncontrolled hypertension corresponding endogenous gene of an because they are unresponsive to embryonic stem (ES) cell and produce a current treatments. We have therefore mouse that carries a desired mutation. generated new hypertensive mice that This procedure is called gene targeting. are transgenic with genes not previously Gene targeting involves the use of DNA associated with hypertension. Importantly, technology to modify a cloned gene, we have developed a new technique which is introduced into the ES cells and with which it is possible to switch these the mutated form replaces the normal specific transgenes genes “on” and “off” gene. The modified ES cells are then in small branches of arteries of mice and microinjected into a blastocyst and they we see that these genes are involved in become integrated. These “combination” controlling blood pressure. Once we fully blastocysts are re-implanted into pseudo- understand this process, we may be able pregnant mice and chimæric offspring are to design small molecules that modify born that consist of the injected modified the function of these genes, thereby

Annual Review 2012 55 Department of Translational Medicine

Head of Department

Professor Julio Licinio

Group Leader Pharmacogenomics Group Professor Ma-Li Wong Translational Endocrinology Team Dr Gilberto Paz-Filho Translational Genomics Group Associate Professor Mauricio Arcos-Burgos Translational Medicine Group Professor Julio Licinio Translational Psychiatry Team Dr Claudio A Mastronardi

56 The John Curtin School of Medical Research CONCEPTUALISATION of a predictive framework for MDD

(i) Eleven fit a dominant model: rs6205 Genotypes and Phenotypes (dbGaP) that Department of (HSD3B1), rs4603 (PSMB4), rs1065756 provides access to large genetic and (ALDH9A1), rs769026 (PDLIM5), phenotypic datasets (1,862 MDD patients Translational rs4648072 (NFKB1), rs4723010 (INMT), and 1,857 unaffected controls). Medicine rs4988496 (GHRHR), rs2229125 We employed ARPA to test high (ADRA1A), rs6265 (BDNF), rs4318 (ACE), order gene-gene and gene-covariates rs3744793 (USP36), and rs6267 (COMT). (demographic data) interactions. It is Pharmacogenomics Group (ii) Six best fit a recessive model: noteworthy that relative excess risks rs223492 (MYOC), rs2302339 (INMT), due to interaction among these variants Professor Ma-Li Wong rs2228078 (GHRHR), rs1208 (NAT2), were highly significant providing evidence We are conducting work to develop rs701865 (PDE6C), and rs1043307 that non-linear interactions (epistasis) a framework for the prediction of (PSMD9). underlie genetic susceptibility to MDD. susceptibility to Major Depressive Advance Recursive Partition (tree-based) Moreover, the ARPA tree-based analysis Disorder (MDD), based on two Approach (ARPA) analyses performed to for the dbGaP data, depicted substantial hypotheses: assess MDD risk in clusters of variants reliability, replicating most of the genes showed that 8 nsSNPs had high order involved in the branching process found We genotyped 372 autosomal nsSNPs in our exploratory analyses (Fig 1). spanning 188 genes to investigate interactions in the control of tree growth relationships/gene-gene interactions; (Fig 1). We found that risk classification jcsmr.anu.edu.au/research/translational- these were defined by nsSNPs in tree analysis using 15 nsSNPs that medicine/pharmacogenomics pathways relevant to CNS function in had association with MDD diagnosis case-control samples to find recurrent identified multiple increased-MDD functional process themes in MDD. For genotype clusters and significant additive a first exploratory analysis step we used interactions in combinations of genotype a cohort sample of Mexican-Americans variants that were significantly associated cases and controls that consists of 321 with MDD. The combinations of genotype healthy controls and 278 MDD patients, variants that had relative excess risk collected at University of California, due to interaction were found in the Los Angeles (UCLA), funded by three following gene interactions: 1) HSD3B1 NIH institutes and centres. After quality and PSMD9, 2) PDLIM5 and BDNF, 3) control filters were applied and the PDLIM5 and MYOC, 4) BDNF and MYOC, Hardy-Weinberg Equilibrium was tested, and 5) USP36 and PSMB4 (Wong ML et al. Mol Psychiatry 2012;17:624-633). a total of 252 nsSNPs were available for Fig 1. Advance Recursive Partitioned Analysis (ARPA) using dbGaP analytical procedures. Fifteen nsSNPs Replication Phase with the dbGaP data reconstructed a tree resembling the tree generated during the exploratory phase with the Mexican-American MDD sample (left top showed significant genotypic association sample. To conduct independent corner inset). Most of the genes involved in the branching process; i.e., PDE6C, PSMD9, HSD3B1, BDNF, and PDLIM5 were replicated. For (P<0.05) with MDD diagnosis. replication in a different population, easier understanding, the exploratory tree is reproduced in the left top corner inset and genes in the two trees are colour matched (Wong ML et we used GWAS genotype information al. Mol Psychiatry 2012;17:624-633). from the major depression database of

Annual Review 2012 57 Diseases to which humans can be genetically predisposed

thousands of patients of different In 2013 The Translational Genomics Department of ethnicities. This body of collaborative Group moved into the Department of Translational work has provided the framework for Genome Biology. defining biomarkers, prognostic assays, Figure 1 and eventual personalized treatment Medicine options. The translational outcome of these findings cemented the basis for filing two world class patents: 1) “A Translational Genomics method for determining the susceptibility Group of a subject for developing ADHD”, (8003406), granted; and 2) “Methods Associate Professor Mauricio for detecting ADHD and predicting Arcos-Burgos severity and long-term outcome”, (HHS, The goal of our research is to identify Reference No. E-187-2011/0), granting genetic variations underpinning pending. Among more than 100 peer- inherited disorders as a tool of genetic- reviewed manuscripts published, we have epidemiological intervention. Our studies contributed 41 publications during the last led to the discovery of genes/loci 5 years (9 in 2012). predisposing to several mendelian and jcsmr.anu.edu.au/research/genome complex genetic disorders, i.e. attention biology/translational-genomics deficit/hyperactivity disorder (ADHD), Figure 1. Genotypic frequency distribution for pairs of SNPs contributing to interaction effects, and assessed by the Cochran-Mantel-Haenszel Alzheimer’s disease (AD), membranous test. Significant interaction effects involve markers in the LPHN3 gene and a region in 11q that harbors the NCAM1 and DRD2 genes. Epistatic nephropathy, non-syndromic cleft lip with effects are depicted by changes in color that represent significant differences in genotypic distribution among severe (cases) vs. not or without cleft palate (NS-CL/P), major severe (controls) individuals. In there, the genotypes for one marker are depressive disorder (MDD), Hartnup held fixed while genotypes on the other marker vary.I nattention: (A) Markers rs1947275 harbored in LPHN3 and rs17596017, in NCAM1, Disorder, Gray Platelet Syndrome, contribute to the severity of symptoms in this domain (M2=33.163, FDR-corrected P-value<0.001); (B) markers rs1947275 harbored in and East Syndrome. Our group also LPHN3 and rs12799083, in DRD2, produce a significant interacting effect contributing to the severity of symptoms (M2=28.456, FDR- participated, by contributing affected corrected P-value<0.005). H/I: (C) Markers rs35106420, in LPHN3, and rs620291, in NCAM1, produce an interacting effect contributing to families, to the discovery of IRF6 that the severity of symptoms (M2=20.497, FDR-corrected* P-value<0.05). ODD: (D) Markers rs995447, in LPHN3, and rs11214505, in NCAM1, when mutated cause Van der Woude interact to modify the severity of symptoms (M2=41.379, FDR-corrected and Popliteal Pterygium syndromes. P-value<0.0001); (E) rs734644, in LPHN3, and rs4938006 produce an epistatic effect contributing to the severity of symptoms (M2=26.795, We maintain a large international FDR-corrected P-value<0.01). A/D: (F) Markers rs1510920, in LPHN3, and rs4938006 localized closest to NCAM1 in an intragenic region collaboration, involving research of chromosome 11q, interact to modify the severity of symptoms (M2=41.379, FDR-corrected P-value<0.0001). groups from the Americas, Europe, and * FDR-Corrected P-values calculated on the basis of 567 independent Australia, providing a unique source tests, corresponding to the maximum number of SNP pairs for each of the four domains of the VAS-P questionnaire from which the severity of of genomic, clinical, environmental, symptoms was derived. Abbreviations as in Figure 1. and demographic information from

58 The John Curtin School of Medical Research Molecular pathways involved in the improvement of nonalcoholic fatty liver disease

lost body weight, higher leptin levels, of mitochondrial function, detoxification Department of improved glucose tolerance, and lower and antioxidative stress systems, which liver injury scores than sham-operated are critical in ameliorating oxidative stress Translational animals. in different liver diseases. Loss of GABP Medicine Transplantation of eWAT from Lep+/+ exacerbates animal models of NASH donors improved liver histology. Liver by causing mitochondrial dysfunction, steatosis was improved in eWAT- associated with the upregulation of cell Translational Medicine transplanted Lepob/ob mice; their liver death pathways via reactive oxygen samples showed primarily microvesicular species (ROS) and Ca2+ signaling. In Group steatosis, very few/no macrovesicules, no this setting, mitochondrial biogenesis visible injured hepatocytes (Figs. 1A and is increased as a compensatory Professor Julio Licinio 1C), and few Mallory bodies (Figs.1B and mechanism. By stimulating mitochondrial Non-alcoholic fatty liver disease (NAFLD), 1D). The liver injury score was significantly function and ameliorating oxidative the most common form of chronic liver lower in the transplanted animals as stress, GABP activation could be a dysfunction in developed countries. compared to the sham-operated group potential target for NASH treatment and While NAFLD could be considered a (P=0.0004). prevention. component of metabolic syndrome, the jcsmr.anu.edu.au/research/translational- liver involvement includes a spectrum Novel pathways involved in NAFLD medicine/translational-medicine ranging from simple steatosis (NAFLD) to Liver microarray analysis showed that non-alcoholic steatohepatitis (NASH) and novel pathways related to GA-binding cirrhosis. protein (GABP) transcription factor (TF) Approximately 23% of patients with targets, pheromone binding, and olfactory NAFLD progress to NASH, which is signaling were differentially expressed in histologically characterised by steatosis, transplanted mice. lobular inflammation, hepatocellular To our knowledge, this is the first study ballooning and fibrosis. Leptin therapy showing the differential expression leads to significant reductions in steatosis, of GABP TF targets associated with liver enzymes levels, and hepatocellular NABP improvement. GABP is the only injury in human lipodystrophy. obligate multimeric TF of the Ets family, To identify the effects and mechanisms intimately involved in critical cellular by which leptin influences the functions, including cell cycle control, Fig 1. Liver histology of the sham-operated (A and B) and transplanted (C and D) mice. (A and C) Hematoxylin and eosin, 200X; (B and D) Masson pathogenesis of NAFLD, we performed cytoprotection, T-cell development, Trichrome, 400X. Ma, macrovesicular steatosis; MB, Mallory bodies; MI, microvesicular steatosis; F, fibrosis; I, inflammation epididymal white adipose tissue (eWAT) protein synthesis, cellular metabolism, transplantation from congenic wild- embriogenesis, cellular differentiation, type mice into Lepob/ob recipient mice. apoptosis, and carcinogenesis. In the Transplanted mice had significantly liver, the GABP maybe a key regulator

Annual Review 2012 59 AUSTRALIAN PHENOMICS FACILITY

Funding of the APF was contributed to tissue samples and conducted over 2012 Highlights by the Federal Government schemes: 95,000 genotyping assays. (1) the National Collaborative Research At the start of 2012, the animal services Missense Mutation Project Infrastructure Strategy (NCRIS) and (2) the team was responsible for the care of over After trialling heterozygous single Education Investment Fund (EIF) Super 10,000 cages of rodents per week. Due nucleotide variant (SNV) detection in Science Program. to the completion of several large projects 2011 the APF successfully expanded the Co-tenants of the Hugh Ennor Building the cage number fell to approximately project providing the research community with the APF, the ANU Biosciences 6,800 in December. In addition to animal with thousands of new mutant mice for Research Facility (ABRF) provides care, the animal services technicians use in understanding disease biology and animal services, predominately rodent, performed tasks for researchers including providing models for the development to JCSMR and other ANU researchers blood collection, ear biopsy, injections, of new therapies. Whole exomes from and to the APF. The overlap in expertise, routine examination, tissue and organ 547 unique mice carrying ENU-induced services and resource requirements collection, phenotyping and post- mutations were sequenced using next of the APF and ABRF saw the natural mortems, freeing up researchers to spend generation technologies providing merger of the APF and ABRF under one more time conducting their experiments. 9,802 SNVs to the Australian research management structure in 2012. Dr Steve The animal services team also provide community. They are listed in a database Winslade was appointed CEO and Dr comprehensive training to all new users of managed by the APF and can be Suzanne Fowler was appointed Head of the facility. accessed at the following site: Animal Services. The APF manages the ANU node of databases.apf.edu.au/mutations/ This merger allows a more efficient the Australian Phenome Bank (APB). delivery of all of the services offered. The APB is a physical and electronic Australian Phenome Bank That is, as one entity, the new APF can repository for genetically modified mouse The APB successfully trialled and provide all services required for use of strains held in Australia as either live or implemented a new in vitro fertilisation rodents in research: from generation or cryopreserved material. Funding for the (IVF) technique for mouse sperm importation of new genetically modified APB was provided by the NCRIS and reanimation. 2-cell fertilisation rates using rodents, specific project management, EIF programs and allows researchers sperm thawed from the frozen bank colony maintenance and management, to search for strains that may be of use archive increased from 5 – 20% to 80%. genotyping and phenotyping services, for their research and also cryopreserve Researchers can have much greater strain archiving, preservation and their strains protecting this valuable confidence strains held in the repository distribution. resource against disaster and making can be efficiently re-animated from the The project management team oversaw them available for the future. During 2012, frozen stock. the running of 15 phenotype to genotype 453 strains were added to the database The Australian Phenomics Facility (APF) projects for clients external to the ANU. taking the total to 3229 strains. Of these is JCSMR’s national service organisation Genomics services team of the APF is 266 strains were cryopreserved taking the that creates mouse models of human responsible for genotyping the majority of total to 1702 strains in the frozen archive. disease and provides associated the animals housed at the APF. In 2012, www.apf.edu.au genomics and phenotypic services. the team prepared DNA from over 50,000 pb.apf.edu.au

60 The John Curtin School of Medical Research The ACRF Biomolecular Resource Facility and Genome Discovery Unit

The Australian Cancer Research The Genome Discovery Unit (GDU) by life science vendors including Foundation‚ Biomolecular Resource was established in 2011 to provide overviews of new equipment and Facility (BRF) provides consultancy and bioinformatics services for researchers technologies provided by the BRF and service provision in the areas of genetic employing HTS. This role includes technical advice for better experimental sequencing, microarrays, peptide custom analysis pipeline development, design and execution of experiments. synthesis, mass spectrometry, tetramer computation, and data storage. These seminars were well attended synthesis, chromatography and antibody Specifically, 2012 has seen establishment throughout the year. purification to ANU researchers, as well of ChipPy, a bioinformatic pipeline for The GDU facilitates interactions between as the wider scientific community. investigating structural Epigenetics Canberra bioinformaticians by organising Throughput DNA sequencing (HTS) using CHiP-Seq and a Genotype by the weekly Techniques in Computational constitutes a significant proportion of Sequencing pipeline for genotype Biology (TIC) seminar series and having the BRF workload and has continued analyses in non-model organisms. weekly drop-in sessions for biologists and to increase in demand over 2012, with In order to benefit ANU staff and students computational scientists. The role of these the facility acquiring a second Illumina and our colleagues at other Canberra is wide ranging, allowing researchers HiSeq2000. The BRF is also a service institutions, the BRF and GDU are to discuss and gain advice in areas node of Genomics Australia (part of involved in a number of workshops, such as experimental design through to Bioplatforms Australia). As part of this seminars and learning opportunities. bioinformatic code review. consortium, we have been sequencing These include BRF and GDU staff running brf.anu.edu.au genomes and biopsies from a large sequencing troubleshooting seminars, cohort of melanoma patients, with bioinformatics courses for ANU and datasets to be made available as a public CSIRO research staff and students, resource to scientists and clinicians (via contributing to undergraduate courses Genomics Australia). Other large-scale such as the ANU’s Bioinformatics and projects include sequencing mouse Functional Genomics course, Science in mutant strains to identify pathogenic the Workplace course, and The University single nucleotide polymorphisms with the of Canberra’s Molecular and Cellular Australian Phenomics Facility at ANU. Biology course. Additionally, the BRF hosts workshops and seminars presented

Annual Review 2012 61 62 The John Curtin School of Medical Research Staff and student Achievements

Graduates Prizes and Awards

Annual Review 2012 63 Graduates

PhD Charis En-Yi Teh Susanti Susanti Co-operative failure of Aire-mediated Angiogenesis modulating activity of Nod John Altin clonal deletion and Cblb-mediated Factor-derived compounds and histidine- On the regulation of T helper Type 2 (Th2) clonal anergy in the pathogenesis of rich glycoprotein responses autoimmunity

Julian Min Chiang Choy Anjum Zafar MNeurosience Adrenergic neuromodulation of transmitter Novel chromatin-associated role of Praveen Alexander release in rat neocortex protein kinase C family members Nurussyariah Hammado in regulating inducible genes and Jinghua Feng microRNAs during epithelial to Mudi Qin Genetic variants experiencing sexually mesenchymal transition antagonistic selection in humans Grad Cert Translational Ruwani Hewawasam MPhil Medicine Glutathione transferase-derived Ainy Khan Sooshin Choi compounds as potential therapeutic Adipose tissue transplantation improves agents metabolic, behavioural and histological parameters in leptin-deficient mice

64 The John Curtin School of Medical Research Prizes and Awards

Dr Rufika Abidin Professor Elizabeth Blackburn Most Engaging Oral Presentation: the Poster Prize: AusAid and Australia The Curtin Medal for Excellence in 24th Scientific Meeting of the International Awards Conference, Jakarta, Indonesia Medical Research Society of Hypertension New Investigator Symposium, , NSW Poster Prize: International symposium Ms S-Y Chan on Clinical Microbiology held jointly by Ms Fui Jiun Choong the Association of Indonesian Clinical Australasian Society for Immunology Postgraduate International Travel Award Young Investigator Award for Oral Microbiologists (PAMKI) and Novartis Presentation: ‘The role of heparanase Institute for Tropical Disease, Makassar, Bill and Melinda Gates Foundation Travel in the rejection of islet allografts’, 30th Indonesia Scholarship to attend the Keystone Annual Scientific Meeting, Transplantation Symposium: Immunological mechanisms Ms Nur Diana Anuar Society of Australia and New Zealand, of Vaccination, Ottawa, Canada Canberra, ACT The Ministry of Rural and Regional Development (Malaysia) Scholarship for Mr Daniel Chaston Dr Lucy Coupland PhD studies Best Oral Presentation: Australian Society The Dewar-Milne Prize in Immunology for Medical Research New Investigator Mr Hannes Bergmann Forum, Canberra, ACT Dr Anselm Enders First Prize: PhD Student Presentation: Best Laboratory Research Oral The Inaugural Gordon Ada New ACT and NSW Australasian Society of Presentation: Canberra Health Annual Investigator Award and Oration Immunology Branch Retreat, Bowral, Medical Research Meeting, Canberra, NSW Oral Presentation Award: 15th Biennial ACT Meeting, The European Society for Foundation for High Blood Pressure Immunodeficiencies, Florence, Italy Research Young Investigator Travel Award

Annual Review 2012 65 Professor Chris Goodnow Professor Ted Maddess Mr Roy Ramiscal The GlaxoSmithKline Award for Research The Australian National University Award Research Center for Allergy and Excellence for his pioneering work on for the Top PhD Supervisor Immunology (RCAI) International Summer autoimmune diseases Elected President and Public Officer of Scholar Dr Rebecca Haddock the Australian Vision Sciences Society Australasian Society for Immunology Travel Bursary to attend the 42nd Annual Foundation for High Blood Pressure Ms Susan Morton Scientific Meeting of the Australasian Research Travel Award to attend the 24th Foundation for High Blood Pressure Society for Immunology, Melbourne, VIC Scientific Meeting of the International Research Travel Award to attend the 24th Society of Hypertension, Sydney, NSW Scientific Meeting of the International Dr Katrina Randall Ms Amy D Hanna Society of Hypertension, Sydney, NSW The Federation of Clinical Immunology Poster presentation award: Viewers’ Societies (FOCIS) Travel Award to attend Best Student Oral Presentation Award, FOCIS 2012, Vancouver, Canada Gage Muscle Conference, Canberra, ACT choice poster, Australian Society of Medical Research New Investigator Ms Jennifer Robertson Professor Caryl Hill Forum, Canberra, ACT Best oral presentation, Kioloa Visiting Professor, Department of Dr Maxim Nekrasov Neuroscience Colloquium, ANU Kioloa Physiology and Pharmacology, University Campus, Kioloa, NSW of Southern Denmark ANU Travel Grant to attend Epigenetics & Chromatin, Cold Spring Harbor Dr Zahra Sabouri Ms Carly Hynes Laboratories, Cold Spring Harbor, NY, US Australasian Society for Immunology Heart Foundation Travel Grant Award Professor Christopher Parish International Travel Bursary to attend to attend the Keystone Symposium The Australasian Society for Immunology Keystone Symposia: B Cell Development ‘Noncoding RNAs in Development and and Function, Keystone, CO, US Cancer’ Keystone, CO, US Honorary Life Membership: Awarded in recognition of his enormous contribution Keystone Symposia Future of Science The Australian Society for Biochemistry to the Society and to Immunology Fund scholarship for Keystone Symposia: and Molecular Biology Student Travel Research in Australia B Cell Development and Function, Bursary to attend ComBio, Adelaide, SA Keystone, CO, US Dr Ian Parish Travel Bursary Award to attend the ARC ANU Vice-Chancellor’s HDR Travel Grant Centre of Excellence in Bioinformatics New Investigator Presentation Award: to attend the Keystone Symposia: B Cell Winter School in Mathematics and ACT and NSW Australasian Society of Development and Function, Keystone, Computational Biology, University of Immunology Branch Retreat, Bowral, CO, US Queensland, St Lucia, QLD NSW Australasian Society for Immunology Ms Sau Kuen Lee Ms Eva Pillai Travel Bursary to attend the 42nd Annual Keystone Symposia Future of Science Master of Neuroscience (Research) Scientific Meeting of the Australasian Fund Scholarship to attend Keystone Scholarship, The John Curtin School of Society for Immunology, Melbourne, VIC Symposia meeting on Mutations, Medical Research, ANU Third Prize: Oral Presentation: ACT and Malignancy and Memory – Antibodies Summer Research Fellowship, The NSW Australasian Society of Immunology and Immunity, Boston, MA, US Centre for Healthy Ageing, University of Branch Retreat, Bowral, NSW Immunology Frontier Research Center Copenhagen, Denmark RIKEN/RCAI International Summer (IFReC) Scholarship to attend Winter Program Scholarship, Yokohama, Japan School on Advanced Immunology, Osaka Dr Jason Potas University and Singapore Immunology Bootes Foundation Award: Promoting Ms Tennille Sibbritt Network (SIgN), Kobe, Japan nervous system regeneration with 3D Student Poster Prize: 33rd Annual Lorne nanofibre scaffolds Genome Conference, Lorne, VIC Ms Jasmine Li ANU Vice-Chancellor’s Travel Grant University of Canberra Best Poster Oral Presentation Runner-up: Australian Award to attend The 32rd Annual Meeting Presentation: Australian Society for Society for Medical Research New of the Australasian Neuroscience Society, Medical Research New Investigator Investigator Forum, Canberra, ACT Gold Coast, QLD Forum, Canberra, ACT

Mr Kerry McAndrew Mr Alvin Pratama Travel Bursary Award to attend the ARC Centre of Excellence in Bioinformatics 40 years service at The Australian Australasian Society for Immunology National University Winter School in Mathematics and Travel Bursary to attend the 42nd Annual Computational Biology, University of Scientific Meeting of the Australasian Queensland, St Lucia, QLD Society for Immunology, Melbourne, VIC The Australian Society for Biochemistry and Molecular Biology Student Travel Bursary to attend ComBio, Addelaide, SA

66 The John Curtin School of Medical Research Mr Manu Singh Mr Jorge Vélez Mr Mehmet Yabas Second Prize: PhD Student Presentation: ANU Eccles Scholarship in Medical Immunology Frontier Research Center ACT and NSW Australasian Society of Sciences, The Australian National (IFReC) Scholarship to attend Winter Immunology Branch Retreat, Bowral, NSW University, Canberra, ACT School 2012 on Advanced Immunology, Osaka University and Singapore Dr Zan-Min Song Fenner Merit Scholarship, The Australian National University, Canberra, ACT Immunology Network (SIgN), Kobe, Japan Bootes Foundation Award: Stem cell ANU Higher Degree Research (HDR) Award from The American Association transplantation in treating cerebellum cell for the Advancement of Science (AAAS)/ loss in Hirschsprung’s disease Merit Scholarship, The Australian National University, Canberra, ACT Science Program for Excellence in Science Professor Greg Stuart Professor Carola Vinuesa Elected Fellow of the Australian Academy European Federation of Immunological of Science for “seminal contributions The Official Cross of Isabel la Católica Societies (EFIS) Travel Grant to attend the to understanding how information is – a civil order granted in recognition of 3rd European Congress of Immunology, processed by individual nerve cells within services that benefit Spain , UK the brain” The Australian National University Vice- Dr Harpreet Vohra Chancellor’s Higher Degree Research Thomson Reuters Australia Citation Australian Government Endeavour Award for the highest cited Neuroscientist Travel Grant to attend the 3rd European Executive Award to undertake study, Congress of Immunology, Glasgow, UK in Australia based on research volume research and professional development in and impact over the ten-year period from the laboratory of Professor Gary Nolan at Dr Andrew Z Ziolkowski 2002 to 2011 , Palo Alto, CA, US Best Poster Award: ‘Preventing beta cell demise in Db/Db mice with heparan Dr Rebecca Sweet Dr Mr Danushka K Wijesundara sulfate mimetics’, 5th Australian Islet American Australian Association Sir Keith Australian Society for HIV Medicine Murdoch Fellowship Study Group (AISG) Meeting, Melbourne, (ASHM) Scholarship to attend the 24th VIC Human Frontier Science Program Long Annual Conference of the Australasian Term Fellowship Society for HIV/AIDS Medicine, Melbourne, VIC Ms Clara Tang ANU Vice-Chancellor’s Higher Degree The University Medal in Medical Science Research Travel Grant

Dr Charis Teh Dr Zuopeng Wu Becton Dickinson Science Australian Diabetes Society Travel Grant Communication Prize: 42nd Annual to present: ‘Heparanase is indispensable Scientific Meeting of the Australasian for autoreactive T cell infiltration into islets Society for Immunology, Melbourne, VIC in Type 1 diabetes”, Annual Scientific Meeting of the Australian Diabetes Professor David Tremethick Society and the Australian Diabetes Inaugural ANU College of Medicine Educators Association, Gold Coast, QLD Biology and Environment Prize for Outstanding Research Achievement

Dr Krisztina Valter Citation for Outstanding Contributions to Student Learning from the Office for Learning and Teaching (OLT) for ‘inspirational teaching through the development of authentic, innovative, interactive and engaging teaching approaches, curricula and resources in medical sciences’ ANU Vice-Chancellor’s Award for Excellence in Education Outstanding Contribution to Student Learning

Annual Review 2012 67 68 The John Curtin School of Medical Research Visitors and Collaborations

Research Collaborations and Visitors to the School Staff and students at JCSMR Continue to enjoy close collaborative ties with other researchers at The Australian National University. In addition, they collaborate with colleagues locally, regionally, nationally and internationally, and these are listed here. In 2012, we welcomed visitors into the School to present research findings, or to spend time undertaking research projects with our staff and students.

Annual Review 2012 69 Visitors

Professor Leonard Arnolda Dr Ben Corry Dr Daniel Gray Cardiology, The Canberra Hospital, Transport Proteins and Computational Molecular Genetics of Cancer Division, Canberra, ACT and ANU Medical School, Biophysics Lab, Research School of The Walter and Eliza Hall Institute, The Australian National University, Biology, The Australian National University, Melbourne, VIC Canberra, ACT Canberra, ACT Professor Jörg Heierhorst Professor Richard Banati Associate Professor Andrew Molecular Genetics Unit, Department Faculty of Health Sciences, The University Coward of Medicine, St Vincent’s Hospital, The of Sydney, Sydney, NSW ANU College of Engineering and , Melbourne, VIC Computer Science, The Australian Associate Professor Nigel Barnett National University, Canberra, ACT Associate Professor Luke Queensland Eye Institute, South , Henderson QLD Professor Sheila Crewther Anatomy & Histology, School of Medical Department of Psychology, School Sciences, , Sydney, Professor Traude Beilharz of Psychological Science, Faculty of NSW Department of Biochemistry and Science, Technology and Engineering, La Molecular Biology, School of Medical Trobe University, Melbourne, VIC Professor Mathias Hentze Sciences, , Melbourne, EMBL (European Molecular Biology VIC Professor Jens-Karl Eilers Laboratory), Heidelberg, Germany Faculty of Medicine, Carl Ludwig Institute Dr Peter Boag of Physiology, University of Leipzig, Associate Professor Livia Hool Developmental and RNA Biology Leipzig, Germany School of Anatomy, Physiology and Laboratory, Department of Biochemistry Human Biology, The University of Western and Molecular Biology, School of Medical Professor Geoff Farrell Australia, , WA Sciences, Monash University, Melbourne, Gastroenterology and Hepatology Unit, VIC The Canberra Hospital, Canberra, ACT Professor David James and ANU Medical School, The Australian Diabetes & Obesity Research Program, Professor Charles Bond National University, Canberra, ACT Garvan Institute of Medical Research, Faculty of Life and Physical Sciences, The Sydney, NSW University of Western Australia, Perth, WA Dr Archa Fox Western Australia Institute for Medical Professor Anthony Kelleher Associate Professor Robert Brink Research (WAIMR) and University of The Kirby Institute, St Vincent’s Centre for Immunology Program, Garvan Institute of Western Australia, Perth, WA Applied Medical Research, Sydney, NSW Medical Research, Sydney, NSW Professor Robert French Associate Professor Maija Professor Stefan Broer Department of Physiology and Kohonen-Corish Division of Biomedical Science and Pharmacology, University of Calgary, Cancer Research Program, Garvan Biochemistry, Research School of Biology, Calgary, Alberta, Canada Institute of Medical Research, Sydney, The Australian National University, NSW Canberra, ACT Professor Katharina Gaus Australian Centre for NanoMedicine, Professor Graham Lamb Professor Susan Clark Faculty of Medicine (Centre for Vascular Faculty of Science, Technology and Epigenetics Research Group, Cancer Research), Lowy Cancer Research Engineering, School of Life Sciences, Research Program, Garvan Institute of Centre, The University of New South Department of Zoology, La Trobe Medical Research, Sydney, NSW Wales, Sydney, NSW University, Melbourne, VIC

Dr Nicole Cloonan Professor Georges ER Grau Dr Bradley Launikonis Queensland Centre for Medical Department of Pathology, Sydney Medical School of Biomedical Sciences, The Genomics, Institute for Molecular School, The University of Sydney, Sydney, University of Queensland, Brisbane, QLD Bioscience, The University of Queensland, NSW Brisbane, QLD Professor Peter Leedman Professor Robert Graham Dr Ian Cockburn Laboratory for Cancer Medicine, Western Molecular Cardiology and Biophysics Australian Institute for Medical Research Johns Hopkins Malaria Research Institute, Division, The Victor Chang Cardiac (WAIMR) and University of Western Bloomberg School of Public Health, Research Institute, Sydney, NSW Australia, Perth, WA Baltimore, MD, US

70 The John Curtin School of Medical Research Professor Joel McKay Assistant Professor Jack Waters Biochemistry, School of Molecular Department of Physiology, The Feinberg Bioscience, University of Sydney, Sydney, School of Medicine, North Western NSW University, Chicago, IL, US

Dr Edward S Mocarski Jr Associate Professor Dagmar Emory Vaccine Center, Emory University Wilhelm School of Medicine, Atlanta, GA, US Non-coding RNA and Sex Determination Laboratory, Department of Anatomy Dr Florian Obermayr and Developmental Biology, Faculty of Department of Anatomy and Medicine, Nursing & Health Sciences, Neuroscience, University of Melbourne, Monash University, Melbourne, VIC Melbourne, VIC and University of Tübingen, Tübingen, Germany Professor Steve Wilton Molecular Genetic Therapies Group, Professor Davis Sansom Centre for Neuromuscular and College of Medical and Dental Sciences, Neurological Disorders, University of University of Birmingham, Edgbaston, Western Australia, Crawley, WA and Birmingham, UK The Australian Neuromuscular Research Institute, Nedlands, WA Dr Leoš Shivaya Valášek Laboratory of Regulation of Gene Dr Colby Zaph Expression, Institute of Microbiology AS The Biomedical Research Centre, CR, Prague, University of British Columbia, Vancouver, BC, Canada Associate Professor Chris Sobey Department of Pharmacology, Monash University, Melbourne, VIC

Dr John Stambas CSIRO Australian Animal Health Laboratory, Geelong, VIC

Dr Daniela Stock Structural and Computational Biology Division, The Victor Chang Cardiac Research Institute, Sydney, NSW

Dr Alex Swarbrick Tumour Progression Group, Cancer Program, Garvan Institute of Medical Research, Sydney, NSW

Dr Christian Thoma Department of Medicine II, Freiburg University Medical Centre, Freiburg, Germany

Associate Professor Yuki Tomari Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan

Dr Lucy Walker College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK

Annual Review 2012 71 Collaborations

Ms Nur Diana Anuar Cherbuin Centre for Research on Ageing Associate Professor John M Health and Wellbeing, The Australian An investigation on the role of histone National University, Canberra, ACT Bekkers variant H2A.Lap1 in the central nervous Excitability and hyperexcitability of neural systems (CNS) Associate Professor circuits in the rodent piriform cortex Professor Peter Koopman Institute for Mauricio Arcos-Burgos, Professor S Nelson Brandeis Molecular Bioscience, The University of University, Waltham, MA, US Professor Queensland, Brisbane, QLD Professor Christopher G Augustine National University of C Goodnow and Dr Dan Singapore, Singapore, Korea Institute of Dr Stuart Archer Andrews Science and Technology, Seoul, South Korea, and Duke University, Durham, NC, Translational regulation and alternative Translational genomics of autoimmune US splicing in neuronal stem cells disorders Neural circuits for odour-processing in the Dr L Vardy Institute of Medical Biology, Dr Juan Manuel Anaya University of rodent piriform cortex ‘in vivo’ A*STAR, Singapore Rosario, Bogota, Colombia Professor M Larkum Charité-Humboldt Post-transcritional control of gene University, Neuroscience Research expression in inflammation Dr Nicole A Beard Center, Berlin, Germany PD Dr D Ostareck University Hospital Persistent firing in cortical interneurons: Aachen, RWTH Aachen University Regulation of calcium release channels (RyR2) in cardiac disease Mechanisms and potential anticonvulsant Aachen, Germany role Dr D Laver Hunter Medical Research Dr M McDonnell Institute of Associate Professor Institute, University of Newcastle, Newcastle, NSW Telecommunications Research, University Mauricio Arcos-Burgos of South Australia, Adelaide, SA Actions of triadin on excitation-contraction Translational genomics of Attention coupling Test of novel anticonvulsants for clinical applications Deficit/Hyperactivity Disorder Professor RT Dirksen Department of Professor FX Castellanos New Pharmacology and Physiology, University Dr J Daniel Children’s Medical Research York University, New York, NY, US Dr of Rochester Medical Centre, Rochester, Institute, University of Sydney, Sydney, M Ribases University of Barcelona, NY, US NSW Barcelona, Spain Dr M Muenke, National Changes in calsequestrin, triadin and Human Genome Research Institute, junctin in heart failure Dr Andrew Bell National Institutes of Health, Bethesda, MD, US Professor S Gyorke Department of Studies of otoacoustic emissions from the Physiology and Cell Biology, Davis Heart human cochlea Translational genomics of Alzheimer’s and Lung Research Institute, The Ohio disease Dr W Jedrzejczak Institute of Physiology State University, Columbus, OH, US and Pathology of Hearing, Warsaw, Dr F Lopera University of Antioquia, Calsequestrin as a luminal calcium sensor Poland Medellín, Antioquia, Colombia Dr KS in skeletal muscle Kosik University of California, Santa Barbara, CA, US Professor M Varsanyi Institut für Dr Edward M Bertram Physiologische Chemie, Ruhr Universität, Translational genomics of non-syndromic Bochum, Germany Role of TNF family member LIGHT in EAE cleft lip/cleft palate Junctin expression in fast and slow twitch Dr M Staykova, Dr D Linares and S Dr M Carmago University of Antioquia, Fordham Neurosciences Research Unit, Medellín, Antioquia, Colombia Dr L Dr F Protasi Interuniversitary Institute of The Canberra Hospital, Canberra, ACT Moreno and Dr A Lidral Iowa State Myology, Department of Neuroscience Dr K Pfeffer and Dr S Scheu Institute University, Ames, IA, US and Imaging, Università degli Studi G of Medical Microbiology and Hospital d’Annunzio, Chieti, Italy Hygiene, University of Dusseldorf, Associate Professor CSQ expression in cardiac and skeletal Dusseldorf, Germany muscle Mauricio Arcos-Burgos and Dr N Bal Davis Heart and Lung Research Dr Edward M Bertram and Professor Simon Easteal Institute, The Ohio State University, Professor Chris C Goodnow Translational genomics of Attention Columbus, OH, US Deficit/Hyperactivity Disorder China-Australia Centre for Phenomics Research Associate Professor M Bellgrove School of Psychology, The University of Professor H Tang Centre for Infection Queensland, Brisbane, QLD Dr Nicolas and Immunity, Chinese Academy of

72 The John Curtin School of Medical Research Sciences, Institute of Biophysics, China Function of Zeta and Omega class GSTs Design and development of M2 influenza Professor Y Zhang BGI, Shenzhen, Professor MW Anders Department of A inhibitors China Associate Professor M Beard Pharmacology and Physiology, University Professor W Hu Guangzhou Institute School of Molecular and Biomedical of Rochester Medical Centre, Rochester, of Biomedicine and Health, Chinese Sciences, The University of Adelaide, NY, US Academy of Sciences, Science Park, Adelaide, SA Professor J Xu School of Guangzhou, China Pathology and Laboratory Medicine, The Structure of γ-glutamyl cyclotransferase University of Western Australia, Perth, WA Associate Professor A Oakley School Mr Aaron Chuah Australian Centre for Vertebrate Mutation of Chemistry, University of Wollongong, Detection Wollongong, NSW Genotyping by Sequencing Professor D Hilton Molecular Medicine Microbial Omega-like GSTs Dr J Borevitz Research School of Division, The Walter and Eliza Hall Institute Professor L Xun School of Molecular Biology, The Australian National University, of Medical Research, Melbourne, VIC Biosciences, Washington State University, Canberra, ACT Pullman, WA, US Transcriptome sequencing of two Dr Anneke C Blackburn The expression of γ-glutamyl phenotypic mosaic Eucalyptus trees cyclotransferase in human cancer Mouse mammary tumour susceptibility Dr C Kuleim Research School of Biology, loci Professor Y Eishi Department of Human The Australian National University, Pathology, Tokyo Medical and Dental Canberra, ACT Professor DJ Jerry Veterinary University, Tokyo, Japan and Animal Sciences, University of Transcriptome sequencing and differential Massachusetts, Amherst, MA, US New cardiac ryanodine receptor inhibitors expression analysis of four Arabidopsis for the treatment of heart failure cultivars Targeting breast cancer with dichloroacetate and the mitochondrial Professor L Arnolda The Canberra Dr I Searle Research School of Biology, toxin PENAO Hospital, Canberra, ACT and ANU The Australian National University, Medical School, The Australian National Canberra, ACT Professor PJ Hogg and Dr PJ Dilda University, Canberra ACT Lowy Cancer Research Centre, University of , Sydney, NSW Dr Adam Cook Targeting of Two Aspects of Metabolism Dr Marco G Casarotto Investigating histone dynamics and (TOTAM) for Cancer Therapy Molecular recognition of the ryanodine metabolism Professor JE Dahlstrom Anatomical receptor Dr G Almouzni UMR218 CNRS / Institut Pathology and Associate Professor Dr M Samso Department of Physiology Curie – Section de Recherche, Paris, D Yip Medical Oncology, The Canberra and Biophysics, VCU School of Medicine, France Hospital, Canberra, ACT and ANU Richmond, VA, US Medical School, The Australian National Determination of glutathione transferase University, Canberra, ACT Associate Professor structures Human breast cancer modifier gene Matthew Cook Professor M Parker Biota Structural discovery through the Kathleen Australian and New Zealand Antibody Biology Laboratory, St Vincent’s Institute, Cuningham Foundation Consortium for deficiency allele (ANZADA) study Melbourne, VIC Research into Familial Breast Cancer Dr S Adelstein and Dr R Garsia (kConFab) Interactions between the alpha and beta Department of Immunology, Royal Prince subunits of the dihydropyridine receptor Dr A Spurdle The Molecular Cancer Alfred Hospital, Camperdown, NSW Dr Epidemiology Laboratory, Queensland Associate Professor A Oakley School T DeMalmanche HAPS Immunology, Institute of Medical Research, Brisbane, of Chemistry, University of Wollongong, Newcastle, NSW Dr P Hissaria Royal QLD Dr G Chenevix-Trench Cancer Wollongong, NSW Adelaide Hospital, Adelaide, SA Dr Genetics Laboratory, Queensland Institute Structure and function of lysine M French School of Pathology and of Medical Research, Brisbane, QLD demethylase enzymes Laboratory Medicine, The University of Western Australia, Perth, WA Dr S Choo Dr S Rao Department of Applied Professor Philip G Board Royal Melbourne Children’s Hospital, Science, University of Canberra, Melbourne, VIC Professor D Campbell Determination of glutathione transferase Canberra, ACT and Dr S Mehr The Children’s Hospital structures Effects of drugs that block Vpu ion at Westmead, Westmead, NSW Dr S Professor M Parker Biota Structural channels Riminton Department of Immunology, Concord Repatriation General Hospital, Biology Laboratory, St Vincent’s Institute, Professor W Fischer School of Concord, NSW Dr D Fulcher Melbourne, VIC Biomedical Science and Engineering, Department of Immunopathology, National Yang-Ming University, Taipei, The Children’s Hospital at Westmead, Taiwan Westmead, NSW

Annual Review 2012 73 Genotypes and phenotypes of human Dr Lucy Coupland Professor Angela Dulhunty primary non-congenital antibody deficiency Mechanisms and novel treatment Various aspects of ryanodine receptor avenues for auto-immune cytopenias physiology Dr D Fulcher Department of Immunopathology, The Children’s Hospital Dr J D’Rozario and Dr P Crispin Dr D Laver Hunter Medical Research at Westmead, Westmead, NSW Haematology Department, The Canberra Institute, University of Newcastle, Hospital, Canberra, ACT Newcastle, NSW A randomised trial to assess antibody and cellular responses to hepatitis B vaccine Characterisation of erythrocyte Contribution of splicing defects in in patients with chronic kidney disease abnormalities in hemoxygenase-1 ryanodine receptors to myotonic (VaccineCKD) deficient mice dystrophy Dr K Karp The Canberra Hospital, Professor R Stocker, Dr R Winter and Professor RT Dirksen and Dr L Wei Canberra, ACT Dr S Fraser Sydney Medical School, The Department of Pharmacology and University of Sydney, Sydney, NSW Physiology, University of Rochester CCR5 expression on B cells in immune Medical Centre, Rochester, NY, US deficiency Dr Stephen Daley Actions of triadin on excitation-contraction Professor H Korner University of coupling Tasmania, Hobart, TAS Destabilisation of the translocase of the outer mitochondrial membrane by a novel Professor RT Dirksen and Dr L Wei Assessing the impact of solar ultraviolet ENU-induced variant of Tomm40 Department of Pharmacology and radiation on the immune response to Physiology, University of Rochester primary vaccination: the AusUVI Study Professor M Ryan Department of Medical Centre, Rochester, NY, US Biochemistry, La Trobe University, Associate Professor R Lucas, Dr S Melbourne, VIC CPVT mutations in the cardiac RyR Harrison, Professor A McMichael, Associate Professor K Dear and Dr Pulmonary hypertension caused by a Professor M Varsanyi Institut für A Swaminathan National Centre for novel ENU-induced variant of Tomm40 Physiologische Chemie, Ruhr Universität, Bochum, Germany Epidemiology and Population Health, The Professor L Arnolda The Canberra Australian National University, Canberra, Hospital, Canberra, ACT and ANU Structure of ion channel domain peptides ACT Medical School, The Australian National Professor N Ikemoto Boston STAT3 and hyper IgE syndrome University, Canberra, ACT Biomedical Research Institute, Boston, Dr S Tangye Garvan Institute of Medical MA, US Research, Sydney, NSW Dr Vincent Daria Changes in calsequestrin, triadin and junctin in heart failure Biological measurement beyond the Associate Professor quantum limit Professor S Gyorke Department of Physiology and Cell Biology, Davis Heart Matthew C Cook, Professor Professor W Bowen Physics, Faculty and Lung Research Institute, The Ohio of Science, University of Queensland, St Chris C Goodnow and State University, Columbus, OH, US Lucia, QLD Professor H Bachor The Professor Carola G Vinuesa Australian National University, Canberra, FRET analysis of DHPR beta subunit Australian point mutation in systemic ACT binding to the skeletal RyR lupus erythematosus (APOSLE) study Optically controlled containers for Professor B Fruen Biochemistry, Professor P Gatenby The Canberra experiments in soft matter Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, Hospital, Canberra, ACT Dr S Adelstein Professor E Sevick Research School US and Dr R Garsia Department of of Chemistry, The Australian National Immunology, Royal Prince Alfred Hospital, University, Canberra, ACT Accessory protein binding sites on the 3D Camperdown, NSW Dr D Mallon profile of RyR1 and RyR2 Fremantle Hospital, Fremantle, WA Dr Professor T Wagenknecht and Dr Z S Alexander The Children’s Hospital Dr Guowen Duan Liu Wadsworth Center, New York State at Westmead, Westmead, NSW Dr S miRNA function and turnaround Department of Health, Albany, NY, US Riminton Department of Immunology, Concord Repatriation General Hospital, Dr M Chong Genomics and Immunology The 3D location of the SPRY2 domain in Concord, NSW Dr D Fulcher Laboratory, St Vincent’s Institute of RyR1 Medical Research, Melbourne, VIC Dr J Department of Immunopathology, Dr M Samso Brigham and Womens Babon Structural Biology, The Walter and The Children’s Hospital at Westmead, Hospital, Harvard Medical School, Eliza Hall Institute of Medical Research, Westmead, NSW Boston, MA, US Melbourne, VIC

74 The John Curtin School of Medical Research Single channel activity of RyRs from ACT Professor A Mackinnon ORYGEN Analysis of B cell development in humans normal human and DM1 muscle Youth Health and The University of and mice with mutations in Card11 Professor K North and Dr N Clarke Melbourne, Melbourne, VIC Professor Professor Kl Warnatz Centre for Discipline of Paediatrics and Child Health, P Sachdev School of Psychiatry, The Chronic Immunodeficiency, University The Children’s Hospital at Westmead, The University of New South Wales, Sydney, Hospital, Freiburg, Germany NSW University of Sydney, Sydney, NSW Genetic analysis of humans with New cardiac ryanodine receptor inhibitors Gene expression changes in response to immunodeficiency of unknown aetiology training for the treatment of heart failure Professor H Eibel and Professor S Ehl Professor L Arnolda The Canberra Dr C Gore Australian Institute of Sport, Centre for Chronic Immunodeficiency, Hospital Canberra, ACT and ANU Medical Canberra, ACT University Hospital, Freiburg, Germany School, The Australian National University, Gene expression changes in response to Identification of ENU-induced point Canberra, ACT blood doping mutations in mouse strains with Mutations in CLIC-2 proteins leading to Dr C Gore Australian Institute of Sport, immunodeficiency ryanodine receptor channelopathy heart Canberra, ACT Dr K Bull and Professor R Cornall failure and intellectual deficit The genetics of economic behaviour Oxford University, Oxford, UK Professor C Schwartz and Dr E Axelov Professor N Martin Queensland Institute JC Self Research Institute of Human of Medical Research, Brisbane, QLD Dr Craig Freeman Genetics, Greenwood Genetic Center, Greenwood, SC, US and Department The genetics of economic behaviour Heparan sulfate mimetics as potential of Physics, Computational Biophysics Dr P Hatemi Pennsylvania State therapeutics to reduce neutrophilic and Bioinformatics, Clemson University, University, University Park, PA, US inflammation in chronic obstructive Clemson, SC, US pulmonary disease Genotyping tandem-repeat variation by Actions of φ-LITX-Lw1a on ryanodine sequencing Dr DKY Shum Department of receptors Biochemistry, The University of Hong Dr A Olsheck Murdoch Children’s Kong, Dr J Smith and Professor P Alewood Research Institute, Melbourne, VIC Institute for Molecular Biosciences, The Role of heparanase in diabetic retinopathy Estimating the fine-scale genetic structure University of Queensland, St Lucia, QLD of human populations Dr J Hu State Key Laboratory of The roles of calsequestrin in fast and slow Ophthalmology, Zhongshan Ophthalmic Dr S Leslie Murdoch Children’s Research twitch skeletal muscle Center of Sun Yat-Sen University, Institute, Melbourne, VIC Professor F Protasi CeSI, Center for GuangZhou, China Appropriate ethical framework for genetic Research on Ageing, Department of Heparan sulfate mimetics and malaria studies of Indigenous Australians Neuroscience and Imaging, Università Professor JG Beeson Centre for Gabriele d’Annunzio, Chieti, Italy Dr E Kowal University of Melbourne, Immunology, Burnet Institute, Melbourne, Melbourne, VIC Effects of aging on the distribution of VIC excitation-contraction coupling proteins in Molecular dynamics simulations of human skeletal muscle Dr Anselm Enders heparanase and chemokine interactions Professor P Smith Trauma and Analysis of the putative phospholipid with heparan sulfate mimetics Orthopaedic Research Unit, The Canberra transporter ATP11C Associate Professor RL Mancera Hospital, Canberra, ACT Professor S Broer Research School of School of Biomedical Sciences, Curtin Effects of the beta subunit of the DHPR Biology, The Australian National University, University, Perth, WA on excitation-contraction coupling Canberra, ACT Heparan sulfate mimetics and respiratory Professor M Schneider Biochemistry Analysis of liver tumor development in syncytial virus infection and Molecular Biology, University of ATP11C deficient mice Associate Professor L Simson Maryland School of Medicine, Baltimore, Professor N Teoh The Canberra Faculty of Applied Science, University of MD, US Hospital, Canberra, ACT Canberra, Canberra, ACT Analysis of MHC invariant chain Sulfated oligosaccharides as potential Professor S Easteal processing and development of dendritic therapeutics in Alzheimer’s Disease PATH Through Life Study cells in SPPL2A deficient mice Professor DH Small Menzies Research Associate Professor K Anstey, Professor J Villadangos Department of Institute, University of Tasmania, Hobart, Professor H Christensen, Dr P Microbiology and Immunology, University TAS Butterworth and Dr N Cherbuin of Melbourne, Melbourne, VIC Centre for Mental Health Research, The Australian National University, Canberra,

Annual Review 2012 75 Heparanase as a potential biomarker in and Professor B Beutler The Scripps Professor Chris C Goodnow rheumatoid arthritis Research Institute, La Jolla, CA, US Dr A and Dr Carola G Vinuesa Professor PN Smith, Professor PA Aderem and Dr I Shmulevic Institute for Gatenby and Dr RW Li Trauma and Systems Biology, Seattle, WA, US Dr G Immunity and Infection Genomics Orthopaedic Research Unit, The Canberra Nolan Department of Microbiology and Consortium Immunology, Stanford University, Palo Hospital, Canberra, ACT Dr R Cornall Nuffield Department of Alto, CA, US Heparanase activity in human primary Clinical Medicine, Oxford University, osteoblasts Oxford, UK Professor J Bell The Professor Chris C Goodnow, Weatherall Institute of Molecular Professor PN Smith, Professor PA Dr Edward M Bertram, Dr Medicine, Oxford University, Oxford, Gatenby and Dr RW Li Trauma and UK Professor W Britton and Dr B Orthopaedic Research Unit, The Canberra Katrina Randall and Dr Saunders Centenary Institute of Cancer Hospital, Canberra, ACT Stephen Daley Medicine and Cell Biology, The University Histone inhibition of Sydney, Sydney, NSW Professor M Identifying genes for immunity and Lathrop National Centre for Genotyping, Professor RW Stephens Browitt tolerance Evry, France Nanoparticle Lab, Research School of Dr J Cyster, Professor L Lanier Physics and Engineering, The Australian and Professor A Weiss University of National University, Canberra, ACT Professor Chris C Goodnow, California, San Francisco, CA, US Perlecan and heparanase modulation Professor Carola G Vinuesa of fibroblast growth factor (FGF-18) and Associate Professor signalling Professor Chris C Goodnow Matthew Cook Professor J Whitelock Graduate School and Associate Professor of Biomedical Engineering, University of Matthew C Cook Molecular and cellular studies of the New South Wales, Sydney, NSW adaptive immune response in health and Ndfip1 aborts tolerogen-induced disease Heparan sulfate mimetics and division and differentiation of CD4+ T myeloperoxidase cells to prevent Th2 inflammation and Professor C Mackay and Professor F Mackay-Fisson Monash University, Dr SR Thomas Centre for Vascular autoimmunity Clayton, VIC Professor J Sprent, Research, School of Medical Sciences, Professor S Tan and Dr J Howitt Florey Emeritus Professor A Basten, Dr University of New South Wales, Sydney, Neurosciences Institute, The University of S Tangye and Dr R Brink Garvan NSW Melbourne, Melbourne, VIC Dr S Kumar Institute of Medical Research, Sydney, Centre for Cancer Biology, SA Pathology, NSW Professor B Fazekas Centenary Professor Chris C Goodnow Adelaide, SA Dr L Wu Department of Institute of Cancer Medicine and Cell Immunology, Genentech, San Francisco, and Dr Edward M Bertram Biology, The University of Sydney, Sydney, CA, US NSW Mutations affecting male fertility Professor Jill E Gready Dr M O’Bryan and Professor D Professor Chris C Goodnow DeKretser Monash Institute of and Dr Anselm Enders Development of ANU technology for the Reproduction and Research, Melbourne, design of variant Rubisco proteins with VIC Analysis of NKT development and improved catalytic activity function in mouse strains with ENU Role of hnRNPLL in generating protective Professor JE Evans Research School of induced point mutations immunity to mycobacteria tuberculosis Biology, The Australian National University, Professor D Godfrey Department of Canberra, ACT Dr J van Rie, Bayer Dr B Saunders and Professor W Immunology, The University of Melbourne, Bioscience, Ghent, Belgium Britton Mycobacterial Research Group, Melbourne, VIC Centenary Institute of Cancer Medicine and Cell Biology, Sydney, NSW Dr Rebecca Haddock Professor Chris C Goodnow Involvement of ROS in obesity-related Professor Chris C Goodnow, and Dr Ian Parish hypertension Dr Edward M Bertram, Imaging proximal T cell signalling Associate Professor GG Drummond Associate Professor Guna Professor K Gaus Centre for Vascular and Associate Professor CG Sobey Department of Pharmacology, Monash Karupiah, Dr Anselm Enders Research, University of New South Wales, Sydney, NSW University, Melbourne, VIC and Dr Katrina Randall Systems approach to Inflammation and Immunity Professor R Ulevitch, Dr L Teyton

76 The John Curtin School of Medical Research Professor Caryl E Hill Associate Professor Gavin Dr Ben Kaehler Localisation of voltage dependent Huttley Development of Markov-process models calcium channels and gap junctions in the Signal processing techniques suitable to measure the influence of sequence- cerebral and systemic vasculature for analyses of epigenetic and DNA neighbourhoods on mutation dynamics Dr SL Sandow Department of sequence data Associate Professor VB Yap Pharmacology, School of Medical Dr J Epps School of Electrical Department of Statistics and Applied Sciences, The University of New South Engineering and Telecommunications, Probability, National University of Wales, Sydney, NSW The University of New South Wales, Singapore, SIngapore Blood pressure recordings in freely Sydney, NSW Coevolution of silk proteins moving animals Stochastic models of sequence Dr H Trueman CSIRO Ecosystem Dr R Brown Department of Physiology, divergence Sciences, Canberra, ACT Monash University, Melbourne, VIC Dr K Verbyla CSIRO Mathematical and Modulation of gap junctional coupling by Information Sciences, Canberra, ACT Associate Professor Guna mutations in connexin40 Development of a software library for Karupiah and Dr Geeta Dr A Ashton Division of Perinatal genomic biology; numerous other Chaudhri Research, Kolling Institute of Medical projects related to the evolutionary Research, Royal North Shore Hospital, dynamics of sequence divergence Modulation of the immune response by University of Sydney, NSW Professor R Knight Department of virus-encoded cytokine homologs Role of T-type calcium channels in Chemistry and Biochemistry, University of Professor M Buller St Louis University, vasoconstriction Colorado, Boulder, CO, US St Louis, MO, US Professor A Alcami Professor PB Hansen Department of Development of Markov-process models Centro de Biología Molecular Severo Cardiovascular and Renal Research, to measure the influence of sequence- Ochoa, Madrid, Spain University of Southern Denmark, Odense, neighbourhoods on mutation dynamics Induction of long-lived antiviral humoral Denmark Associate Professor VB Yap immunity Modulation of hemi channel function by Department of Statistics and Applied Dr T Newsome School of Molecular mutations in connexin4 Probability, National University of Bioscience, University of Sydney, Sydney, Singapore, Singapore Professor K Machaca Department of NSW Physiology and Biophysics, Weill Cornell Evolution of venom molecules Associate Professor R Brink Garvan Medical College-Qatar, Education City, Dr N Casewell Liverpool School of Institute for Medical Research, Sydney, NSW Doha, Qatar Tropical Medicine, Liverpool, UK Actin-based motility as a virulence Modulation of gap junctional coupling in mechanism and potential as an antiviral oocytes by mutations in connexin4 Associate Professor Gavin target Professor BJ Nicholson Department of Huttley and Dr Åsa Pérez- Dr T Newsome School of Molecular Biochemistry, University of Texas Health Bioscience, University of Sydney, Sydney, Sciences Center, San Antonio, TX, US Bercoff NSW Understanding the genetic causes of Pathophysiological significance of reverse Dr Lauren Howitt virulence in fungal pathogens signalling through membrane TNF Effect of diet-induced obesity on vascular Prof Dr rer nat W Meyer The University Professor A Alcami Centro de Biología tone of skeletal muscle and cerebral of Sydney Medical School, Westmead Molecular Severo Ochoa, Madrid, Spain arteries Hospital, Westmead, NSW Professor H Nevalainen and Professor I Dr TV Murphy Department of Physiology, Paulsen Department of Chemistry Associate Professor School of Medical Sciences, University of and Biomolecular Sciences, Macquarie Guna Karupiah, Dr Geeta New South Wales, Sydney, NSW University, Sydney, NSW Chaudhri and Professor Mechanisms by which oxidative stress Chris C Goodnow increases the contribution of T-type Dr Andrew James calcium channels to vascular tone Systems approach to immunity and Multimodal multifocal neuroimaging of Associate Professor G Drummond inflammation human visual cortex Department of Pharmacology, Faculty Professor R Ulevitch and Professor of Medicine, Nursing & Health Sciences, Dr S Vanni Helsinki University of B Beutler The Scripps Research Monash University, Melbourne, VIC Technology, Helsinki, Finland Institute, La Jolla, CA, US Professor A Multifocal evoked potential mapping of Aderem Seattle Biomedical Research human retinotopic visual area Institute, Seattle, WA, US Professor G Nolan Department of Microbiology and Dr S Inverso Pasteur Institute, Paris, Immunology, Stanford University, Palo France Alto, CA, US

Annual Review 2012 77 Professor Trevor D Lamb of Medicine, University of Extremadura, Professor Ted Maddess Badajoz, Spain Evolution of the vertebrate eye Multifocal visual evoked potentials Congenital leptin deficiency Professor SP Collin, Professor D Dr S N Abdullah Raja Isteri Pengiran Hunt and Associate Professor N Hart Dr T Delibasi Department of Anak Saleha (RIPAS) Hospital, Bandar School of Animal Biology, University of Endocrinology, Ankara Hospital, Ankara, Seri Begawan, Brunei Turkey Western Australia, Perth, WA Sources of triphasic waves in hepatic Recovery of human cone photoreceptors encephalopathy Associate Professor Brett following bleaching Dr I Al Homoud King Faisal Specialist Dr O Mahroo Department of Physiology, Lidbury Hospital and Research Centre, Saudi Development and Neuroscience, Viral diseases and genetics of the host Arabia University of Cambridge, Cambridge, UK response Polarisation sensitivity in squid eyes Associate Professor M Heise Professor Y Nagai Kokushikan Professor Julio Licinio Department of Genetics, University of University, Tokyo, Japan North Carolina, Chapel Hill, NC, US Translational studies in obesity Multifocal visual evoked potentials and Professor S Bornstein and Dr M Systematic review and meta-analyses as visual attention in multifocal pupillography a complementary technique to enhance Ehrhart- Bornstein University of Associate Professor Y Rosli Universiti predictions from pattern recognition , Dresden, Germany Kebangsaan Malaysia, Bangi Selangor, involved in a novel animal replacement Malaysia The International HapMap Consortium system Multifocal visual evoked potentials The International HapMap Professor M Ritkes-Hoitinga and Dr Consortium National Center for K Wever SYRCLE, Radboud University Dr MY Boon University of New South Biotechnology Information, National Nijmegen, The Netherlands Wales, Sydney, NSW Institutes of Health, Bethesda, MD, US Animal replacement alternatives via Identifying brain lesions in multiple computational methods sclerosis from MRI scans Professor Julio Licinio and Professor S-H Chung Biomedical Dr A Janke Centre for Advanced Professor Ma-Li Wong Science and Biochemistry, Research Imaging, University of Queensland, Brisbane, QLD Translational studies in stem cell research School of Biology, The Australian National University, Canberra, ACT Professor S Bornstein and Dr M Ehrhart- Bornstein University of Pattern recognition in pathology data Professor Ted Maddess and Dresden, Dresden, Germany and in vitro validation of diagnostic data Dr Marconi Barbosa networks Neuroendocrine outcomes of Texture discrimination inflammation and stress Associate Professor T Badrick Faculty of Health Sciences and Medicine, Bond Professor JD Victor Weill Cornell Professor ED London Departments University, Gold Coast, QLD Medical College, Cornell University, New of Psychiatry and Biobehavioral York, NY, US Sciences, and Molecular and Medical Metabolomic profiles and clinical Pharmacology, David Geffen School of microbiology of ME-CFS Medicine, University of California, Los Dr H Butt, Associate Professor P Dr Claudio A Mastronardi Angeles, CA, US Professor V Rettori Gooley and C Armstrong Bio21 Institute Translational studies in obesity Center of Pharmacological and Botanical and University of Melbourne, Melbourne, Professor S Bornstein and Dr M Studies, CEFYBO-CONICET-UBA, School VIC Ehrhart- Bornstein University of of Medicine, University of Buenos Aires, Knowledge discovery in pathology Dresden, Dresden, Germany Buenos Aires, Argentina databases for enhanced laboratory Neuroendocrine outcomes of Genetics of depression diagnosis inflammation and stress Dr V Andreev Department of Psychiatry G Koerbin ACT Pathology, The Canberra Professor V Rettori Center of and Behavioral Sciences, Center on Hospital, Canberra, ACT Pharmacological and Botanical Studies, Pharmacogenomics, University of Miami Immunology of ME-CFS CEFYBO-CONICET-UBA, School of Miller School of Medicine, Miami, FL, US Medicine, University of Buenos Aires, Dr C Dong Department of Neurology, Professor S Marshall Griffith Health Buenos Aires, Argentina University of Miami Miller School of Institute, Griffith University, Gold Coast, Medicine, Miami, FL, US QLD Pharmacogenetics of antidepressants Biomedical and clinical study of ME-CFS patients Professor A Llerena Department of Pharmacology and Psychiatry, Faculty Dr D Lewis CFS Discovery, Donvale Specialist Medical Centre, Donvale, VIC

78 The John Curtin School of Medical Research Professor Klaus I Matthaei Professor Christopher Dr Brian Parker New Mx1 mouse model for interferon Parish microRNA 9 time series analysis action in influenza virus infection Role of platelets in tumour metastasis Professor A Krogh The Bioinformatics Dr M Frese School of Health Sciences, Professor B Chong School of Center, Department of Biology, University University of Canberra, Canberra, ACT Pathology, The University of New South of Copenhagen, København, Denmark The role of the S100 multigene family in Wales, Sydney, NSW Frequency-domain analysis of ancient inflammation Studies of immune thrombocytopenia DNA nucleosome positioning Professor C Geczy Inflammatory Professor B Chong School of Assistant Professor JS Pedersen Diseases Research Unit, School of Pathology, The University of New The Bioinformatics Centre, Department Medical Sciences, The University of New South Wales, Sydney, NSW Professor of Molecular Biology, University of South Wales, Sydney, NSW L Khachigian Centre for Vascular Copenhagen, København, Denmark The role of IL-5 and eosinophils in gut Research, The University of New South allergy Wales, Sydney, NSW Dr Hardip Patel Assistant Professor S Hogan Division Nuclear localisation of heparanase and The evolution of sex chromosome and of Allergy and Immunology, Cincinnati other proteins dosage compensation mechanisms Children’s Hospital Medical Center, Professor R Stocker Department of Cincinnati, OH, US Dr P Waters Research School of Biology, Pathology, The University of Sydney, The Australian National University, The role of IL-5 and eosinophils in allergy Sydney, NSW Professor L Khachigian Canberra, ACT Dr D O’Meally Institute Professor M Rothenberg Division Centre for Vascular Research, The for Applied Ecology, University of of Pulmonary Medicine, Allergy and University of New South Wales, Sydney, Canberra, Bruce, ACT NSW Associate Professor S Rao Immunology, Cincinnati Children’s Hospital Transcriptome sequencing of two Medical Centre, Cincinnati, OH, US Faculty of Applied Science University of Canberra, ACT phenotypic mosaic Eucalyptus trees Parasite infection in gene deficient mice Development of a liposome-based TB Dr C Kuleim Research School of Biology, Dr L Dent Eosinophil Biology Laboratory, vaccine The Australian National University, Microbiology and Immunology, School Canberra, ACT Associate Professor J Triccas of Molecular and Biomedical Science, Transcriptome sequencing and differential Adelaide University, Adelaide, SA Department of Infectious Diseases and Immunology, University of Sydney, expression analysis of four Arabidopsis The biology of heparanase deficiency Sydney, NSW cultivars Dr M Hulett Department of Biochemistry, Heparan sulfate and Alzheimer’s disease Dr I Searle Research School of Biology, La Trobe University, Melbourne, VIC The Australian National University, Professor D Small Menzies Research Canberra, ACT Innate immunity in allergic asthma Institute, University of Tasmania, Hobart, Dr S Phipps School of Biomedical TAS The effect of sex reversal on brain gene expression patterns in lizards Sciences, University of Queensland, Novel angiogenesis inhibitors Brisbane, QLD Associate Professor T Ezaz Institute for Dr P Karuso Department of Chemistry Applied Ecology, University of Canberra, and Biomolecular Sciences, Macquarie Bruce, ACT Dr Maxim Nekrasov University, Sydney, NSW Dr M Kelso School of Chemistry, University of Immune genes during development of the A novel protease-dependent mechanism tammar wallaby that regulates the epigenetic landscape at Wollongong, NSW a genome-wide level Islet heparan sulfate and type I diabetes Mrs M Edwards Research School of Biology, The Australian National University, Professor SA Grigoryev Department Professor R Rodgers Department of Canberra, ACT of Biochemistry and Molecular Biology, Obstetrics and Gynaecology, University of Milton S Hershey Medical Centre, Penn Adelaide, Adelaide, SA Professor T Kay Generating high quality physical map of State University College of Medicine, St Vincent’s Institute, Melbourne, VIC Pogona vitticeps chromosomes Hershey, PA, US Immunosurveillance of MCA-induced Dr J Deakin Research School of Biology, How dynamic changes in the three- sarcomas in Th2-immune deficient mice The Australian National University, dimensional architecture of the genome Canberra, ACT Associate Professor L Simson Applied regulate cell fate Science, University of Canberra, ACT Adaptive evolution of genes in lizards Professor Y Ruan The Lackson Targeted mistletoe tumour therapy Professor A Georges Institute for Laboratory for Genomic Medicine, UConn Applied Ecology, University of Canberra, Health Center, Farmington, CT, US Associate Professor L Simson Applied Bruce, ACT Science, University of Canberra, ACT

Annual Review 2012 79 Effect of maternal asthma on placental Professor Thomas Preiss Translational control of the EBV-encoded gene expression nuclear antigen, EBNA1 A sustained dietary change increases Dr V Clifton University of Adelaide, epigenetic variation in isogenic mice Dr J Tellam Queensland Institute of Adelaide, SA Medical Research, Brisbane, QLD Associate Professor C Suter The Victor Chang Cardiac Research Institute, Developmental defects of the Dr Gilberto Paz-Filho Sydney, NSW Professor David Martin gastrointestinal tract caused by dysfunction of a RNA binding protein Congenital leptin deficiency Children’s Hospital Oakland Research Institute, Oakland, CA, US Professor P Tam Children’s Medical Dr T Delibasi Department of Research Institute, Sydney, NSW Endocrinology, Ankara Hospital, Turkey The prevalence and roles of 5-methylcytosine in eukaryotic Exploring the interface between Brain imaging in leptin-deficient humans transcriptomes RNA, enzymes and metabolites in Professor ED London Department of Associate Professor C Suter The cardiomyocytes Psychiatry and Biobehavioral Sciences Victor Chang Cardiac Research Institute, Professor M Hentze European and Semel Institute, David Geffen School Sydney, NSW Professor S Clark Garvan Molecular Biology Laboratory, Heidelberg, of Medicine, University of California, Institute of Medical Research, Sydney, Germany Los Angeles, CA, USA Professor MA NSW Mandelkern Department of Physics, The role of miRNAs in the generation of University of California, Irvine, CA, US Sequence diversity in the murine iPS cells cardiomyocyte miRNA population Clinical Endocrinology: Multinodular Professor A Nagy Lunenfeld- goitre, metabolic syndrome, obesity and Associate Professor D Fatkin and Tanenbaum Research Institute, Toronto, thyroid disorders Associate Professor C Suter The ON, Canada Professor S Grimmond Victor Chang Cardiac Research Institute, Institute for Molecular Bioscience, The Professor H Graf, Professor C Sydney, NSW University of Queensland, Brisbane, QLD Boguszewski, Professor GA de Carvalho and Dr V Borba Department Exploring the role of microRNA and Directed alteration of 3’UTR variation in of Endocrinology of the Federal University target processing variability in cardiac mammalian cells hypertrophy of Parana, Curitiba, Brazil Professor S Wilton Molecular Genetic Professor B Graham The Victor Chang Therapies Group, University of Western Dr Jason Potas Cardiac Research Institute, Sydney, NSW Australia, Perth, WA Identifying the Targets of miRNA Identification of miRNAs which target the Functional mapping of the dorsal column Regulation in Cancer oncogene TCTP nucleus: A new approach to sensory pathway evaluation following spinal cord Dr T Beilharz Monash University, Associate Professor U Bommer injury Melbourne, VIC Graduate School of Medicine, University of Newcastle, Newcastle, NSW Professor J Morley University of Yeast hEST1A/B (SMG5/6)-like proteins Western Sydney, Campbelltown, NSW contribute to environment-sensing Translational regulation and alternative adaptive gene expression responses splicing in neuronal stem cells The use of nanofibre material for nervous tissue regeneration Associate Professor J Heierhorst St Dr L Vardy Institute of Medical Biology, Vincent’s Institute of Medical Research, A*STAR, Singapore Dr D Nisbet Research School of Melbourne, VIC Engineering, ANU, Canberra, ACT Post-transcritional control of gene Designer RNA-binding proteins for expression in inflammation research and therapeutic purposes Mr Alvin Pratama Professor A Ostareck-Lederer and Professor J Mackay Sydney Medical PD Dr D Ostareck University Hospital Regulation of Tfh cells by microRNA-146a School, The University of Sydney, Sydney, Aachen, RWTH Aachen University, Professor D Baltimore Biology and NSW Dr David Segal UC Davis Genome Aachen, Germany Biological Engineering, California Institute Center, University of California at Davis, of Technology, Pasadena, CA, US CA, US Professor Jan Provis Ms TX Dinh, Dr M Jordan and Neuronal microRNA deregulation In vivo OCT imaging of the fovea in Professor Alan Baxter Comparative in response to Alzheimer’s disease premature infants Genomics Centre, James Cook University, amyloid-β Townsville, QLD Professor J Götz Brain and Mind Dr J Carroll Medical College of Wisconsin, Milwaukee, WI, US Dr R Brink Immunology Program, Garvan Research Institute, University of Sydney, Institute of Medical Research, Sydney, Sydney, NSW Ageing of the human retina and AMD NSW RNA interference and the Immune System Dr M Madigan Save Sight Institute, Dr A Hutloff Immune Defense Associate Professor N McMillan University of Sydney, Sydney, NSW Mechanisms Group, Robert Koch Diamantina Institute, The University of Regression of the hyaloid vasculature – a Institute, Berlin, Germany Queensland, Brisbane, QLD proteomic analysis of human fetal vitreous

80 The John Curtin School of Medical Research Professor L P Aiello Joslin Diabetes HIV-1 envelop antibody studies Dr Charmaine J Simeonovic Center, Harvard Medcial School, Boston, Dr R Center and Associate Professor MA, US Dr J Sebag VMR Institute Heparan sulfate expression in isolated D Purcell Department of Microbiology human islets and islet transplants and University of Southern California, and Immunology, The University of Huntingdon Beach, CA, US Dr M Melbourne, Melbourne, VIC Professor S Bornstein and Dr B Madigan Save Sight Institute, University Ludwig University Clinic Carl-Gustav- of Sydney, Sydney, NSW and Department Carus, Technical University, Dresden, of Optometry, University of NSW, Sydney, Dr Katrina Randall Germany NSW Professor A Sadun University of DOCK8 in T cells Heparan sulfate and heparanase Southern California School of Medicine, expression in human pancreas Los Angeles, CA, US Dr S Russell and Dr J Oliaro Peter MacCallum Cancer Centre, Melbourne, Clinical Associate Professor JD Structure and Function of the primate VIC Wilson Department of Endocrinology, macula The Canberra Hospital, Canberra, ACT Professor S Cringle and Professor DY Yu University of Western Australia, Perth, Dr Katrina Randall, Dr WA Professor P Martin University of Stephen Daley, Mr Daniel Dr Charmaine J Simeonovic Sydney, Sydney, NSW Hu and Professor Chris C and Professor Christopher Goodnow R Parish Dr Charani Ranasinghe The Anaef mutation in T cell development Protection of human islet beta cells by HIV-1 mucosal vaccines and murine heparin and HS-mimetics Dr J Roose University of California San influenza-HIV-1 challenge studies. Francisco, San Francisco, CA, US Professor T Kay, Dr H Thomas and Dr Dr J Stambas Deakin University and T Loudovaris Immunology and Diabetes CSIRO Animal Health Laboratories, Unit, St Vincent’s Institute, Melbourne, Geelong, VIC Dr Danny Rangasamy VIC TNF family members and immune Exploring the role of L1 retrotransposon responses to viral infection and tetramer and Rad21 in CRC Cancer Dr Charmaine J Simeonovic, studies Dr X Huiling Peter MacCallum Cancer Professor Christopher R Dr L Sedger School of Medical and Centre, Melbourne, VIC Parish and Ms Fui Jiun Molecular Biosciences, The University of Expression of LINE-1 retrotransposon as Choong Technology, Sydney, NSW an instability biomarker Mucosal HIV-1 and TB vaccines that can Professor JE Dahlstrom ACT Remodelling of the islet BM after islet enhance T-cell avidity Pathology, The Canberra Hospital, isolation and transplantation Professor A Ramsay Gene Therapy Canberra, ACT Professor R Rodgers Department Program, Louisiana Vaccine Centre, Analysis of epigenetic factors in mouse of Obstetrics and Gynaecology, The Louisiana State University Health embryonic neural stem cells exposed to University of Adelaide, Adelaide, SA Dr Sciences Centre, New Orleans, LA, US hyperglycemia H Irving-Rodgers School of Medical Science, Griffith University, QLD HIV-1 Pox viral-based vaccine vector Professor ST Dheen Department preparation & evaluation of Anatomy, National University of Dr D Boyle CSIRO Livestock Industries, Singapore, Singapore Dr Charmaine J Simeonovic, Australian Animal Health Laboratory, Insertional mutagenesis system to identify Dr Andrew Ziolkowski and Geelong, VIC epigenetic factors that control embryonic Professor Christopher R HIV-1 and vaccinia virus T cell immunity stem cells differentiation Parish studies in humans Dr N Lenka National Centre for Cell Science, Pune University Campus, Loss of islet heparan sulfate in T2D in db/ Professor A Kelleher Immunovirology db mice and Pathogenesis Program NCHECR, Ganeshkhind, Pune, India University of New South Wales, Sydney, Professor T Biden and Dr R Laybutt NSW and St Vincent’s Centre for Applied Dr Daniel Ryan Garvan Institute of Medical Research, Medical Research, Sydney, NSW Sydney, NSW Structural and functional analysis of a HIV/SIV macaque vaccine studies cancer-linked co-regulator complex Professor S Kent and Dr R De Professor Joel Mackay School of Rose Department of Microbiology and Molecular Biosciences, University of Immunology, The University of Melbourne, Sydney, Sydney, NSW Melbourne, VIC

Annual Review 2012 81 Dr Tanya Soboleva Professor David Tremethick Dr Krisztina Valter, Dr Generation of a knock-out H2A.Lap1 The role of histone variants in modulating Riccardo Natoli and gene model in mice using TALEN chromatin fibre dynamics Professor Jan Provis technology Dr K Luger Department of Biochemistry Oxygen-induced retinopathy and 670nm Professor P Koopman and Dr and Molecular Biology, Colorado State light J Bowels Institute for Molecular University, Fort Collins, CO, USA Dr A Kent, Professor J Dahlstrom, Dr Bioscience, The University of Queensland, Chromatin remodeling during early Brisbane, QLD R Essex and Dr A-L Mohamed ANU development Medical School, The Australian National Analysis of the H2A.Lap1 knock-out Dr A Peters Friedrich Miescher Institute University, Canberra, ACT and ACT mouse model for Biomedical Research, Basel, Health, The Canberra Hospital, Canberra, Dr Ruth Arkell Research School of Switzerland ACT Biology, The Australian National University, Chromatin remodeling during oogenesis Canberra, ACT Dr J Bowles Institute for Molecular Professor Carola G Vinuesa Bioscience, University of Queensland, Role of single nucleotide polymorphisms Dr Zan-Min Song Brisbane, QLD in the development of systemic lupus Neural stem cell transplantation therapy Chromatin function in differentiation and erythematosus in treating Hirschsprung’s disease in a rat cancer Dr D Gale Imperial College, London, model Professor SA Grigoryev Department UK Dr A Bowie Trinity College, Dublin, Professor H Young and Professor J of Biochemistry and Molecular Biology, Ireland Dr A Weber The University of Furness Department of Anatomy and Milton S Hershey Medical Centre, Penn Tübingen, Tübingen, Germany Dr R Neuroscience, University of Melbourne, State University College of Medicine, Brink Immunology Program, Garvan Melbourne, VIC Associate Professor Hershey, PA, US Institute of Medical Research, Sydney, D Croaker The Canberra Hospital, NSW Associate Professor S Alexander Canberra, ACT Westmead Hospital, Westmead, NSW Dr Krisztina Valter Dr M Alarcon-Riquelme University of Associate Professor The effects of VCP treatment in retinal Granada, Granada, Spain Professor P degenerations Petersen Molecular Pathology, University Christian Stricker of Tartu, Tartu, Professor GJ Kotwal Kotwal Information transfer in realistic networks Bioconsulting and Sullivan University, Neural-like signaling in germinal centre response Dr M McDonnell Institute of Louisville, KY, US Professor GJ Arason Telecommunications Research, University University of Iceland, Reykjavik, Iceland Professor C Doglioni Department of of South Australia, Adelaide, SA Photobiomodulation using 670 nm light in Pathology, San Raffaele Hospital, Milan, the retina Italy Professor Greg J Stuart Professor J T Eells University of Regulation of Tfh cells by microRNA-146a Wisconsin, Milwaukee, WI, USA Action potential initiation and interaction Dr D Baltimore Biology and Biological with inhibitory synaptic events Treatment methods in retinal degeneration Engineering, California Institute of Technology, Pasadena, CA, US Professor M Häusser The Wolfson Professor S Bisti University of L’Aquila, Institute for Biomedical Research, L’Aquila, Italy Roquin and RNA regulation University College, London, UK Retinal inflammation in retinal Dr J Babon The Walter and Eliza Role of HCN channels in absence degenerations and effects of 670 nm light Hall Institute for Medical Research, Melbourne, VIC epilepsy Dr M Madigan Save Sight Institute, Dr S Petrou Howard Florey Institute, The University of Sydney, Sydney, NSW and University of Melbourne, Melbourne, VIC Department of Optometry, University of Professor Carola G Vinuesa Professor S Berkovic Department of NSW, Sydney, NSW and Mr Roy Ramiscal Medicine, Austin Health, The University of Proteomic changes in damaged and 670 Tfh metabolism Melbourne, Melbourne, VIC Associate nm treated retinas Professor T O’Brien Department of Dr J Babon and Dr A Kallies The Dr U Mathesius Research School of Medicine, The University of Melbourne, Walter and Eliza Hall Institute for Medical Biology, The Australian National University, Melbourne, VIC Research, Melbourne, VIC Professor M Canberra, ACT Febbraio Baker IDI Heart and Diabetes The effects on 670 nm light in retinal Institutes, Melbourne, VIC Dr RG Jones damage McGill University, Montreal, QC, Canada Dr R Essex ANU Medical School, The Australian National University, Canberra, ACT

82 The John Curtin School of Medical Research Professor Bruce Walmsley Professor Ma-Li Wong Professor Ian G Young Mechanisms of central neuronal Neuroendocrinology aspects of Role of IL-3 receptor in myeloid leukaemia integration methamphetamine dependence Professor YZ Chen Fujian Medical Professor REW Fyffe and Mr AS Professor ED London Departments University, Fuzhou, China Deardorff Boonshoft School of Medicine, of Psychiatry and Biobehavioral Cytokine receptors Wright State University, Dayton, OH, US Sciences, and Molecular and Medical Pharmacology, David Geffen School of Dr J Murphy Molecular Medicine Medicine, University of California, Los Division, Walter and Eliza Hall Institute of Angeles, CA, US Medical Research, Melbourne, VIC Role of cytokines in allergic inflammation Professor PS Foster School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW

Australian Phenomics Facility Collaborations

Australian Phenomics Australian Phenomics China- Australia Centre of Network Project: ES cell to Network Project: Phenomics Research Mouse Service Australian Phenome Bank Professor H Tang Chinese Academy of Professor I Smyth Department of Cryopreservation Sciences, Institute of Biophysics, Beijing, China Biochemistry and Molecular Biology Dr D Hopwood Animal Resources and Department of Anatomy and Centre, Murdoch, WA Developmental Biology, Monash International Mouse University, Melbourne, VIC Australian Phenomics Phenotyping Consortium Australian Phenomics Network Project: RNAi Professor S Brown (Chair), Harwell MRC, Harwell Science and Innovation Network Project: ENU technologies Campus Oxfordshire, UK Variant Collection Professor R Teasdale Institute for Molecular Bioscience, The University of Melanoma Project and SNV Dr B Kile Walter and Eliza Hall Institute of Queensland, Brisbane, QLD Medical Research, Melbourne, VIC Detection Professor R Johnstone Peter Professor S Foote Menzies Research MacCallum Cancer Centre, Melbourne, Mr C Broadley Australian Genome Institute Tasmania, Hobart, TAS and VIC Research Facility Macquarie University, Sydney, NSW Dr L Winteringham Western Australian Institute for Medical Research Perth, WA Developing a new imaging Australian Phenomics and brain atlas tool Network Project: Mouse Systems Approach to Professor G Galloway and Dr A Janke Pathology Immunity and Inflammation Centre for Advanced Imaging, National Imaging Facility, University of Queensland, Professor J Furness University of Professor R Ulevitch The Scripps Brisbane, QLD Melbourne, Melbourne, VIC Research Institute, La Jolla, CA, US Dr T Kuchel South Australian Health and Framework Data Sets Medical Research Institute, Adelaide, SA Mutagenetix – A database of Mr A Gilbert Bioplatforms Australia, mutations and phenotypes Sydney, NSW induced by ENU Professor B Beutler University of Texas Southwestern Medical Center, Dallas, TX, US

Annual Review 2012 83 84 The John Curtin School of Medical Research Staff and Students lists

Department of Genome Biology Department of Immunology Eccles Institute of Neuroscience Department of Pathogens and Immunity Department of Molecular Bioscience Department of Translational Medicine APF and Animal Services School Administration School Services Students

Annual Review 2012 85 Genome Biology

Professor and Head of Computational Genomics Genome Diversity and Department Group Health Group

Tremethick DJ, BSc(Hons), (USyd), PhD Associate Professor and Leader Professor and Leader (MacqU) Huttley GA, BSc(Hons) (MacqU), PhD (UC Easteal, S, BSc(Hons) (St Andrews), Departmental Administrator Riverside) MBA, PhD (Griffith) Stenhouse J, BA Postdoctoral Fellows Postdoctoral Fellow Kaehler B, BSc (UNSW), BEng(Hons) Das D, BSc(Hons) (Presidency College, Alternatives to Animal UNSW, MQuantitative Finance (UTS), PhD Kolkata), MSc (Madurai Kamaraj), PhD Research Through (from July) (JNCASR, Bangalore) (until July) Bioinformatics Group Pérez-Bercoff Å, PhD (Dublin) (from Senior Technical Officer August) Associate Professor and Leader Tan X, BSc (Shandong), MSc (China Visiting Fellow Pharmaceutical) Lidbury BA, BSc(Hons) (Newcastle), PhD Verbyla K, BSc(Hons) (Adel), PhD (UMelb) Research Assistant Visiting Fellows Visiting Student Prichard Z, BSc(Hons) (UNSW), PhD Gahan M, BA/BSc(Hons), Postgraduate Diploma in Forensic Science (LaTrobe), Zhu Y, BSc(Hons), B Comm (from July) PhD (Monash) RNA Biology Group Computational and Richardson AM, BA(Hons) (Well), MStats, Professor and Leader PhD Conceptual Biology Group Preiss T, Dipl Chem (Philipps University Marburg Germany), PhD (Newcastle upon Visiting Student Professor and Leader Tyne), Habil (Heidelberg) Shang GF, Master of Medical Immunology Gready JE, BSc(Hons), PhD (USyd), (Tongji Medical University, China) FRACI Research Fellows Archer SK, BSc(Hons), PhD School Visitor (Statistical Senior Research Officers Consulting Unit, ANU) Cummins PL, BSc(Hons), PhD (USyd) Clancy JL, BSc(Hons) (UNSW), PhD Neeman T, BA (Harvard), MA, PhD (UNSW) Kannappan B, BSc (Madras), MSc, PhD (Virginia) (Pune) Postdoctoral Fellow Liao Y, PhD (UC Davis) Chromatin and Matthews PR, BSc(Hons), PhD Transcriptional Regulation Research Officers Senior Technical Officer Group Carlisle C, BSc (Massey) (May - June) Pagler E, BSc (Santo Tomas) Howles P, BA (USyd), BSc (Adel), Departmental Visiting Fellows Professor and Leader BSc(Hons), PhD (from September) (part- Barlin G, PhD, DSc (USyd), FRACI Tremethick, DJ, BSc(Hons), (USyd), PhD time) (MacqU) Cox G, BSc, PhD (UMelb), FAA Postdoctoral Fellows Postdoctoral Fellows Denborough M, MD, ChB (Cape Town), Alonso-Cantabrana H, BSc(Hons), PhD (U MD (UMelb), DPhil (Oxon), DSc (UMelb), Cook AJL, BMedSci(Hons) (USyd), PhD Alicante) FRCP (USyd) Vassilieva T, MSc (Novosibirsk) Morrison JE, BSc (USyd), MSc (UQ), Domaschenz RM, BSc(Hons) (Adel), PhD DPhil (Oxon), DSc (Cambridge) Research Assistants Nekrasov M, PhD (Heidelberg) Good G, BSc (MacqU) (part-time) Ryan DP, BSc(Hons) (USyd), PhD Mani-George A, BSc, (Mahatma Gandhi, India) MSc (Bharathiar, India) (from Soboleva T, MSc (MSU), PhD (MSU) August) Westman B, BSc(Hons) (USyd), PhD Wallace MJ, BSc (Wollongong) (from May)

Visiting Fellows Visiting Fellows Hapel A (from September) Armarego W, PhD, DSc (ULond), FRSC, Shannon MF, BSc(Hons), PhD (National FRACI University of Ireland) Bliznyuk A

86 The John Curtin School of Medical Research Immunology

Professor and Head of School Visitor Immune Tolerance and Department Wang J, MSc (NSW) Signalling Laboratory

Goodnow, CC, BVSc(Hons)(USyd), Editorial/Administrative Assistant Professor and Laboratory Leader BScVet (Hons)(USyd), PhD (USyd), FAA, Parish B, BSc (Madras), BSc, MSc, FRS Goodnow CC, BVSc(Hons) (USyd), GradDipCompStudies (UC) (part-time) BScVet(Hons) (USyd), PhD (USyd), FAA, Departmental Administrator FRS Diabetes/Transplantation Weil ETF Research Fellow Immunobiology Laboratory Bertram E, BSc(Hons) (Adel), PhD (Adel) Cancer and Vascular Fellow and Laboratory Leader CJ Martin Fellow Biology Group Simeonovic CJ, BSc(Hons), PhD Parish IA, BSc(Hons), PhD (WEHI) (from Professor and Leader Postdoctoral Fellows July) Parish CR, BAgrSc (UMelb), PhD (UMelb) Wu Z, MSc (UNSW), BM (ZhongShan), Research Fellows PhD (part-time from October) Fellow Daley S, BVSc (UQ), DPhil (Oxon) Ziolkowski A, BMedSc (Hons), PhD Freeman C, BSc(Hons) (Adel), PhD (Adel) Horikawa K, MD (Chiba), PhD (Tokyo)

Research Fellow Visiting Fellows Visiting Fellows McCullagh P, MBBS (UMelb), DPhil Quah B, BSc, PhD Cornall R, PhD (Oxon), MRCP (Lond), MD (UMelb) Fahrer A, BSc(Hons) (UMelb), PhD Postdoctoral Fellow Wilson JD, BSc(Hons), MBBCh, (UMelb) Coupland L, BSc(Hons), PhD, RN BAO(Hons), MD (Queens, Belfast), MRCP (UK), FRACP Hoyne G, BSc(Hons) (UWA), PhD (UWA) Visiting Fellows Randall K, MB (UNSW), BS (UNSW), BSc Chong G, MBBS (Hons), BMedSc Technical Officers (UNSW), FRACP, FRCPA, PhD (Monash) FRACS, FRCS (C) FRCS (E), Brown D, AssDipAppPath (CIT) (casual) Tze L, BSc (Beloit), PhD (Minnesota) Diplomate, American Board of Surgery Hamilton P, Certificate II (Animal Tech) Webb DC, DipMedLabSc (RMIT), BAppSc (USA) (CIT) (part-time) (UC), PhD (UC) Cooper PD, BSc(Hons) (ULond), PhD Jensen LM, BSc(Hons) (until June) (ULond), DSc (ULond) (from November) Wilson A, BSc(Hons) (UC), RN Popp SK, BSc, AssDipAppSci (Biol) (CIT) Hindmarsh EJ, BSc(Hons) (USyd), PhD (part-time) Research Technicians Li R, MD (China Medical University), PhD Balakishnan B, BSc(Hons) (Southern Cross) Immunogenomics Group Domaschenz H, PathTechCert (TAFE) McNaughton E, BSc(Hons) (UOtago), (until August) PhD (until September) Professor and Leader Howard D, BSc Price J, BSc(Hons) (UMelb), PhD (UMelb) Goodnow CC, BVSc(Hons) (USyd), BScVet(Hons) (USyd), PhD (USyd), FAA Law H (until July) Rao S, BSc(Hons) (Keele), PhD (Kings Miosge L, BSc(Hons), PhD College Lond) (until October) Laboratory Manager Sontani Y, BSc(Hons) (Murdoch), PhD Staykova M, PhD (USofia) Townsend M, PathTech Cert (TAFE), Sutcliffe E, BSc(Hons), PhD AssDipAppPath (Bruce TAFE) Laboratory Assistants Warren HS, BSc(Hons), PhD (UQ) Kanazawa Y (casual) (from April) Zhang D, BMed (2nd Military Medical Bioinformatics Laboratory Liu F (casual) (until May) University, PR China) Bioinformatics Fellow Senior Technical Officer Andrews TD, BSc(Hons) PhD Ramaciotti Immunization Bezos A, BSc (USyd), MSc (USyd) (part- Genomics Laboratory Bioinformaticians time) Cho V, BSc (Auck), PhD Senior Research Fellow Technical Officers Field M, BSc (Biol)/BSc (Computer Sci) Enders A, MD, PhD (Freiburg) Browne A, BA (part-time) (UBC) Postdoctoral Fellow Shao Y, BSc(Hons) Teh C, PhB(Hons), PhD (from March)

Annual Review 2012 87 Research Technician Newsome TP, BSc(Hons) (UMelb), PhD Visiting Fellow Barthel N, DipBiol (Freie Univ, Berlin) (Inst Molecular Pathology, Vienna) Stambas J, BSc(Hons) (UMelb), PhD Saunders BM, BSc(Hons) (UMelb), PhD (UMelb) Visiting Scholar (UMelb) (until June) Visiting Technical Officers Short A Scalzo A, BSc(Hons) (UMelb), PhD (UMelb) Buchanan A, BHealthSci (UC) Infection and Immunity Ravichandran J, BSc (India), BSc(Hons) Senior Technical Officers Group (UMelb) (part-time) Eldi P, MBBS (India) MSc (UQ) (part-time) Associate Professor and Leader Nasreen M, PhD (UTokushima, Japan) Translation Research Unit Karupiah G, BSc(Hons), MSc (Malaya), Technical Officers (joint with The Canberra PhD Patel V, PhD (from February) Hospital) Host Defence Laboratory Talukder S, PhD (Tokushima, Japan) Associate Professor and Leader (February-September) Cook M, MB, BS (USyd), FRACP, FRCPA, Associate Professor and Ter LK, BBioTech(Hons) (until June) PhD (USyd) Laboratory Leader Karupiah G, BSc(Hons), MSc (Malaya), Molecular Mucosal Vaccine Research Assistants PhD Chand R, BSc(Hons) (UMelb) (from Immunology Group January) Inflammation and Viral Fellow and Leader Srivastava U, MSc Immunopathology Ranasinghe C, BSc (Uni Rouen, France), Wilson A, BSc(Hons) (UC), RN (part-time) Laboratory MPhil (UColombo), PhD (UWA) Research Fellow Fellow and Laboratory Leader Jackson R, BSc(Hons) (Monash), PhD Chaudhri G, BSc(Hons), PhD (Edin)

Visiting Fellows Adjunct Fellow Belz G, BVBiol (UQ), BVSc(Hons) (UQ), Sedger L, BAppSci(Hons) (UTS), PhD PhD (UQ) (from June)

Eccles Institute of Neuroscience

Professor and Head Neuroimmunology & Suzuki N, BSc (Tsukuba), MMedSci (Tsukuba), PhD (Tokyo) Stuart GJ, BSc(Hons) (Monash), PhD, Cardiovascular Dysfunction FAA Laboratory Visiting Fellow Budisantoso T Departmental Administrator Leader Khalidi D Haddock RE, BSc (Wollongong), Development of Visual BSc(Hons), PhD Senior Technical Officer Diagnostics of Eye Disease Rodda GR, PTC Cerebral Cortex Group Group (from March)

Blood Vessel Group Associate Professor and Leader Professor and Leader Bekkers JM, BSc(Hons) (Griffith), MSc Maddess T, BSc(Hons) (UBC), PhD Professor and Leader (Manchester), PhD (Cambridge) Hill CE, BSc(Hons), PhD, DSc (UMelb) Research Fellows Postdoctoral Fellows Carle C, BSc(Hons), PhD Postdoctoral Fellow Choy J, BSc (UMS), PhD Sabeti F, BOptometry(Hons), Howitt L, BSc (USyd), PhD (UNSW) GradCertOcuThera, PhD

88 The John Curtin School of Medical Research Centre Manager Neuronal Signalling Group Neural Control Systems Muhammad A, BE (NEDUET), MESc Laboratory (from March) (UNSW), MESc (Nanyang), MBA (USQ), Professor and Leader PhD (UWS) (until August) Stuart GJ, BSc(Hons) (Monash), PhD Leader Webster B, BSc (from August) Potas JR, BMedSc(Hons) (USyd), PhD Brain Development (USyd) Administrative Assistant Laboratory Webster B, BSc (from August) Visiting Emeritus Professor Leader Synapse and Hearing Group Horridge A Song Z-M, MMSc (Jiamusi), PhD (Flinders) Professor and Leader Visiting Fellows Walmsley B, BE, PhD (Monash), DSc Bedford S Neuronal Signalling (UNSW) Levick W Laboratory Morgan I Visual Neuroscience Group Professor and Leader Yanti R Stuart GJ, BSc(Hons) (Monash), PhD Professor and Leader Penfold P Lamb TD, BE (UMelb), ScD (Cambridge), Postdoctoral Fellows Xiang F FRS, FAA Breton J-D, MSc, PhD (Strasbourg) Bell A Ikeda K, BA (UC Boulder), PhD Departmental Visiting Vidovic M Longordo F, MSc, PhD (Lausanne) Fellows Stronks C Edwards FR, BE, PhD (Monash) Hughes A Visiting Fellow Eilers J Hendry IA, BSc(Med), MB BS (USyd), Human Neuroimaging PhD (Camb) Group (from March) Retinal Cell Damage and Hirst GDS, BSc, PhD (Leeds), FAA Repair Group (from March) Jarvinen J Associate Professor and Leader James AC, BSc(Hons) (Adel), PhD Professor and Leader University Fellow and Valter K, MD, PhD, GradCert HE Postdoctoral Fellow Emeritus Professor Barbosa M, BSc, MSc, PhD (São Paulo) Postdoctoral Fellow Curtis DR, AC, MBBS (UMelb), PhD, Biswas S, PhD (from May) FRACP, FAA, FRS Visiting Fellow Inverso S Visiting Fellows Querubin A Neuronal Network Group Madigan M

Associate Professor and Leader Retinal Development and Stricker C, MD (Zurich), PhD (Bern) Aging Group (from March) Research Fellow Professor and Leader Cowan AI, BSc(Hons), PhD Provis J, BSc(Hons) (UNSW), PhD (UNSW) Neurophotonics Laboratory Postdoctoral Fellow Leader Rutar M, BMedSc(Hons), PhD Daria V, PhD (Osaka) Research and Body Donation Co-ordinator Natoli R, BSc(Hons) (USyd), PhD

Annual Review 2012 89 Pathogens and Immunity

Professor and Head of CJ Martin Fellow Laboratory Technical Staff Department Ellyard J, BAs, BSc(Hons), PhD Hu X, BSc (Beijing Institute of Technology) (until May) Vinuesa CG, LMS(MBBS) (Madrid), Postdoctoral Fellows Jerjen R (from November) (casual) DRCOG (Lond), MSc, PhD (Birmingham) Athanasopoulos V, BSc(Hons), PhD (UMelb) Martin J Department Administrator Srivastava M, MSc (Rewa) (part-time) Morales D Duan T, MBBS (Nanjing), PhD Sweet R, BSc (UCLA), MSc (Yale), MPhil Williams N (Yale), PhD (Yale) Humoral Immunity and Research Assistant Autoimmunity Group Visiting Fellows Lee SK, MBioTech (Flinders) (September Papa I, MPhil (Milan) - December) Elizabeth Blackburn NHMRC Walter G, BA (Cantab), MBChB Research Fellow (), MRCP (UK), MD Vinuesa CG, LMS(MBBS) (Madrid), DRCOG (Lond), MSc, PhD (Birmingham)

Molecular Bioscience

Professor and Head of Visitor Cytokine Molecular Biology Department Rosenberg M, PhD and Signalling Group

Board PG, BSc(Hons), PhD (UNE) (until Professor and Leader September) Cancer Metabolism and Young IG, MSc (UMelb), PhD Dulhunty AF, BSc (USyd), PhD, DSc Genetics Group (UNSW) (from September) Postdoctoral Fellows Fellow and Leader Abdus F, BSc(Hons) (Bangladesh), MSc Departmental Administrator Blackburn A, BSc(Hons) (UNSW), PhD (UWSyd), PhD (from March) Khalidi D (until February) Laboratory Technician Chen J, BSc, (China), MMed (China), PhD Mitigas R (from February) Rooke M, BMedSci (Pharm Sci) (CSU) (Flinders) (until March) Biomolecular Interactions Visiting Fellows Cardiac and Skeletal Muscle Group Chen J, BSc, (China), MMed (China), PhD Proteomics Group (Flinders) (from March) Fellow and Leader Murphy J, BSc, PhD Leader Casarotto MG, BSc(Hons) (UMelb), PhD Beard NA, BAppSci(Hons) (LaTrobe), PhD Visiting Scholar (UMelb) Jiang H, BSc (China), MSc (China), PhD Postdoctoral Fellow Laboratory Technician (China) (from October) Janczura M Norris NC, BSc (Adv)(Hons) (USyd), PhD School Visitor (York) Technical Assistants Khan T, BSc (August –October) Technical Officer Ayad S, BSc (Assuit, Egypt) (from April) Technical Officers Aditya S, BBiotech(Hons) (from August) Kerdo E, BSc (from September) Dai J, BSc, MBiotech (from March) Thekkedam C, BScBioTech(Hons) Visiting Fellows (Wollongong) (from April) Ewens C Fan J, BSc (Fudan), MSc (Fudan), PhD Wen B, MB (China), MSc (China), PhD (Auck) (from March) Lim PS, BMedSci, PhD Zafar A, PhD

90 The John Curtin School of Medical Research Epigenetics and Genome Laboratory Technicians Laboratory Technicians Stability Group Cappello J, BSc (UC), AD AppSciAnSci Damcevski WB, AssDipAppScience (CIT) (CIT) (until January) Fellow and Leader Peile M, DipAnTech (CIT) (until January) Taylor HI, (until October) Rangasamy D, MSc, MTech (India), PhD Tummala P, BSc (Nagarjuna U) MSc (UK) (MSU), PhD (OU) Vaccine Immunology Group (until December) Membrane Physiology Muscle Research Group and Ion Channel Signaling Professor and Leader Group (until February) Professor and Leader Ramshaw IA, MSc (Brunel), PhD Dulhunty AF, BSc (USyd), PhD, DSc Research Fellow and Leader (UNSW) Laboratory Manager Tierney ML, BSc, MSc (Otago), PhD Medveczky CJ, AssocDipTechBiol (TAFE) Senior Research Advisor (part-time) Research Assistant Gallant E, PhD (Minnesota) Visiting Fellow Curmi J, BOptom(Hons) Research Fellow Lee E, BSc(Hons), PhD Beard NA, BAppSci(Hons) (LaTrobe), PhD Molecular Genetics Group (until May)

Professor and Leader Postdoctoral Fellows Board PG, BSc(Hons), PhD (UNE) Karunasekara YA, MD (USSR), PhD

Fellow Mirza S, BSc(Hons) (Dhaka), MSc(BioTech) (UNSW), PhD Blackburn A, BSc(Hons) (UNSW), PhD (until May) Talukder S, BSc(Hons) (Dhaka), MSc(Dhaka), PhD (Tokushima) (until Postdoctoral Fellows February) Liu D, PhD (USyd) (until March) Visiting Fellow Theodoratos A, BSc(Hons)(USyd), PhD Tierney L, BSc, MSc (Otago), PhD (from Zhou H, MSc (ShenYang Agricultural), February) PhD (Institute of Botany, Chinese Academy of Sciences) (until January) Senior Technical Officer Pace S, BSc (UTS) Visiting Fellows Baker R, BSc(Hons)(UNSW), PhD Laboratory Technicians Coggan M Kumarasinghe R (until July) Dahlstrom J, MBBS(Hons), FPAC, PhD, Segovis C (until August) FRCPA, GradCertEdSt Stivala J Hayes MT, BSc (USyd), MSc (USyd), Dip Ed (Tert) (UNE), PhD (QUT) (from October) Stem Cells and Gene Lee E, BSc(Hons), PhD (from December) Targeting Group Liu D, PhD (USyd) (from March)Shield A, BBiotech(Hons) (Flinders), PhD (Flinders) Professor and Leader Matthaei KI, BSc(Hons) (UNSW), PhD Ramshaw IA, MSc (Brunel), PhD (from December) Visiting Fellows Visiting Scholar Barharvand, H Takemura K, PhD (from August) Frese M, BSc (Osnabrück), PhD (Freiburg)

Annual Review 2012 91 Translational Medicine

Professor and Head of Technical Officers Translational Genomics Department Cai Y, BMed (Bejing Medical University, Group China) Licinio J, MD (Universidade Federal da Associate Professor and Group Bahia, Brazil), FAPA, FRANZCP Koskinen A Leader Departmental Administrator Registered Nurse Arcos-Burgos M, MD, PhD (University of Vitler L Lindsay K, AssDipSc (CSU) (until May) Cauca, Colombia) Visiting Fellows Technical Officer andL aboratory Translational Medicine Boguszewski CL Manager Group Rettori V Weaver L, DipLabTech (CIT) (until February) Professor and Group Leader Licinio J, MD (Universidade Federal da Pharmacogenomics Group Technical Officer Bahia, Brazil), FAPA, FRANZCP Professor and Group Leader Cai Y, BMed (Bejing Medical University, China) Research Fellows Wong M-L, MD (São Paulo, Brazil), Mastronardi CA, PhD (Buenos Aires, FRANZCP Argentina) Technical Officer and Laboratory Paz-Filho G, MD (Universidade Federal do Manager Paraná, Brazil) Weaver L, DipLabTech (CIT) (until Technical Officer and Laboratory February) Manager Technical Officer Weaver L, DipLabTech (CIT) (until Cai Y, BMed (Bejing Medical University, February) China)

APF and Animal Services

Director Departmental Administrator Australian Phenome Bank O’Keefe R Winslade SL, BA(Hons) (UNE), PhD (UNE) Phenome Bank Curator Chief Scientific Officer Veterinarian Read SH, BSc(Hons) (Adel), PhD (Adel) Glasson S (until August) Goodnow CC, BVSc(Hons) (USyd), Cryopreservation and IVF BScVet (Hons) (USyd), PhD (USyd), FAA, FRS Scientific Programs Coordinator Butterworth C, Cert IV Vet Nursing (CIT), Head of Animal Services Scientific Programs Manager Dip AppSci (CIT) Fowler S, BSc, BVMS (Murdoch) Balakishnan B, BSc(Hons) IVF and Cryporeservation Head of International Programs Scientific Project Coordinators Technician Bertram E, BSc(Hons) (Adel), PhD (Adel) Adams V, Cert III Path, Cert IV Vet Nursing Williams NJ, BAnVetBioSc(Hons) (USyd) (CIT) (until April) Scientific Business Manager Craven A, BAnimalSci (JCU) (on leave) Dobbie MS, BAppSc (UTS), MSc (USyd), Quarantine Coordinator PhD (Lond) Kofler J, DipAnTech (CIT), BSc Ross N, RLAT, Dip AppSci Animal Tech Tunningley R, BMedSci (CIT) Head of Scientific Programs Sjollema GE, BSc(Hons) MFM Scientific Project Team Quarantine Technician Technician Hunt B Liaison Officer Lorenzo A, BSc Biol (RP) Hewitt L, BMedSci (UC)

92 The John Curtin School of Medical Research Information Technology Experimental Colony Coordinator Petty K Burke H Prewett B IT Manager Reid C Wu P, BSc(Hons), BCompSci (Canada) Containment Suite Coordinator Clydesdale M Sibley B Programmers Sparrow M Fang Y Production Colony Coordinator Spencer C Ma H Bolton S-M Walker K (until February) Quinn G Technicians Walker L (until November) Shaw F Arthur M Watson D Barker Ay Young S Genomics Boljun M Zhang L (until October) Head of Genomics Research Bruckner D (until November) Building Maintenance Supervisor Whittle B, BSc(Hons) Burke J Hosking A Chau KS, Dip Animal Tech (CIT) Next Generation Sequencing Cover G Storeperson/Maintenance Coordinator Assistant Zhang Y, BSc, MSc (China) Delguime F (until July) Smith D Elliot N (until May) Genotyping and Mapping Ellis S (until February) Coordinator Figueroa S Mann D, BSc(Hons) (from November) Fook N (until July) Genomics Technical Officers Fowlie C Agrawal P, BSc, MSc, PhD (India) Gooding D (until March) Fitzgerald L, AssocDip Animal Sci, Cert IV Vet Nursing (CIT) Haas P Gao J, BSc (China), MBiotech (Hons) Hamilton R (from August) Hartley S Hamilton A, Dip Med Laboratory Tech Hebda D (until July) (CIT) (until October) Hebda M Liang R, BSc, MSc (China) Howe C (until March) Liu M, BSc, MSc (China) Irvin M Palkova A, BBus (QUT), BSc(Hons) (UQ) Jackson G (until November) Sayeed S, BSc, MSc (Bangladesh), PhD Jarvis L (UK) Kaya MS, BSc (UNewcastle) Animal Services Lin Q Lockley J Manager Operations Looms P (until March) Bowditch K Lorenzi L Campbell K (on leave) McPharlin J (until October) Training & Compliance McWilliam D Coordinator Pennock C (until July) Gooding D

Annual Review 2012 93 BRF and GDU

Manager Proteomics Team Palmer S, BSc(Hons), MBA (Tech McAndrew K, AssDipAppSci (UC) Management) (La Trobe) (returned from Zhang K, MSc (Fudan), PhD leave in July) Genome Discovery Unit Acting Co-Managers (until July) Buckley B, BA(Hons) (UQ) Higgins A, CBLT (USQ) Chuah A, BEng(Hons) (NUS) Milburn P, BSc(Hons), PhD (Sheffield) Jack C, BSc (Wellington) Technical Specialist Parker B, BSc (UQ), MBBS (UQ), PhD Milburn P, BSc(Hons), PhD (Sheffield) (USyd) Patel H, BPharm, MBiotech, PhD Genomics Team Shao L, BSc Cripps T, BSc(Hons) Higgins A, CBLT (USQ) Honorary Visitor Ohms S, MBChB, ME, PhD () Gock A, BAppSci (CSU) Peng K, PhD (Wuhan) Administrative Assistant Zhang K, MSc (Fudan) PhD Stenhouse J, BA

SCHOOL SERVICES

Facilities and Services Microscopy and Cytometry Technical Services Resource Facility (MCRF) Manager Manager Coombes D Head Coombes D Operations Assistant Gillespie CM, GradCertMic (USyd) Technical Officers Ciuffetelli L Histologist Cremer P Senior Storeperson Prins AS, BAppSci (RMIT) Gair L Clements R Flow Cytometry Specialist Jordan T Kynoch M Storeperson Vohra H, MSc(Hons) (Punjab), PhD (PGIMER) Percival M Talbot A Flow Cytometry and Microscopy Rhall G Media & Washup Operator Scharrer E Devoy M, BSc(Hons) Administrative Assistant Manager Dowling E Coombes D

Supervisor and Technical Officer Gilmartin L, Cert III Lab Skills (CIT)

Technician Munday K

94 The John Curtin School of Medical Research School Administration

School Administration Outreach and Communications Unit Director Licinio J, MD (Universidade Federal da Manager Bahia, Brazil) FAPA, FRANZCP Nicol MJ, BSc (Wollongong), BSc(Hons), Deputy Director PhD Board PG, BSc(Hons), PhD (UNE) Senior Multimedia Officer Business Manager Edwards K, PhotCert Coombes D (Acting) (until February) Education Lillicrap G (from February)

Executive Assistant to Director Associate Director Education and Medical Sciences Graduate Vitler L Convener Reception Cowan A, BSc(Hons), PhD, GradCertHE Patel A Student Administrator Safety & Training Riley W

Advisors Glasson S (from August) McKenzie K, AssDipAppSci (Animal Sci) (CIT), IT Cert III (CIT) (until September)

Annual Review 2012 95 Students

PhD Students Khanna M, BBiomedSci(Hons) (Victoria, Vassilieva T, MSc (Novosibirsk) Wellington) Abdool Z Velez J Kolic M Abraham MJ, BSc (UTas), MPhil Wang J, BBiomedSc(Hons) (UMelb), Larena M, BSc, MD BSc(Hons) (UMelb) Achuthan S Lee E, BSc, MSc (UC) Wijesundara D, BBiotech(Hons) Agahari F, BSc(Hons) (Japan) Lee S, BBiomedSci, MSc (Auck) Willemse H, BSc(Hons), MSc Agrawal A, BSc, MSc (JNKVV, Jabalpur) Dipl Bioinformatics (BAB, Bangalore) Lee S-K, BSc(Hons), MBiotech (Flinders) Wium E, BMedSci(Hons) Al Rumaih Z, BSc (Saudi Arabia), Li J, BMedSci(Hons) Wong R MBiotech (RMIT) Li L, BSc(Biotech) Xi Y, BEng (Jilin, China), MSc (Biotech) Albarracin R Mapp S, MBBS (UMelb), FRACP, FRCPA (Flinders) Ali E Mei Y, BSc(Hons) (Ottawa) Yabas M, MPhil Alshekaili J, BSc, MD Menon D, BBiotech, MBiotech Yap J, MBioTech(Hons) (from October) Altin J, PhB(Hons), LLB(Hons) (until Mishra A, BSc, MSc (Nepal) March) Mohan A, BTech (India) Anuar ND, BSc(Hons), MSc (Malaysia) Morse A Bell S, BSc(Hons) Morton S, BSc(Hons) Bergmann H, BVetSc (Hanover) Newman S, BSc(Hons) Bock T, BSc(Hons) Pratama A, PhB(Hons) Brew JM, BMedSci(Hons) Ramiscal R, BSc(Hons) Chan S-Y, BBiotech(Hons) Ratnadikawara M Chang PP, BSc (Malaya), MSc (Malaya) Rebbeck R, BMedSci(Hons) Chaston D, BSc(Hons) Robertson J, BSc(Adv)(Hons) Chen L Rudinski S, BSc(Hons) Cho E, BSc (Auck), GradDipSci (Auck) Sabouri Z, MD Choong FJ, BMedSci(Hons) Samarasinghe K Eldi P, MBBS (India), MSc (UQ) Saxena K, BBiotech Galgamuwe R, MBBS, MSc (Sri Lanka) Seamons J Gang B, BBiomedSci (Otago) Shen Q, MBiochem Go M-A, BSc, MSc (U Philippines) Sibritt T, BSc(Hons) Han S-Y, BSc(Hons) Simon Davis DA, BSc(Hons) (Adel) Hadjincalou A Singh M, BSc(Hons) (Otago) Hanna A, BSc(Hons) Sinha D, BSc, MSc (India) Hausner S Srivastava M, MSc (Rewa) Hu D, BMedSci(Hons) (USyd) Stojakovic A Huang H, BBiomedSci, MSc (NZ) Tan A, BBiotech(Hons) Hussain M, BSc(Hons) Tan X, BSc, MSc Hynes C, BSc(Hons) Teh C, PhB(Hons) Jeelall Y, BBiomedSci(Hons) (UMelb) Townsend D, BAppSci(Hons) (UC), Ji J, BSc(Hons) (USyd) BForensicSci (UC) Jiang S, MBBS FRACP Tran L Johnson-Saliba M, PhD Trivedi S, BBiotech, MBiotech (Research) Jones S, BMedSci(Hons) (UNSW) Tuazon J, BSc, MD Khan A (until March) Vaidya P

96 The John Curtin School of Medical Research MPhil Students MTranslational Medicine Choi S Students Pearce J Barry P Ravichandran J, BSc(Hons) (UMelb) Forster R Li Z Honours Students Zhang Y Batchelor E, BSc Zhao S Feakes D Giles A Work Experience Students Hu D Licinio A Jerjen R Wiley A Joseph-Hauser H McLennan N, BSc Research Placement Perera T Students Rogers A, BSc Aw V Saikal A Bruggeman K Soetanto R Dhounchak S Tang S-M Fam HL Williams J Kaya S Li J MBiotech (Research) Mei Z Student Muhereza A

Yuen D Silva A Sofoulis L MNeuroscience Students Ugool M Alexander P Wong G Espinoza-Oyarce D Volunteers Hammado N Haque F Haque F Martenzon H Iyengar L Owens-Walton C Mansuri H Pillai E Shelly S Qin M Zhu S Ravi I Visiting Scholar See J Masle-Farquhar E (from July) Sharp G Zinamidar A

Annual Review 2012 97 98 The John Curtin School of Medical Research Publications, Presentations and Community Outreach 2012

The 2012 list of publications from The John Curtin School of Medical Research includes peer reviewed journal articles reviews, short communications and book chapters. Listed here are the presentations made by staff and students of JCSMR at local, national and international research institutions, conferences and workshops throughout the year. Staff and students of the School continue to sit on numerous editorial boards, to assist with national and international granting bodies as expert assessors, and to belong to many scientific societies. They are also involved with community activities outside the School. Some of their activities are listed here.

Annual Review 2012 99 Publications

Abdullah, SN, Aldahlawi, N, Rosli, Y, for thousands of new mouse models. Board, PG and Hutchinson, I (2012) A Vaegan, Boon, MY and Maddess, T Open Biology 2:120061 fluorescence-based microtiter plate assay (2012) Effect of contrast, stimulus density, Anstey, KJ, Christensen, H, Butterworth, for gamma-glutamylcyclotransferase. and viewing distance on multifocal P, Easteal, S, Mackinnon, A, Jacomb, Analytical Biochemistry 420(2):177-181 steady-state Visual Evoked Potentials T, Maxwell, K, Rodgers, B, Windsor, T, Bornschein, A, Paz, G, Graf, H and de (MSVs). Investigative Ophthalmology and Cherbuin, N and Jorm, AF (2012) Cohort Carvalho, GA (2012) Treating primary Visual Science 53:5527-5535 profile: The Path through Life project. hypothyroidism with weekly doses of Abdullah, SN, Vaegan, Boon, MY and International Journal of Epidemiology levothyroxine: A randomized, single-blind, Maddess, T (2012) Contrast-response 41(4):951-960 crossover study. Arquivos Brasileiros de functions of the multifocal steady-state Arcos-Burgos, M, Londoño, AC, Endcrinologia e Metabologia 56(4):250- VEP (MSV). Clinical Neurophysiology 123 Pineda, DA, Lopera, F, Palacio, JD, 258 (9):1865-1871 Arbelaez, A, Acosta, MT, Vélez, JI, Bornstein, SR, Ehrhart-Bornstein, M, Ahamed, MBK, Aisha, AFA, Nassar, ZD, Castellanos, FX and Muenke, M (2012) Androutsellis-Theotokis, A, Eisenhofer, Siddiqui, JM, Ismail, Z, Omani, SMS, Analysis of brain metabolism by proton G, Vukicevic, V, Licinio, J, Wong, ML, Parish, CR and Majid, A (2012) Cat’s magnetic resonance spectroscopy Calissano, P, Nistico, G, Preziosi, P and Whiskers Tea (Orthosiphon Stamineus) ((1)H-MRS) in attention-deficit/ Levi-Montalcini, R (2012) Chromaffin cells: extract inhibits growth of colon tumor hyperactivity disorder suggests a The peripheral brain. 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Advances in A, Williams, R, Huttley, GA and Experimental Medicine and Biology Tremethick, DJ (2012) A unique Ong, SHL and Whitworth, JA (2012) 723:31-6 H2A histone variant occupies the Glucocorticoid-induced hypertension and transcriptional start site of active genes. the nitric oxide system. Expert Review of Rutar, M, Natoli, R, Provis, J and Valter, K (2012) Complement activation Nature Structural and Molecular Biology Endocrinology & Metabolism 7(3):273- 19(1):25-31 280 in retinal degeneration. In: Retinal Degenerative Diseases. Eds: M LaVail, Squires, JE, Patel, HR, Nousch, Paz-Filho, G and Graf, H (2012) J Ash, R Anderson, J Hollyfield Christia. M, Sibbritt, T, Humphreys, DT, Treatment and follow-up of differentiated Springer. pp31-36 Parker, BJ, Suter, CM and Preiss, thyroid cancer. In: Endocrinologia Clínica Rutar, M, Natoli, R and Provis, JM T (2012) Widespread occurrence of 5th Ed. Ed: L Vilar. 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104 The John Curtin School of Medical Research 109(11):E622-E622 (Lond) 36(10):1366-1369 Wong, ML, Dong, C, Andreev, V, Stuart, GJ (2012) Dendritic spikes veto Theodoratos, A, Wilson, LO, Gosling, Arcos-Burgos, M and Licinio, J (2012) inhibition. Neuron 75(5):744-746 KM, and Fahrer, AM, (2012) Splice Prediction of susceptibility to major variants of the condensin II gene Ncaph2 depression by a model of interactions Suzuki, N and Bekkers, JM (2012) of multiple functional genetic variants Microcircuits mediating feedforward include alternative reading frame translations of exon 1. The FEBS Journal and environmental factors. Molecular and feedback synaptic inhibition in the Psychiatry 17(6):624-633 piriform cortex. 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Annual Review 2012 105 Presentations

Associate Professor Associate Professor John International Society for the Study of Mauricio Arcos-Burgos Bekkers Xenobiotics (ISSX), Dallas, TX, US The role of the glutathione-linked enzymes Translational Genomics: On the Right Inhibitory microcircuits in the primary in the metabolism and detoxification of Track olfactory cortex therapeutic drugs The 3rd Bootes Course on Translational Symposium Speaker: 33rd Annual Symposium speaker: 10th CSSX Medicine: The Pathway from Discovery Meeting of the Australasian Neuroscience Conference and 3rd ISSX-CSSX Joint to Healthcare, The John Curtin School of Society, Gold Coast, QLD Workshop, The Chinese Pharmaceutical Medical Research, The Australian National Making sense of scents: The University, Nanjing, China University, Canberra, ACT neurophysiology of olfaction Translational Genomics: Applications to Plenary Lecture: Kioloa Neuroscience Ms Cassandra du Boulay Alzheimer’s Disease and ADHD Symposium, ANU Coastal Campus, Mouse cryopreservation and IVF Brain and Mind Congress, Medellin, Kioloa, NSW Workshop presentation: Australian Colombia Excitability and hyperexcitability in the and New Zealand Laboratory Animal Advances in Translational Genomics primary olfactory cortex Association (ANZLAA) Conference, University of Rosario, Bogota, Colombia Centre for Neuroscience, Charité- Brisbane, QLD Humboldt University, Berlin, Germany Dr Nicole Beard Cortical sensory processing and epilepsy: Dr Anneke Blackburn Insights from the olfactory system Acute chemotherapeutic treatment Targeting cancer metabolism with Queensland Brain Institute, Brisbane, induces chronic phosphorylation and dichloroacetate thiol modification of the cardiac ryanodine QLD Invited Seminar: Department of Oncology, receptor Cells and circuits for the cortical University of Oxford, Oxford, UK 56th Annual Meeting of the Biophysical processing of odours Society, San Diego, CA, US Symposium Speaker: 3rd UWS Sensory Dr Jean-Didier Breton Chemotherapy and cardiotoxicity - the Neuroscience Symposium, University of cardiomyocyte Ca2+ signalling connection Western Sydney, Campbelltown, NSW How GABAB receptor regulates neuronal excitability in the cerebral cortex? 60th Annual Scientific Meeting of the Cardiac Society of Australia and New Dr Edward M Bertram School of Biomedical Sciences and Pharmacy, University of Newcastle, Zealand, Brisbane, QLD Australian Phenomics Workshop Newcastle, NSW Ryanodine receptor dysfunction in Australia-European Union 2nd Workshop Somatic and dendritic GABA receptors cardiotoxicity and heart failure on Research Infrastructure, Brussels, B regulate cortical neurons excitability via Gage Conference on Muscle Excitation- Belgium different mechanisms Contraction Coupling, Canberra, ACT Linking causal relationships between Fundamental Neuroscience Department, In vitro interactions between junctin and genes and phenotypes of the immune Faculty of Medicine, University of Geneva, the ryanodine receptor (RyR1/RyR2) system through large scale ENU Geneva, Switzerland Gordon Conference on Muscle Excitation- mutagenesis of the mammalian genome Contraction Coupling, Les Diableretes, National Institute of Immunology, Delhi, Switzerland India Mr Bob Buckley Next Gen Mouse Models for Interpreting data on Autism Spectrum Dr Andrew Bell Understanding Human Disease Disorders from (a few) Australian Government sources A fresh look at how the middle ear Wuhan Institute of Virology, Chinese ASfAR, Macquarie University, Sydney, muscles work. Academy of Sciences, Wuhan, China NSW Live Video Presentation: Opening of Next Gen Mouse Models What is Bioinformatics? World Hearing Centre, Kajetany, Poland International Mouse Phenotyping Video Presentation: Australian Pressure model for human middle ear Consortium, Jeju Island, South Korea Bioinformatics Network (initiative of muscle function Bioplatforms Australia, CSIRO, EMBL Eccles Institute of Neuroscience seminar, Professor Philip Board Australia) The John Curtin School of Medical The impact of GSTZ1-1 and Research, The Australian National dichloroacetic acid on drug metabolism University, Canberra, ACT Symposium speaker: 18th North American Regional Meeting of the

106 The John Curtin School of Medical Research Dr Corinne Carle Mr Aaron Chuah From mice to humans (and back) in understanding immune disease Combining color with luminosity: green on Genome Discovery Unit: GainiNG Data red pupil perimetry in glaucoma Usability The 3rd Bootes Course on Translational Medicine: The Pathway from Discovery 20th International Visual Field and Imaging Bioinformatics Microsymposium, to Healthcare, The John Curtin School of Symposium, Melbourne, VIC Research School of Biology, The Medical Research, The Australian National It’s not what you show, it’s the way Australian National University, Canberra, University, Canberra, ACT ACT that you show it: Stimulus presentation Genetics of primary immune deficiency variants for multifocal pupil perimetry in GDUserv Bioinformatics Computational glaucoma Resource Usage Guidelines 23rd Annual Scientific Meeting, Australasian Society for Clinical Australian Ophthalmic and Visual Techniques in Computational Genomics, Immunology and Allergy, Wellington, NZ Sciences Meeting (AOVSM), Melbourne, The John Curtin School of Medical VIC Research, The Australian National Dr Lucy Coupland When 1 + 1 doesn’t equal 2: Gain-control University, Canberra, ACT in the pupil response pathway Variant Discovery: an overview of current Manipulation of self-recognition systems to prevent antibody-mediated ARC Centre of Excellence in Vision best practices thrombocytopenias Science Annual Retreat, Murramurang, Workshop: Bioinformatics for High NSW Throughput Sequencing, The John Curtin Australian Institute of Medical Scientists Conference, Wagga Wagga, NSW Without the click of a button: Objective School of Medical Research/ Research mapping of visual function using the School of Biology, The Australian National pupillary response University, Canberra, ACT Ms Tiffany Cripps Eccles Institute of Neuroscience seminar, Sequencing Trouble-shooting The John Curtin School of Medical Dr Adam Cook CSIRO PIant Industry, Canberra, ACT Research, The Australian National A specific function for the histone University, Canberra, ACT chaperone NASP to fine-tune a reservoir of soluble H3-H4 in the histone supply Dr Stephen Daley Dr Marco Casarotto chain Helios marks strongly self-reactive CD4+ Design and Development of Drugs that Lorne Genome Conference, Lorne, VIC cells in two major waves of thymic Target Virus Ion Channels deletion distinguished by induction of PD-1 or NF-kappaB 56th Annual Meeting of the Biophysical Associate Professor Society, San Diego, CA, US Matthew Cook ThymUS International Conference, Sunny Isles Beach, FL, US Therapeutic Design: Targets, Strategies Effector T cells in health and disease and New Molecules The Royal College of Pathologists of Dr Vincent Daria Department of Chemistry, University of Australasia Pathology Update, Sydney, Wollongong, Wollongong, NSW NSW Patterned illumination for analysing neuronal function in 3D Immunological tolerance Dr Geeta Chaudhri Photonics Europe, Brussels, Belgium 18th Annual ICPMR Immunology The role of tumour necrosis factor in the Workshop, The Royal College of Efficient holographic photostimulation of host response to poxvirus infection Pathologists of Australasia, Westmead neurons with wavefront correction Hospital, Westmead, NSW XIX International Poxvirus, Asfarvirus and 20th Australian Institute of Physics Iridovirus Conference, Salamanca, Spain Stepping stones: CD4 T cells in human Congress, Sydney, NSW pathophysiology Advancing neurophotonics with 3D light Dr Julian Choy Menzies Institute for Medical Research, fields Hobart, TAS Technical University of Denmark, Lyngby, α1-adrenergic action in pairs of pyramidal Denmark neurons in layer II/III of rat somatosensory Follicular helper T cells cortex Australasian Rheumatology Congress, Dynamic microscopy: Using 3D light fields for stimulating synapses 33rd Annual Meeting of the Australasian Canberra, ACT Neuroscience Society, Gold Coast, QLD Immunology investigations Biocenter - Ludwig Maximilian University, Munich, Germany Deltamed Medical Investigations Course for Trainee Physicians, Melbourne, VIC

Annual Review 2012 107 Dr Debjani Das Mutations in the intramembrane IgD and Mechanisms for acquiring self- endopeptidase SPPL2A affect humoral nonself discrimination Cognition in middle-age and ADHD immunity and B-cell survival by reducing symptoms: A population-based study Centenary Institute of Cancer Medicine surface BCR and BAFF-R expression and and Cell Biology, Sydney, NSW Cognitive Aging Conference, Atlanta, GA, affecting CD74 metabolism Chris Parish: Chemistry and immunology US 15th Biennial Meeting of the European Society for Immunodeficiencies, Florence, Symposium: Chris Parish ASI life Dr Michael Dobbie Italy membership: A celebration, The John Curtin School of Medical Research, The Phenomics - Translation Through Mouse Australian National University, Canberra, Models of Human Disease Professor Chris C Goodnow ACT Masters of Translational Medicine Invited Robust systems and complex diseases: presentation, The John Curtin School of the effects of single and combined Professor Jill E Gready Medical Research, The Australian National mutations on immunological self- University, Canberra, ACT tolerance and immunity Keynote presentation: Potential contribution of advances in Center for Genetics of Host Defense, UT photosynthesis to plant productivity and Professor Angela Dulhunty Southwestern Medical Center, Dallas, TX, global food production US Interactions between the isolated DHPR Workshop on future challenges in food Dysregulation of self-tolerance β1a subunit and the Type 1 Ryanodine and agriculture: Science informing policy, Receptor checkpoints by mutations in the antigen Crawford School of Public Policy, The receptor - NFkB signaling pathway 56th Annual Meeting of the Biophysical Australian National University, Canberra, Society, San Diego, CA, US Keystone Symposium: Regulation of ACT Lymphocyte Signaling, Keystone, CO, DHPR: role in EC coupling US CARD11 lymphoma mutations switch Dr Rebecca Haddock Gage Conference on Muscle, Canberra, self-antigen induced B cell death into ACT growth NGF synthesis by inflammatory cells promotes sympathetic hyperinnervation Functional analysis of a cluster of Central Keystone Symposium: NF-kappaB in obesity Core Disease mutations reveals a gating Signaling and Biology: From Bench to module within TM6 of RyR1 Bedside, Whistler, BC, Canada 24th Scientific Meeting of the International Society of Hypertension, Sydney, NSW Combined conference of the Australian Exome sequencing and forward genetic Physiological Society, the Physiological analysis of adaptive immunity Obesity promotes vascular sympathetic Society of New Zealand, and the hyperinnervation associated with oxidative Australian Society for Biophysics, The EMBO/EMBL Symposia: New stress and inflammation University of New South Wales, Sydney, perspectives on immunity to infection, Heidelberg, Germany 24th Scientific Meeting of the International NSW Society of Hypertension Satellite Meeting: Ryanodine receptor calcium release Forward genetic analysis of adaptive Neuropathophysiology of Hypertension, channels in health and in disease immunity and memory Cairns, QLD (neuropathies, and skeletal and cardiac National Institutes of Health, Bethesda, Neuropathophysiology of obesity-related myopathies MD, US hypertension The Health Innovations Research Institute, Genetic analysis of a somatically acquired Department of Pharmacology, Monash RMIT University, Melbourne, VIC trait: immunological self-tolerance University, Melbourne, VIC NIHR Cambridge Biomedical Research What do obesity and cardiovascular Dr Anselm Enders Centre, Cambridge University, Cambridge, disease mean for modern society – are UK Finding new immune regulatory genes by we now entering ‘Generation Risk’? ENU mutagenesis Genetic analysis of a somatically acquired Invited Guest Speaker: University of the trait: immunological self-tolerance 7th European Workshop on Immune 3rd Age, Canberra, ACT Mediated Inflammatory Diseases, St Vincent’s Institute of Medical Research, Sympathetic Hyperactivity: a major Noordwijk aan Zee, The Netherlands Melbourne, VIC determinant of cardiovascular disease B-cell survival, surface BCR and BAFF-R Genetic analysis of a somatically acquired The John Curtin School of Medical expression, CD74 metabolism and trait: immunological self-tolerance Research Director’s Health through CD8- DCs require the intramembrane Garvan Institute of Medical Research, Discovery Public Lecture Series, The endopeptidase SPPL2A Sydney, NSW Australian National University, Canberra, 42nd Annual Scientific Meeting of the ACT Australasian Society for Immunology, Melbourne, VIC

108 The John Curtin School of Medical Research Mrs Angela Higgins Associate Professor Guna Publishing in High Impact Psychiatry Journals: An Editor’s Insight Sequencing Trouble-shooting Karupiah University of Lisbon, Lisbon, Portugal CSIRO PIant Industry, Canberra, ACT Mechanisms of protection from infection Pharmacogenomics: Off to Tangible XIX International Poxvirus, Asfarvirus and Success in the 21st Century Professor Caryl Hill Iridovirus Conference, Salamanca, Spain ScientificS ymposium: Longitudinal Tudor Griffith, gap junctions Remembering Frank Fenner Psychosis Research, Göttingen, Germany and conducted vasodilatation: XIX International Poxvirus, Asfarvirus and Pharmacogenetics and Antidepressant electromechanical coupling back in the Iridovirus Conference, Salamanca, Spain Treatment limelight Effector mechanisms of antiviral CD8 T International Society for Affective Plenary lecture: EDHF2012, Paris, France cells Disorders (ISAD) 6th Biennial Conference, The contribution of T-type calcium FIMSA/ IUIS/ IIS 8th Advanced Course on London, UK channels to vascular tone is increased by Basic and Translational Immunology, New Welcome Address oxidative stress Delhi, India The Australian National University Office of Invited speaker: 2nd Joint Meeting of the Is recall adaptive immunity sufficient for Commercialisation: External Engagement British and American Microcirculation recovery from secondary viral infections? and its Opportunities for the ANU Life Societies, Oxford, UK 5th Congress of Federation of the Sciences, The Australian National Immunological Societies of Asia Oceania University, Canberra, ACT Dr Lauren Howitt (FIMSA), New Delhi, India Panellist: ABC Futures Forum: How Will Increased reactive oxygen species Science Shape What it Means to be and reduced nitric oxide bioavailability Professor Trevor Lamb Human? increase the involvement of T-type Transduction and adaptation in vertebrate Canberra, ACT calcium channels to vascular tone photoreceptors Re-conceptualising Depression: What are The Australian Society for Medical Cellular Mechanisms of Sensory Today’s Most Promising Research Leads? Research ACT New Investigators Forum, Processing, Göttingen, Germany Where will the Next Breakthroughs Come Canberra, ACT From? Evolution of vertebrate photoreceptors Reduced nitric oxide bioavailability and and transduction The Royal Australian & New Zealand increased reactive oxygen species College of Psychiatrists Congress Hobart, increase the contribution of T-type Cellular Mechanisms of Sensory TAS calcium channels to vascular tone Processing, Göttingen, Germany Genetic Causes of Obesity Eccles Institute of Neuroscience seminar, Evolution of the vertebrate retina and The Royal Australian & New Zealand The John Curtin School of Medical photoreceptors College of Psychiatrists Congress Hobart, Research, The Australian National XX Biennial Meeting of the International TAS University, Canberra, ACT Society for Eye Research, Berlin, Germany Depression, Obesity and Their Interface: Mr Cameron Jack Translational Approaches Professor Julio Licinio Queensland Institute of Medical Research, ChIP-Seq Processing and Analysis Brisbane, QLD Workshop: Bioinformatics for High Translational Approaches to the Shared The interface of obesity and depression Throughput Sequencing, The John Curtin Biology of Stress, Depression, and School of Medical Research/ Research Obesity School of Biomedical Sciences, Monash University, Melbourne, VIC School of Biology, The Australian National 25th Annual International Symposium of University, Canberra, ACT the Centre for Study of Gene Structure & Genetics and Translational Research at Exploring the Relationship between Function: The Stressed Brain in the 21st the Depression - Obesity Interface chromatin and expression with ChipPy Century: Research Advances & Clinical University of Texas Medical Centre, Dimensions Hunter College, New York, Techniques in Computational Genomics, Dallas, TX, US NY, US Research School of Biology, The Obesity as a Medical Outcome of Australian National University, Canberra, Major Depression: From Clinical Depression and Antidepressant Treatment ACT Syndrome to Biological Candidates, 13th International Mental Health Genetics and Pharmacogenomics Conference, Surfer’s Paradise, QLD University of Lisbon, Lisbon, Portugal Obesity and Depression Cardinal Bioresearch Pty Ltd Obesity / Gut Hormone Workshop, Gold Coast, QLD

Annual Review 2012 109 Obesity, Depression and Stress The Application of Pattern Recognition Clinical utility of multifocal pupillographic 10th International Catecholamine and Knowledge Discovery as a Basis objective perimetry in Type 1 diabetes Symposium Asilomar Conference, Pacific for Alternative Systems and Methods in Australian Ophthalmic and Visual Grove, CA, US Fundamental Biomedical Research Sciences Meeting, Melbourne, VIC Introduction to Molecular Neuropsychiatry Invited seminar: The Griffith Health Diagnostic accuracy of multifocal and its Role in Child Adolescent Mental Institute, Griffith University, Gold Coast, pupillographic objective perimetry Health QLD (mfPOP) in early age-related macular The Royal Australian and New Zealand Non-Animal Alternatives for Biomedical degeneration College of Psychiatrists’ Faculty of Child Research Australian Ophthalmic and Visual and Adolescent Psychiatry Conference, Invited speaker: Introduction to Animal Sciences Meeting, Melbourne, VIC Sydney, NSW Research, University of Sydney, Sydney, Daily variations in spectral domain OCT Translational Psychiatry: How can NSW measurements Pharmacogenomics Bridge the Australian Ophthalmic and Visual Translational Gap in Mental Health? Dr Fiona Lithander Sciences Meeting, Melbourne, VIC Creighton University, Omaha, NE, US Postprandial response of adiponectin, SAP undersampling and test–retest New Approaches to the Treatment of tumour necrosis factor-α and interleukin-6 variability to a high-carbohydrate meal in liquid Depression ANZ Glaucoma Interest Group, Sydney, versus solid form Abu Dhabi Health Services, Abu Dhabi, NSW European Congress on Obesity, Liverpool, UAE Relative effects of sampling errors and UK Translational research on obesity and eye movements upon SAP test–retest depression NOURISH Irish-Ugandan Research variablity Cluster; the nutrition component Brain and Mind Research Institute Imaging and Perimetry Society, Psychosis Australia Research Meeting, Kings College London, London, UK Melbourne, VIC Sydney, NSW The link between obesity and Improving multifocal objective The critical interface with depression and inflammation; can diet help? pupillographic perimetry for glaucoma antidepressant treatment University of Canberra, Bruce, ACT American Academy of Ophthalmology, Obesity Australia Summit, Canberra, ACT Chicago, IL, US Professor Ted Maddess Associate Professor Brett Targeting melanopsin with mfPOP: Dr Claudio A Mastronardi Lidbury Blue multifocal pupillographic objective Neuroimmunomodulation perimetry in glaucoma 1R at the ANU – Mission, Research Translational Medicine Pathways - Master Strategy and a National Centre (ACAAR) The Association for Research in Vision of Translational Medicine Coursework and Ophthalmology Meeting, Fort Invited seminar: Swedish Fund for Program, The Australian National Lauderdale, FL, US Research Without Animal Experiments, University, Canberra, ACT Stockholm, Sweden SAP undersampling and test–retest Possible interactions between variablity Pattern Recognition and Knowledge immunoendocrine elements and Major Discovery Informatics as a Basis for The Association for Research in Vision Depression Animal Replacement in Biomedical and Ophthalmology Meeting, Fort Centre for Pharmacological and Botanical Research and Toxicology - Two Elevated Lauderdale, FL, US Studies, School of Medicine of the Gamma Glutamyl Transferase (GGT) Comparison of macular and widefield University of Buenos Aires, Buenos Aires Scenarios multifocal pupillographic objective City, Argentina European Society for Toxicology In Vitro perimetry in patients with diabetes (ESTIV) 2012 Meeting, Lisbon, Portugal The Association for Research in Vision Dr Riccardo Natoli The Application of Pattern Recognition and Ophthalmology Meeting, Fort A novel preventative strategy for and Knowledge Discovery as a Basis Lauderdale, FL, US retinopathy of prematurity for Alternative Systems and Methods in It’s not what you show, it’s the way Fundamental Biomedical Research XX Biennial Meeting of the International that you show it: Stimulus presentation Society for Eye Research, Berlin, Invited seminar: The Therapeutic Goods variants for multifocal pupil perimetry in Germany Administration (TGA), Symonston, ACT glaucoma. Australian Ophthalmic and Visual Sciences Meeting, Melbourne, VIC

110 The John Curtin School of Medical Research Dr Teresa Neeman Professor Christopher R Dr Åsa Pérez-Bercoff Statistical issues in clinical trials Parish Funtion and evolution of genes in the Masters of Translational Medicine Invited The role of platelets in tumour metastasis human protein interaction network presentation, The John Curtin School of Perth Cancer Club, Perth, WA TIC seminar, The John Curtin School of Medical Research, The Australian National Medical Research, The Australian National University, Canberra, ACT New insights into Type 1 diabetes University, Canberra, ACT development and therapy Statistical thinking in biological research Western Australia Institute of Medical Dr Jason Potas Invited Presentation to PhD students, The Research, Perth, WA John Curtin School of Medical Research, Treatment with 670 nm (red) The Australian National University, photobiomodulation following sciatic Canberra, ACT Dr Hardip Patel nerve injury promotes functional An introduction to multiple hypothesis Human RNA-methylome: A Novel Layer improvements associated with reduced testing of RNA Regulation macrophage recruitment TIC seminar, The John Curtin School of Genetics Society of AustralAsia Annual 33rd Annual Meeting of the Australasian Medical Research, The Australian National Meeting, Melbourne, VIC Neuroscience Society, Gold Coast, QLD University, Canberra, ACT RNAseq: Data analysis and applications Workshop: Bioinformatics for High Professor Thomas Preiss Dr Maxim Nekrasov Throughput Sequencing, The John Curtin Mechanisms and patterns of eukaryotic Histone variant H2A.Z progression School of Medical Research/ Research post-transcriptional gene control School of Biology, The Australian National through the cell cycle and its influence on 7th International Conference on University, Canberra, ACT promoter structure Genomics & Bio-IT APAC, Hong Kong ComBio, Adelaide, SA Sex chromosome dosage compensation China in snakes Widespread occurrence of Dr Nicole Norris ComBio, Adelaide, SA 5-methylcytosine in human coding and Genome Discovery Unit: GainiNG Data non-coding RNA 17th Annual Meeting of Targeting lysine-specific histone Usability the RNA Society, Ann Arbor, MI, US demethylases for anti-cancer drugs Bioinformatics Microsymposium, Mechanisms and patterns of eukaryotic Invited speaker: Epigenomics in the Research School of Biology, The post-transcriptional gene control Capital Symposium, Canberra, ACT Australian National University, Canberra, International Meeting GRK 1591: ACT Posttranscriptional Control of Gene Dr Ian Parish Expression – Mechanisms and Role in Pathogenesis, Halle, Germany Effector T cells self-regulate during Dr Gilberto Paz Filho chronic viral infection by IL-10 over- Fat and the brain – interactions between production Professor Jan Provis obesity, appetite and mood Department of Microbiology and An hypothesis about macular Neuroendocrinology Australasia- Immunology, University of Melbourne, degeneration Endocrine Society of Australia, Brisbane, Melbourne, VIC QLD Vision Down Under: O’Reilly’s Rainforest Blimp-1 triggers the formation of Retreat, Lamington National Park, QLD The Genetics of Obesity immunoregulatory IL-10 producing Th1 Complement activation in an animal cells during chronic viral infection Paediatrics Grand Rounds Presentation, model of dry AM The Canberra Hospital, Canberra, ACT ACT and NSW Australasian Society of XX Biennial Meeting of the International Immunology Branch Retreat, Bowral, Adipose tissue transplantation improves Society for Eye Research, Berlin, NSW metabolic, behavioural and histological Germany parameters in leptin-deficient mice Blimp-1 triggers the formation of immunoregulatory IL-10 producing Th1 94th Endocrine Society Annual Meeting, cells during chronic viral infection Houston, TX, US 42nd Annual Scientific Meeting of the Endocrine research in Brazil and Turkey Australasian Society for Immunology, The 3rd Bootes Course on Translational Melbourne, VIC Medicine: The Pathway from Discovery to Healthcare, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT

Annual Review 2012 111 Dr Charani Ranasinghe Mr Stuart Read Dr Charmaine Simeonovic Flow cytometry analysis of T cells in HIV Mouse strain cryopreservation in Australia Diminished heparan sulfate levels in vaccine development European Mouse Mutant Archive & human beta cells represent a fundamental The University of Technology, Sydney, International Society of Transgenic defect in Type 1 and Type 2 diabetes and NSW Technologies Workshop, Madrid, Spain lead to beta cell death Vaccination regimes that promote 12th International Conference on the strong mucosal T cell immunity: Role of Dr Matt Rutar Immunology of Diabetes, Victoria, Canada Interferon epsilon Loss of beta cell heparan sulfate and Complement activation in an animal expression of heparanase by insulitis International Microbicide Conference model of dry AMD workshop, Sydney, NSW mononuclear cells correlate with Type 1 XX Biennial Meeting of the International diabetes in human pancreas specimens Mucosal HIV-1 vaccines: Taking a vaccine Society for Eye Research, Berlin, nPOD 4th Annual Meeting, Miami, FL, US from bench to a clinical trial Germany Heparan sulfate and heparanase play BioPharma Sydney Conference, Sydney, Near-infrared treatment reduces NSW critical roles in islet beta cell health and complement propagation in a light- Type 1 diabetes HIV/AIDS and Mucosal Vaccines induced model of atrophic AMD Invited Symposium speaker: Annual The 3rd Bootes Course on Translational XX Biennial Meeting of the International Medicine: The Pathway from Discovery Scientific Meeting of the Bosch Institute, Society for Eye Research, Berlin, University of Sydney, Sydney, NSW to Healthcare, The John Curtin School of Germany Medical Research, The Australian National Annual Scientific Meeting of the Bosch University, Canberra, ACT Near-infrared treatment reduces Institute, University of Sydney, Sydney, complement propagation in a light- NSW Novel vaccine strategies that modulate induced model of atrophic AMD HIV-specific CD8 T cell avidity Beta cell heparan sulfate: a critical XV International Symposium on Retinal biomarker for Type 1 and Type 2 diabetes Australian Centre for Hepatitis and HIV Degeneration, Bad Gögging, Germany Virology (ACH2), Adelaide, SA 5th Australian Islet Study Group (AISG) Role of chemokine immune response Meeting, Melbourne, VIC Vaccines: Pitfalls Bottle-necks and future pathways in a light-induced degenerative prospects Loss of beta cell heparan sulfate (HS) model of atrophic AMD and expression of heparanase by insulitis The John Curtin School of Medical Australian Ophthalmic and Visual mononuclear cells (MNCs) correlates with Research Director’s Health through Sciences Meeting, Melbourne, VIC Type 1 diabetes (T1D) in human pancreas Discovery Public Lecture Series, The specimens Australian National University, Canberra, ACT Dr Faran Sabeti Annual Scientific Meeting of the Australian Diabetes Society and the Australian Promising HIV-1 vaccine strategies to Comparison of macular and widefield Diabetes Educators Association, Gold enhance mucosal immunity and CD8+ T multifocal pupillographic objective Coast, QLD cell avidity perimetry in patients with diabetes Type 1 diabetes: Prospects for a new Australian Society for HIV Medicine The Association for Research in Vision therapy (ASHM), Melbourne, VIC and Ophthalmology Meeting, Fort Lauderdale, FL, US Inaugural Lecture: The John Curtin School of Medical Research Director’s Dr Katrina L Randall Clinical utility of multifocal pupillographic Health through Discovery Public Lecture objective perimetry in Type 1 diabetes Series, The Australian National University, Memory B cells in DOCK8 deficiency Australian Ophthalmic and Visual Canberra, ACT ACT and NSW Australasian Society of Sciences Meeting, Melbourne, VIC Novel roles for heparan sulfate and Immunology Branch Retreat, Bowral, heparanase in Type 1 diabetes NSW Diagnostic accuracy of multifocal pupillographic objective perimetry Symposium: Chris Parish ASI life DOCK8 deficiency cripples CD8 T cells in (mfPOP) in early age-related macular membership: A celebration, The John humans and mice degeneration Curtin School of Medical Research, The FOCIS 2012, Vancouver, Canada Australian Ophthalmic and Visual Australian National University, Canberra, DOCK8 Immunodeficiency –lessons learnt Sciences Meeting, Melbourne, VIC ACT from the mice Award Seminar: Frank Fenner Medal and Dewar Milne Prize in Immunology, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT

112 The John Curtin School of Medical Research Dr Tanya Soboleva Dr Rebecca Sweet The link between chromatin structure and function during early development A new player in a fundamental male Autoreactive B Cell Memory Leads to game: Gene activation by a novel histone Rapid, Switched, Antibody Forming Cell Peter MacCallum Cancer Institute, variant during mouse spermiogenesis Responses Melbourne, VIC Invited speaker: The Annual Scientific ACT and NSW Australasian Society of The link between chromatin structure and Meeting of the Endocrine Society of Immunology Branch Retreat, Bowral, function during early development Australia and the Society for Reproductive NSW Department of Biochemistry & Molecular Biology, Gold Coast, QLD B cell extrinsic MyD88 and FcR common Biology, Monash University, Melbourne, A unique H2A histone variant occupies gamma chain control contraction of the VIC the transcriptional start site of active autoreactive extrafollicular B cell response The role of histone variants in regulating genes 42nd Annual Scientific Meeting of the differentiation and development Invited speaker: ComBio, Adelaide, SA Australasian Society for Immunology, Murdoch Children’s Medical Research Gene activation by a novel histone variant Melbourne, VIC Institute, Melbourne, VIC during mouse spermatogenesis Invited speaker: Epigenomics in the Dr Charis Teh Dr Krisztina Valter Capital Symposium, University of Identifying and tracking T cells that drive Oxygen-induced retinal changes – from Canberra, Bruce, ACT spontaneous autoimmune pancreatitis mechanism to treatment 42nd Annual Scientific Meeting, Invited symposium presentation: XX Professor Greg Stuart Australasian Society for Immunology, Biennial Meeting of the International Electrical properties of dendritic spines Melbourne, VIC Society for Eye Research, Berlin, Germany Dendrites: Substrates for Information Double layered armour protects the body Processing, Howard Hughes Medical from friendly fire The new anatomy laboratory Institute Janelia Farm research Campus, BD Science Communication: 42nd Joint meeting of the Australian and Ashburn, VA, US Annual Scientific Meeting, Australasian New Zealand Association of Clinical Na+ channels in the axon initial segment Society for Immunology, Melbourne, VIC Anatomists and the Australasian Institute and their role in action potential Multi-layered armour protects the body of Anatomical Sciences, Sydney, NSW generation from friendly fire Does contextualization aid the study 8th Federation of European Neuroscience The John Curtin School of Medical of musculoskeletal anatomy in an Societies Forum of Neuroscience, Research Director’s Health through undergraduate biomedical course? Barcelona, Spain Discovery Public Lecture Series, The Joint meeting of the Australian and Electrical properties of dendritic spines Australian National University, Canberra, New Zealand Association of Clinical ACT Anatomists and the Australasian Institute Developments in Imaging Symposium, of Anatomical Sciences, Sydney, NSW QBI, The University fo Queensland, Brisbane, QLD Professor David Tremethick A new therapeutic approach in the prevention of retinopathy of prematurity H2A.Z inheritance during the cell cycle Dendritic integration in cortical pyramidal (Egy új lehetséges nem-invazív therápia a and its impact on promoter organisation neurons ROP megelőzésére) and dynamics Keynote speaker: 10th Dutch Endo- Congress of the Hungarian Gordon Conference on Chromatin Neuro-Psycho meeting, Lunteren, The Ophthalmological Society, Siofok, Structure and Function, Lucca (Barga), Netherlands Hungary Italy Studying synaptic integration in the intact Retinal degenerations: processes and H2A.Z inheritance during the cell cycle brain treatments and its impact on promoter organisation The Florey Institute of Neuroscience and and dynamics Invited Seminar: University of L’Aquila, Mental Health, Melbourne, VIC L’Aquila, Italy Cold Spring Harbor Laboratories meeting on Epigenetics and Chromatin, Cold Implementation of eLearning in anatomy: Dr Norimitsu Suzuki Spring Harbor, NY, US key factors for success Persistent firing in neurogliaform cells: An A unique H2A histone variant occupies Joint meeting of the Australian and endogenous mechanism for suppressing the transcriptional start site of active New Zealand Association of Clinical seizures? genes Anatomists and the Australasian Institute of Anatomical Sciences, Sydney, NSW 33rd Annual Meeting of the Australasian Lorne Genome Conference, Lorne, VIC Neuroscience Society, Gold Coast, QLD

Annual Review 2012 113 Professor Carola G Vinuesa Professor Ma-Li Wong Translational Research: Obesity, depression and their interface as case FoxP3+ Regulatory T Cells and NKT Cells Pharmacogenomics examples Co-Opt the Tfh Differentiation Pathway Clinical Pharmacological Tutorial, Master to Upregulate CXCR5 and Become Medicine Rounds, National University of of Translational Medicine Coursework Singapore, Singapore Specialized T Follicular Regulatory or Program, The Australian National Helper Cells University, Canberra, ACT Biological basis of schizophrenia Chemokines and Leukocyte Trafficking Major Depression: A Common Complex ANU Medical School, The Australian in Homeostasis and Inflammation, Disorder National University, Canberra, ACT Breckenridge, CO, US Academic Unit of Psychiatry & Addiction Pharmacogenomics Follicular T Helper Cells: Crucial Players in Medicine, Canberra, Australia Clinical Pharmacological Tutorial, Master Driving Somatic Hypermutation during an of Translational Medicine Coursework Antibody Response Overview of Translation and Introduction to Course Program, The Australian National 19th Conference on Retroviruses and University, Canberra, ACT Opportunistic Infections, Seattle, WA, US The 3rd Bootes Course on Translational Medicine: The Pathway from Discovery The role of immunomediators in Follicular helper, Follicular regulatory and to Healthcare, The John Curtin School of depression Follicular NK T cells Medical Research, The Australian National Academic Forum, The University of New Gordon Research Conference on University, Canberra, ACT South Wales, Sydney, NSW Antibody Biology and Engineering, The role of leptin in the Galveston, TX, US pharmacogenomics of obesity Professor Ian Young Cellular and molecular regulation of Pharmacogenomics and personalized antibody responses Cytokine-stimulated differentiation of medicine in psychiatry: Prospects for granulocytes & macrophages: targeting Women in Science Lecture, The Walter clinical implementation, The International microRNAs in allergic inflammation and Eliza Hall Institute of Medical College of Neuropsychopharmacology Research, Melbourne, VIC Stockholm, Sweden Invited Lecture: School of Life Sciences, The Chinese University of Hong Kong, Novel layers of regulation of helper T cells The Foundation of Translational Medicine Hong Kong in germinal centers and Co-Chair International Forum on New Advances in China Tregs/TH Subsets Conference, The 3rd Bootes Course on Translational Life Sciences Shanghai, China Medicine: The Pathway from Discovery to Healthcare, The John Curtin School of Keynote Speaker: Fujian Medical Insights into cells and genes that prevent University, Fuzhou, China autoantibody formation in mice and Medical Research, The Australian National humans University, Canberra, ACT Symposium, The Walter and Eliza Hall From Clinical Research to Clinical Care: Institute of Medical Research, Melbourne, Outcomes of Translational Research on VIC healthcare practice, guidelines and policy The 3rd Bootes Course on Translational Associate Professor Hilary Medicine: The Pathway from Discovery to Healthcare, The John Curtin School of Warren Medical Research, The Australian National Cellular assays to assess Natural Killer cell University, Canberra, ACT function in patients Pharmacogenomics of depression: Symposium speaker: 36th Asia-Pacific Pathways and mechanisms Histocompatibility and Immunogenetics Queensland Institute of Medical Research, Association Meeting, Adelaide, SA Brisbane, QLD Unraveling the biology and medical complications of depression: From endocrine and metabolic effects to genomic science Research Meeting at Department of Psychological Medicine, National University of Singapore, Singapore

114 The John Curtin School of Medical Research Student Presentations

Z Al Rumaih AYH Chain The role of heparanase in the rejection of islet allografts The protective role of TNF in recovery Multifocal pupillographic perimetry from poxvirus infection and ocular coherence tomography 5th Australian Islet Study Group (AISG) Meeting, Melbourne, VIC 42nd Annual Scientific Meeting, measurements in glaucoma Australasian Society for Immunology, Australian Ophthalmic and Visual Melbourne, VIC Sciences Meeting (AOVSM), Melbourne, P Eldi Australia Role of CD4 T cells in recovery from RS Albarracin secondary poxvirus infections S-Y Chan Effects of 670 nm light on the blood– 42nd Annual Scientific Meeting, retinal barrier of a murine model of DOCK8 deficiency impairs CD8 T cell Australasian Society for Immunology, oxygen-induced model of retinal survival and function in humans and mice Melbourne, VIC degeneration Keystone Symposia Global Health Role of CD4 T cells in recovery from XX Biennial Meeting of the International Series: Immunological mechanisms of secondary poxvirus infections Society for Eye Research, Berlin, vaccination, Ottawa, ON, Canada Infection and Immunity Special Interest Germany DOCK8 deficiency impairs CD8 T cell Group, 42nd Annual Scientific Meeting, Dysregulation of the outer blood–retinal survival and function in humans and mice Australasian Society for Immunology, Melbourne, VIC barrier in hyperoxic mice is regulated by Department of Immunology, The 670 nm light pretreatment University of Toronto, ON, Canada BP Gang, PJ Dilda, PJ Hogg XX Biennial Meeting of the International DOCK8 deficiency impairs CD8 T cell Society for Eye Research, Berlin, survival and function in humans and mice and AC Blackburn Germany Emory Vaccine Center, Emory University, Dichloroacetate reverses the Warburg Atlanta, GA, US effect, inhibiting growth and sensitizing H Bergmann breast cancer cells towards apoptosis An essential protease for B cells and DCs D Chaston American Association for Cancer Research Annual Meeting, Chicago, IL, US NHMRC Program Grant Meeting, The Chronic impairment of endothelial Australian National University Kioloa connexin40 enhances vasoconstriction Coastal Campus, Kioloa, NSW and arterial stiffening M Go B-cell survival, surface BCR and BAFF-R Australian Society of Medical Research Simultaneous multi-site nonlinear expression, CD74 metabolism and New Investigator Forum, Canberra, ACT photostimulation in 3D CD8- DCs require the intramembrane endopeptidase SPPL2A Chronic impairment of endothelial 33rd Annual Meeting of the Australasian connexin40 enhances vasoconstriction Neuroscience Society, Gold Coast, QLD ACT and NSW Australasian Society of and arterial stiffening Immunology Branch Retreat, Bowral, Simultaneous 3D multi-site uncaging of NSW Canberra Health Annual Research neurotransmitter to study neuronal signal Meeting, The Canberra Hospital, integration The intramembrane endopeptidase Canberra, ACT SPPL2A is required for dendritic cell The Annual Kioloa Neuroscience development and CD74 metabolism Chronic impairment of endothelial Colloquium, Kioloa Coastal Campus, connexin40 enhances arterial constriction The Australian National University, Kioloa, 42nd Annual Scientific Meeting of the and reduces arterial distensibility NSW Australasian Society for Immunology, Melbourne, VIC 24th Scientific Meeting of the International 3D holographic photostimulator and Society for Hypertension, New optical scalpel for manipulating neurons Investigator Symposium, The University of H Bock Eccles Institute of Neuroscience Seminar Sydney, Sydney, NSW Series, The John Curtin School of Medical SK channels enhance dendritic excitability Research, Canberra, ACT of cortical layer 5 pyramidal neurons FJ Choong 33rd Annual Meeting of the Australasian The role of heparanase in the rejection of AD Hanna, AF Dulhunty and Neuroscience Society, Gold Coast, QLD islet allografts NA Beard The role of calcium activated potassium 30th Annual Scientific Meeting, channels in the modulation of dendritic Multiple effects of anthracyclines on the Transplantation Society of Australia and cardiac ryanodine receptor excitability New Zealand, Canberra, ACT The Annual Kioloa Neuroscience The 2012 Gage Conference on Muscle: Colloquium, Kioloa Coastal Campus, Excitation-Contraction Coupling, The Australian National University, Kioloa, Canberra, ACT NSW

Annual Review 2012 115 AD Hanna, AF Dulhunty and CJ Hynes Interferon-gamma excess lead to accumulation of pathogenic follicular NA Beard The tell-tail heart: miRNA variants and helper T cells and germinal centers 3’UTRs in cardiac hypertrophy Anthracycline-induced dysfunction of Winter School on Advanced Immunology, cardiac SR Ca2+ handling: a potential ComBio, Adelaide, SA Kobe, Japan pathway to anthracycline-induced A tail of the heart: miRNAs and 3’UTRs in cardiotoxicity cardiac hypertrophy L Li, NA Beard NA and AF Gordon Conference on Muscle: Excitation Australian Society of Medical Research Contraction Coupling, Les Diablerets, Dulhunty New Investigator Forum, Canberra, ACT Switzerland In vitro characterization of interactions CJ Hynes, DT Humphreys, JL between junctin and ryanodine receptor AD Hanna, A Lam, AF (RyR1/ RyR2) Clancy, HR Patel, C Suter and Dulhunty and NA Beard Gordon Research Conference on Muscle T Preiss Excitation-Contraction Coupling, Les Anthracycline-induced dysfunction of Diablerets, Switzerland cardiac SR Ca2+ handling: A potential The role of miRNA variants and alternative pathway to anthracycline-induced polyadenylation in cardiac hypertrophy cardiotoxicity 33rd Annual Lorne Genome Conference, L Li, NA Beard and AF The Australian Physiological Society, Lorne, VIC Dulhunty Sydney, NSW Characterization of interactions between S Jones junctin and ryanodine receptor (RyR1/ RyR2) in vitro S Hausner Different calcium sources control somatic The effect of training, altitude exposure and dendritic SK channel activation in The 2012 Gage Conference on Muscle: and an athlete’s sex on expression cortical pyramidal neurons Excitation-Contraction Coupling, Canberra, ACT of genes known to change following 8th Federation of European Neuroscience autologous blood transfusion Societies Forum on Neuroscience, Biomarker Discovery Conference, Shoal Barcelona, Spain A Mishra, AC Blackburn, C Bay, NSW Activation of SK channels in spines and Parish, M Wong and J Licinio dendrites by action potentials Leptin increases metastatic potential of JF Heffernan, K Valter and J 33rd Annual Meeting of the Australasian breast cancer cells Neuroscience Society, Gold Coast, QLD Potas 24th Lorne Cancer Conference, Lorne, Treatment with 670 nm (red) VIC photobiomodulation following sciatic M Kolic nerve injury promotes functional mfPOP fields with higher density white A Mohan improvements associated with reduced and yellow stimuli macrophage recruitment Functional relevance and physiological Australian Ophthalmic and Visual basis of target-specific synaptic plasticity 33rd Annual Meeting of the Australasian Sciences Meeting (AOVSM), Melbourne, in the layer IV excitatory circuit Neuroscience Society, Gold Coast, QLD Australia 33rd Annual Meeting of the Australasian Effect of intra-ocular lenses on diagnostic Neuroscience Society, Gold Coast, QLD H Huang performance of mfPOP in glaucoma Short-term synaptic depression and Functional differences between two 20th International Visual Field and Imaging neuronal spiking dynamics together tune classes of layer 2 principal neurons in the Symposium, Melbourne, Australia integration and coincidence detection pirifrom cortex in vivo properties of neurons The Annual Kioloa Neuroscience SK Lee 42nd Annual Meeting of the Society for Colloquium, Kioloa Coastal Campus, Neuroscience, New Orleans, LA, US Interferon-gamma excess lead to The Australian National University, Kioloa, accumulation of pathogenic follicular NSW helper T cells and germinal centers S Morton Functional differences between two Keystone Symposia: Mutations, classes of layer 2 principal neurons in the Interference with endothelial gap Malignancy and Memory – Antibodies and pirifrom cortex in vivo junctional coupling via connexin40 Immunity, Boston, MA, USA produces hypertension in mice Sensory Neuroscience Symposium, University of Western Sydney, 24th Scientific Meeting of the International Campbelltown, NSW Society for Hypertension, The University of Sydney, Sydney, NSW

116 The John Curtin School of Medical Research Interference with endothelial gap ROQUIN is an immunometabolic regulator J Robertson junctional coupling via connexin40 of follicular regulatory and helper T cells produces hypertension in mice Excitatory neurons in layer III of the Research Center for Allergy and primary olfactory cortex Australian Society of Medical Research Immunology (RCAI) International Summer New Investigator Forum, Canberra, ACT Program, RIKEN, Yokohama, Japan 33rd Annual Meeting of the Australasian Neuroscience Society, Gold Coast, QLD ROQUIN uncouples CD4+ T follicular S Newman regulatory VS helper cell lineage Excitatory neurons in layer III of the commitment primary olfactory cortex: classification and Darwinian fitness and the health of familial involvement in epilepsy networks 14th International Conference on Lymphocyte Activation and Immune Kioloa Neuroscience Symposium, ANU VII Congreso Internacional Cerebro y Regulation: T cell Differentiation and Coastal Campus, Kioloa, NSW Mente, Medellin, Colombia Plasticity, Newport Beach Hotel, CA, US Classification of excitatory neurons in layer III of the mouse piriform cortex E Pillai M Ratnadiwakara, R Williams International Symposium on Olfaction and The effect of lamin A/C siRNA and AC Blackburn Taste, Stockholm, Sweden knockdowns on base excision repair of 8-oxoG DNA lesions Vitamin D, CYP2R1 and breast cancer susceptibility S Rudinski Interdisciplinary Aspects of Healthy Functional characterisation of a Aging, International Alliance of Research Familial aspects of cancer: Research and channelrhodopsin-2 transgenic mouse Universities, University of Copenhagen, practice, Gold Coast, QLD Copenhagen, Denmark 33rd Annual Meeting of the Australasian Neuroscience Society, Gold Coast, QLD Quantitative linkage and association M Ratnadiwakara, M Rooke, analysis of ADHD endophenotypes to loci R Williams and AC Blackburn, Optogenetics: Switching brain cells on conferring susceptibility to ADHD and off with light Contribution of genetic variation within University of the 3rd Age Annual Health Master of Neuroscience (Research) SuprMam1 and SuprMam2 to breast Forum, Hughes, ACT Seminar, The John Curtin School of cancer susceptibility Medical Research, ANU, Canberra, ACT Optogenetics: Shedding light on neuronal 24th Lorne Cancer Conference, Lorne, signalling Phenotypic and epidemiological ADHD VIC variation attributed to sex-chromosomal University of South Australia Medical linkage Science Program, The John Curtin School RT Rebbeck, Y Karunasekara, Neuroscience Essay and Hall Research of Medical Research, Canberra, ACT Presentation Series, ANU, Canberra, ACT PG Board, MG Casarotto, NA Optogenetic tools in the study of cortical Beard and AF Dulhunty circuitry A Pratama In vitro interactions between C-terminal Eccles Institute of Neuroscience Seminar Series, The John Curtin School of Medical Overlapping functions of MNAB and residues of the DHPR β1a subunit and Research, Canberra, ACT ROQUIN in the repression of mRNAs the RyR1 controlling Tfh cell accumulation and Gordon Conference on Muscle: Excitation Optogenetics: Probing the function of systemic inflammation Contraction Coupling, Les Diablerets, distal dendrites 42nd Annual Scientific Meeting of the Switzerland The Annual Kioloa Neuroscience Australasian Society for Immunology, Colloquium, Kioloa Coastal Campus, Melbourne, VIC RT Rebbeck, Y Karunasekara, The Australian National University, Kioloa, PG Board, MG Casarotto, NA NSW R Ramiscal Beard and AF Dulhunty Z Sabouri ROQUIN inhibits Adenosine In vitro interactions between C-terminal Antibody Redemption: Removal of self- Monophosphate-activated Protein Kinase residues of the dihydropyridine receptor in germinal centre T cells reactivity from cross-reactive antibodies β1a subunit and the type 1 ryanodine by purifying selection in germinal centers 42nd Annual Scientific Meeting of the receptor ACT and NSW Australasian Society of Australasian Society for Immunology, The 2012 Gage Conference on Muscle: Immunology Branch Retreat, Bowral, Melbourne, VIC Excitation-Contraction Coupling, NSW Canberra, ACT

Annual Review 2012 117 Redemption of self-reactive antibodies M Singh J Velez by mutation and purifying selection in germinal centers Tracking autoimmune-inducing T cell A novel method for identifying genetic clones in Aire-/-Cblb-/- mice variants and its application to Alzheimer’s Research Center for Allergy and disease Immunology (RCAI) International Summer Australian Society of Medical Research Program, RIKEN, Yokohama, Japan New Investigator Forum, Canberra, ACT VII Congreso Internacional Cerebro y Mente and I Congreso Antioqueño de Antibody Redemption: Removal of self- Tracking autoimmune-inducing T cell clones in Aire-/-Cblb-/- mice Neurología y Neuropediatría Medellin, reactivity from cross-reactive antibodies Colombia by purifying selection in germinal centers ACT and NSW Australasian Society of Pruebas de Independencia Completa vía Australian Society of Medical Research Immunology Branch Retreat, Bowral, NSW FDR [Testing Complete Independence via New Investigator Forum, Canberra, ACT FDR] A Tan IX International Colloquium in Statistics: A Saikal Métodos Estadísticos Aplicados a Signal and noise in multifocal Function of viral schlafen during a Finanzas y Salud, National University of pupillographic objective perimetry poxvirus infection Colombia, Medellín, Colombia (mfPOP) in early age-related macular 42nd Annual Scientific Meeting, Estimation of Confidence Intervals in degeneration Australasian Society for Immunology, Poisson Regression Australian Ophthalmic and Visual Melbourne, VIC IX International Colloquium in Statistics: Sciences Meeting (AOVSM), Melbourne, Métodos Estadísticos Aplicados a VIC SM To Finanzas y Salud, National University of Colombia, Medellín, Colombia Modelling Binocular integration in layer C Shean 2/3 simple cells A new method for detecting significant p-values and its application to genetic Signal and noise of multifocal 33rd Annual Meeting of the Australasian data pupillographic stimulus response Neuroscience Society, Gold Coast, QLD functions IX International Colloquium in Statistics: Modelling Binocular integration in layer Métodos Estadísticos Aplicados a Australian Ophthalmic and Visual 2/3 simple cells Finanzas y Salud, National University of Sciences Meeting (AOVSM), Melbourne, The Annual Kioloa Neuroscience Colombia Medellín, Colombia VIC Colloquium, Kioloa Coastal Campus, Combinación de pruebas de hipótesis The Australian National University, Kioloa, independientes para proporciones: un T Sibbritt, DT Humphreys, JE NSW estudio de simulación [Comparison of Squires, HR Patel, M Nousch, The Role of dendritic nonlinearities in independent hypothesis for proportions: a SJ Clark and T Preiss neural information processing simulation study] Neurolunch Seminar, Flinders University, IX International Colloquium in Statistics: Investigating the function of Adelaide, South Australia. Métodos Estadísticos Aplicados a 5-methylcytosine in RNA by next- Finanzas y Salud, National University of generation sequencing Dendritic nonlinearities allow neurons Colombia at Medellín, Medellín, Colombia to encode different patterns of synaptic Australian Society of Medical Research input New Investigator Forum, Canberra, ACT 42nd Annual Meeting of the Society for DK Wijesundara Neuroscience, New Orleans, LA, US T Sibbritt, DT Humphreys, JE Enhanced interleukin-4 receptor α (IL-4Rα) expression on CD8+ T cells Squires, HR Patel, M Nousch, V Tran correlates with lower quality anti-viral SJ Clark and T Preiss immunity Lack of glutamate-mediated responses in 42nd Annual Scientific Meeting of the Investigating the function of immune cells 5-methylcytosine in RNA by next- Australasian Society for Immunology, 33rd Annual Meeting of the Australasian generation sequencing Melbourne, VIC Neuroscience Society, Gold Coast, QLD 33rd Annual Lorne Genome Conference, Lorne, VIC

118 The John Curtin School of Medical Research Dynamic regulation of Interleukin-4 E Wium, AF Dulhunty and NA receptor alpha (IL-4Ra) following viral infections and modulation of CD8+ T cell Beard avidity Identifying the Trisk95 residues that Australasian Society for HIV/AIDS activate the skeletal muscle ryanodine Medicine (ASHM) Conference, Melbourne, receptor VIC Gordon Conference on Muscle: Excitation Interleukin (IL)-4/IL-13 receptor Contraction Coupling, Les Diablerets, distribution on immune cells following Switzerland vaccinia virus infection: implications on CD8+ functional quality E Wium, AF Dulhunty and NA Australian Society of Medical Research Beard New Investigator Forum, Canberra, ACT Identifying the Trisk95 residues that activate the skeletal muscle ryanodine H Willemse, MG Casarotto, receptor PG Board, PN Smith and AF The 2012 Gage Conference on Muscle: Dulhunty Excitation-Contraction Coupling, Canberra, ACT Possible effects of aging on interactions between the DHPR and RyR1 in human skeletal muscle Y Xi, SL Day, RJ Jackson and The 2012 Gage Conference on Muscle: C Ranasinghe Excitation-Contraction Coupling, Role of novel type I interferon Epsilon Canberra, ACT (IFN-e) in viral infection and mucosal immunity H Willemse, PN Smith, PG AIDS Vaccine, Boston, MA, US Board, MG Casarotto and AF Dulhunty M Yabas Human aging and expression of proteins ATP11C mutation causes X-linked interacting with the ryanodine receptor in B cell deficiency with diminished skeletal muscle phosphatidylserine internalization Australian Orthopaedic Association ACT IFReC-SIgN Winter School on Advanced branch Annual Scientific Meeting, Sydney, Immunology, Awaji Island, Hyogo, Japan NSW Flipping of lipids by a putative transporter is essential for B-cell development and H Willemse, PN Smith, PG function Board, MG Casarotto and AF 3rd European Congress of Immunology, Dulhunty Glasgow, UK Human aging and expression of proteins interacting with the ryanodine receptor in Y Zhu skeletal muscle Quantifying the influence of sequence Joint AuPS/PSNZ/ASB Meeting, Sydney, neighborhood on mutation NSW Australian Society of Medical Research New Investigator Forum, Canberra, ACT

Annual Review 2012 119 Community

Ms Nur Diana Anuar Associate Professor John M Dr Anneke Blackburn Member: Australia-Malaysia Muslim Bekkers Coordinator: Cancer Biology Forum, Family Association (AMMF) Director: Australian Course in Advanced JCSMR, ANU, Canberra, ACT Member: Malaysian Postgraduate Neuroscience (ACAN), Moreton Bay Presenter and Host: JCSMR Outreach Student Association (MyPSA) Research Station, North Stradbroke Program, Canberra, ACT Island, QLD Organizing committee member: MyPSA Member: American Association for for GAZA Fundraiser, Canberra, ACT Reviewing Editor: Neuroscience Letters; Cancer Research Frontiers in Neuroscience; BMC Member: Australian Society for Medical Neuroscience Dr Stuart Archer Research (ASMR) Chair: JCSMR Scholarships Committee Grant-Assessor: NHMRC Member: Kathleen Cunningham Convenor: JCSMR School Seminar Consortium for Research into Familial Reviewer: PLoS One program Breast Cancer (kConFaB) Member: JCSMR Education Committee Invited Speaker: ACT Cancer Council Professor Mauricio Member: ANU Neuroscience Pink Ribbon Breakfast: Targeting cancer Arcos-Burgos Management Committee metabolism with dichloroacetate Editorial Board Member: Molecular Member: Eccles Institute of Neuroscience National Breast Cancer Foundation Genetics and Genomics Medicine Director Search Committee National Research Roadshow: Targeting cancer metabolism with dichloroacetate Editorial Reviewer: Nature Genetics; Council Member: Australasian Molecular Psychiatry; Human Genetics, Neuroscience Society Invited speaker: Zonta Club of Canberra Nephron; Bioinformatics; Translational Breakfast meeting: Targeting cancer Ex officio Member: ACAN Management Psychiatry, Annals of Human Genetics; metabolism with dichloroacetate Committee of the Australasian The ANU Undergraduate Research Neuroscience Society Journal Professor Philip G Board Member: Australasian Neuroscience Society Member: ACT Gene Technology Advisory Ms Bhavani Balakishnan Council Member: Australian Physiological Society Presenter and Host: Academic visit from Awards Committee Member: International Member: Society for Neuroscience US Indiana University Purdue University Society for the Study of Xenobiotics (IUPUI) Member: International Brain Research Editorial Board Member: The Open Drug Organization (IBRO) Workshop Presentation: Missense Metabolism Journal; Drug Metabolism Mutation Project, a gene driven approach Presenter and Participant: National Youth Reviews; The Sirraj Medical Journal for generating mouse models for cancer Science Forum, JCSMR, ANU, Canberra, research, Lorne Cancer Conference, ACT Dr Jean-Didier Breton Lorne, VIC Presenter and Host: JCSMR Outreach Program, Canberra, ACT Chair: Neuroscience Seminar series, JCSMR, ANU, Canberra, ACT Dr Nicole Beard Judge: Australasian Brain Bee Challenge Co-organiser: Annual Neuroscience Presenter and Participant: National Youth Final, Australasian Neuroscience Society, Kioloa Colloquium, ANU Coastal Campus, Science Forum, JCSMR, ANU, Canberra, Gold Coast, QLD Kioloa, NSW ACT Presenter and Participant: Australian Chair: Organising committee: Gage Dr Edward M Bertram Brain Bee Challenge, ACT Regional Conference on Muscle Excitation- Steering Committee Member: Finals, JCSMR, Canberra, ACT Contraction Coupling International Mouse Phenotyping Member: Australasian Neuroscience Secretary: Gage Conference Society Consortium Society Academic Editor: PLoS One Finance Sub-Committee Member: Member: Society for Neuroscience US International Mouse Phenotyping Council Member: Australian Physiological Consortium Member: Federation of European Society Neuroscience Society Participant: Australian Government- Member: Cardiac Society of Australia and European Union 2nd Workshop on Member: French Neuroscience Society New Zealand Research Infrastructure Member: Biophysical Society US Mr Bob Buckley Member: The Australasian Genomics Technologies Association (AMATA)

120 The John Curtin School of Medical Research Dr Corinne Carle Member: Australasian Neuroscience Dr Vincent Daria Society Member: Australasian Neuroscience Co-Chair: Neurophotonics Session, Society (ANS) Member: Society for Neuroscience US European Conferences on Biomedical Member: Association for Research in Optics, Munich, Germany Vision and Ophthalmology Mr Aaron Chuah Presenter and Participant: National Youth Committee Member: Australian Society Member: The Australasian Genomics Science Forum, JCSMR, ANU, Canberra, for Vision Research Technologies Association (AMATA) ACT Presenter and Participant: JCSMR Open Presenter: Australian Course in Advanced Day, The John Curtin School of Medical Dr Jennifer Clancy Neuroscience (ACAN), North Stradbroke Research, ANU, Canberra, ACT Island, QLD Member: Australian Society for Editorial Board: ISRN Optics Presenter and Participant: National Youth Biochemistry and Molecular Biology Science Forum, JCSMR, ANU, Canberra, Member: Australasian Neuroscience ACT Member: Australian Society for Medical Society Research Presenter and Participant: Clinical Member: Optical Society of America Member: RNA Network of Australasia Research Suites Open Day, The John Member: The International Society for Curtin School of Medical Research, ANU, Member: JSCMR Operations Committee Optics and Photonics Canberra, ACT Grant-Assessor: NHMRC, ARC Member: Australian Optical Society Reviewer: Circulation Research; PLoS Dr Marco G Casarotto One; microRNA; F1000Research Dr Debjani Das Presenter and Host: JCSMR Outreach Program, Canberra, ACT Associate Professor Member: Cognitive Neuroscience Society Council Member: Australian Society for Matthew Cook Member: International Behavioural and Biochemistry and Molecular Biology Neural Genetic Society Chairman: Royal Australasian College (ASBMB) Member: Society for Social Neuroscience of Physicians, Joint Specialist Advisory Member: Australian Society for Medical Committee, Immunology and Allergy Member: Australian Society for Psychiatric Research (ASMR) Research Member: Royal Australasian College of Member: Australian Biophysics Society Physicians Curriculum committee Reviewer: Addiction; Addiction Biology; (ABS) PLoS ONE; Journal of Attention Member: Royal Australasian College of Disorders; Psychological Medicine; Member: Biophysical Society US Physicians College education committee Developmental Psychobiology; Social Member: NHMRC Grant Review Panel: Examiner: Royal College of Pathologists Psychiatry and Psychiatric Epidemiology Biochemistry and Cell Biology of Australasia (Immunopathology) Member: NHMRC Grant review panel Dr Michael Dobbie Dr Geeta Chaudhri Editorial Board Member: Clinical and Exhibition Booth Host: Research Member: American Society Virology Translational Immunology Infrastructure, Annual Australian Science Member: Federation of CLinical Communicators National Conference, Immunological Societies Ms Tiffany Cripps Sydney, NSW Member: Australasian Society for Member: The Australasian Genomics Immunology Technologies Association (AMATA) Dr Guowen Duan Member: International Society for Honorary Fellowship: CSIRO Cytokine and Interferon Research Dr Stephen Daley Professor Angela F Dulhunty Dr Julian Choy ACT Branch Councillor: Australasian Society for Immunology Immediate Past President: Australian Presenter and Participant: JCSMR Open Editor: News and Commentary section: Society for Biophysics Day, The John Curtin School of Medical Immunology and Cell Biology Research, ANU, Canberra, ACT Organiser: Curtin Conference on Muscle, Convenor: Celebration of Professor Chris Canberra, ACT Presenter and Participant: National Youth Parish’s Honorary Life Membership of Member: Australian Physiological Society Science Forum, JCSMR, ANU, Canberra, the Australasian Society for Immunology, ACT JCSMR, Canberra, ACT Member of the National Committee for Presenter and Participant: Australian Biomedical Sciences Brain Bee Challenge, ACT Regional Member: ARC College Finals, JCSMR, Canberra, ACT Member: Biophysical Society US

Annual Review 2012 121 Editorial Board Member: Calcium Binding Co-convenor: ANU Photosynthesis Member: Australian Physiological Society Proteins; Ion Channels; The Biochemical Initiative Scientific Committee Member: Australian Neuroscience Society Journal Fellow: Royal Australian Chemical Institute Member: ANZ Microcirculation Society Grant Assessor: ARC AusReader, Member: Australian Society for Member: American Physiological Society NHMRC, European, USA and NZ Biochemistry and Molecular Biology Granting agencies (ASBMB) Member: Society for Neuroscience US Member: Australian Society for Biophysics Dr Anselm Enders Dr Lauren Howitt ACT Branch Councilor: Australasian Dr Rebecca Haddock Presenter and Participant: National Youth Society of Immunology Science Forum, JCSMR, ANU, Canberra, Panel Member: NHMRC Early Career ACT Member: CMBE Research Committee Fellowships Member: Cardiovascular SIG Committee, Member: RSB Honours Convening Committee Chair: JCSMR Scholarships committee Australasian Society of Clinical and Committee Experimental Pharmacologists and Member: Australasian Society for Committee Member: Level A/B Toxicologists Immunology representative, JCSMR Executive Member: Australian and New Zealand Member: European Society for Committee Microcirculation Society Immunodeficiencies ACT Representative: Australian and New Zealand Microcirculation Society Associate Professor Gavin Professor Christopher C Member: National Association of Huttley Goodnow Research Fellows Member: Australian Physiological Society Convenor: Techniques in Computational Member: Australian Academy of Science Genomics Seminar Series Special Elections Committee Member: Australian Society of Convenor: Bioinformatics drop-ins Medical Science Review Board Member: Pharmacologists and Toxicologists Juvenile Diabetes Research Foundation (Cardiovascular SIG Committee member) Organising committee chair: Workshop on Bioinformatics for High Throughput Member: Infection and Immunity Strategic Sequencing Advisory Committee, The Wellcome Trust, Ms Angela Higgins UK Academic Head: Genome Discovery Unit Member: The Australasian Genomics Editorial Board Member: Immunity; Technologies Association (AMATA) Chair: Genome Discovery Unit Operations The Journal of Experimental Medicine; Committee Mammalian Genome; Journal of Member: Genetics Society of Australasia Autoimmunity; BMC Biology Professor Caryl E Hill Member: Society for Molecular Biology Guest Reviewing Editor: Journal of Communicating Editor: International and Evolution Immunology Physiology (London) Reviewer: PLoS Genetics; PLoS ONE Council Member: EMBL Australia Committee Member: Cardiovascular Special Interest Group, Australian Grant Reviewer: ARC, NHMRC program Member: Australasian Society for Physiological and Pharmacological grants Immunology Society Media interviews: The medical Member: American Association for the Committee Member: NHMRC Early significance of snake venom, ABC Radio, Advancement of Science Career Researcher Awards Committee AFP, 3AW Member: American Association of Presenter and Participant: National Youth Editorial Board Member: Frontiers in Immunologists Science Forum, JCSMR, ANU, Canberra, Evolutionary and Population Genetics; ACT Biology Direct; PLoS ONE Professor Jill Gready Committee Member: JCSMR Operations Member: Society for Molecular Biology and Evolution Presenter and Participant: JCSMR Open Committee Day, The John Curtin School of Medical Management Committee Member: Member: Genetics Society of AustralAsia Research, ANU, Canberra, ACT Histology, Electron Microscopy and Editorial Board Member: Bioinformatics FACS, JCSMR and Biology Insights Member: JCSMR Workshop Users Member: ANU Supercomputing Time Committee Allocation Committee Management Committee Member: ANU Centre for Advanced Microscopy

122 The John Curtin School of Medical Research Ms Carly Hynes Participant: National Scientists and Member: National Selection Committee: Mathematicians in Schools Program, in Australian-American Fulbright Organiser: NSW miRNA Users Workshop, association with Canberra Girls Grammar Commission RNA network of Australasia and ASBMB School, Deakin, ACT Committee Member: ANU Genome Reviewer: PLoS ONE Discovery Advisory Committee Member: The RNA Society Professor Julio Licinio Member: NHMRC - Promoting & Member: The Australian Society for Review Panel Member: US National Maintaining Good Health Expert Working Medical Research (ASMR) Institute of Mental Health, National Group Member: Australian Society for Institutes of Health Interventions President: International Society of Biochemistry and Molecular Biology Committee for Adult Mood and Anxiety Translational Medicine Disorders (ITMA) (ASBMB) Member: National Science Colloquium Member: United States Department of Member: Australasian Microarray and Review Panel Member: National Institute Health and Human Services, Secretary Associated Technologies Association for Health Research Biomedical Research Advisory Committee on Genetics, Health (AMATA) Centres and Biomedical Research Units, and Society Member: Golden Key International Scientific Program Committee Chair: Honour Society Member: NHMRC Genetics Review Panel American Psychiatric Association Organising Committee Member: Sarah Member, Membership and Scientific Mr Cameron Jack Grace Sarcoma Foundation Program Committees: American College Member: The Australasian Genomics of Neuropsychopharmacology Member: Australasian Society for Technologies Association (AMATA) Psychiatry Research Course Co-Convener: The Bootes Course on Translational Medicine, JCSMR, Editorial Board Member: Translational Dr Ben Kaehler Canberra, ACT Medicine: Current Research Journal Member: Genetics Society of AustralAsia Member: Scientific Program Committee: American College of Psychiatrists Associate Professor Brett Associate Professor Guna Member: Communications Committee: Lidbury Association for Clinical Research Training Karupiah Public lecture: Replacing Animals in Founding President: International Society Medical Research - A World View and the Vice-President: Federation of of Pharmacogenomics (ISP) Australian Perspective Immunological Societies of Asia Oceania House, Forrest, ACT (FIMSA) Member: American Society of Human Genetics Vice-President - Federation of Clinical Dr Fiona Lithander Immunological Societies (FOCIS) Member: Association for Patient-oriented Investigation Member: American Association of Member: Year 1 and Year 2 Examination Immunologists Member: Collegium Internationale Neuro- Committees, ANU Medical School, ANU, Psychopharmacologicum (CINP) Canberra, ACT Member: American Society for Microbiology Member: Society for Neuroscience US Member: Phase 1 Committee, ANU Medical School Member: American Society Virology Member: The Endocrine Society Member: American Federation for Medical Council Member: ACT Branch, Nutrition Member: International Society for Society of Australia Cytokine and Interferon Research Research Member: Nutrition Society Australia Member: Australasian Society for Member: Society of Biological Psychiatry Immunology Fellow: The Royal Australian and New Member: Australia New Zealand Obesity Society Member: Australian Society for Medical Zealand College of Psychiatrists Research (ASMR) Co-Chair: ANU College of Medicine, Member: Nutrition Society, UK & Ireland Biology & Environment, Committee for Member: Association for the Study of Professor Trevor D Lamb Academic Health Science Centre and Obesity, UK Translational Research Registered Nutritionist; Association for Consulting Editor: Journal of Physiology Editor-in Chief: Molecular Psychiatry Nutrition, UK Dr Yalin Liao Editor-in Chief: The Pharmacogenomics Judge: ASMR New Investigator Forum, Journal Canberra, ACT Member: Nutrition Society of Australia Editor-in Chief: Translational Psychiatry Presenter and Participant: Clinical Member: Canberra Society of Chinese Editorial Board Member: Australian and Research Suites Open Day, The John Scholars New Zealand Journal of Psychiatry Curtin School of Medical Research, ANU, Canberra, ACT

Annual Review 2012 123 Dr Fabio Longordo Dr Claudio Mastronardi Professor Christopher R Presenter and Participant: JCSMR Open Member: Society for Neuroscience US Parish Day, The John Curtin School of Medical Member: The Endocrine Society Medical Research Advisory Committee Research, ANU, Canberra, ACT Member: The Australian Cancer Research Organising Committee Member: Clinical Foundation Member: Australasian Neuroscience Research Suites Open Day, The John Society Curtin School of Medical Research, ANU, Committee Member: Melbourne Member: Swiss Neuroscience Society Canberra, ACT International Congress of Immunology 2016 Bid Member: Society for Neuroscience US Professor Klaus I Matthaei Founding Member: World AllergoOncology Task Force (Vienna- Professor Ted Maddess Deputy Chair: ANU Institutional based) Director: ARC Centre of Excellence in Recombinant DNA Biosafety Committee Vision Science Reviewer: Royan Institute International Dr Ian Parish Section Editor: Clinical and Experimental Research Awards Member: Australasian Society for Ophthalmology Reviewer: National Health & Medical Immunology Session Chair: International Imaging and Research Council News and Commentary Editor: Perimetry Society meeting Reviewer: AUSReader Australian Immunology and Cell Biology Chair: Organising Committee: AOVSM Research Council meeting, Melbourne, VIC Affiliate Member: Centre for the Molecular Dr Hardip Patel Member: American Academy of Genetics of Development Neurology (AAN) Member: Australian Physiological Society Member: The Australasian Genomics Technologies Association (AMATA) Member: American Academy of Member: ANZ Microcirculation Society Ophthalmology (AAO) Member: Genetics Society of Australasia Member: Association for Vision Research Dr Peter Milburn and Ophthalmology (ARVO) Dr Gilberto Paz-Filho Member: The Association of Biomolecular Member: Imaging and Perimetry Society Resource Facilities (ABRF) (US) Editorial Board Member: Brazilian (IPS) Archives of Endocrinology and Metabolism Member: International Society for Clinical Dr Teresa Neeman Electrophysiology of Vision (ISCEV) Member: Latin American Thyroid Society Member: Safety monitoring committee: Member: Royal Australian & NZ College of Otsuka clinical trial in patients with COPD Member: Brazilian Society of Ophthalmology (RANZCO) Endocrinology and Metabolism Member: Safety monitoring committee Member: Optical Society of America for Immunotherapeutics clinical trial of Member: The Endocrine Society (OSA), Vision Sciences Society (VSS) monoclonal antibody in patients with Committee Member: The Endocrine Member: Board of Administration: multiple myeloma Society’s International Endocrine Scholars National Vision Research Institute Statistical reviewer: Cochrane Program Task Force (Melbourne) Collaborative Acute Respiratory Infections Committee Member: The Endocrine Member: Scientific Advisory Board of Group Society’s Trainee & Career Development EyeCo Pty Ltd Statistical reviewer: Cochrane Core Committee Organising Committee Member: Collaborative Breast Cancer Group Committee Member: The Endocrine International Imaging and Perimetry Statistical consultant: MS Australia Society’s Awards Review Committee Society, Melbourne, VIC External Assessor: National Health and Member: Eccles Institute of Neuroscience Dr Maxim Nekrasov Medical Research Council Project Grants Director Search Committee Workshop host and Presenter: Chromatin Organising Committee Member: The Member: Zinkernagel/Doherty Fellowship techniques in Plants, Monash University, 3rd Bootes Course on Translational Selection Committee, JCSMR Melbourne, VIC Medicine: The Pathway from Discovery Member: Board of Directors, Australian to Healthcare, The John Curtin School of College of Optometry Medical Research, The Australian National Ms Stephanie Palmer University, Canberra, ACT Member: Board of Administration, National Vision Research Institute (NVRI) Member: The Australasian Genomics Co-convenor: Masters of Translational Technologies Association (AMATA) Medicine program at The Australian Member: NHMRC Assigners Academy National University, Canberra, ACT

124 The John Curtin School of Medical Research Organising Committee Member and Host: Member: Professional Behavioural Technology Zurich, Centre de Regulació Clinical Research Suites Open Day, The Committee, ANU Medical School, The Genòmica Barcelona (Spain) John Curtin School of Medical Research, Australian National University, Canberra, Editorial Board Member: PLoS ONE ANU, Canberra, ACT ACT Reviewer: Cell; Science; Nat Cell Biol; Member: Honours Neuroscience PLoS Biol; EMBO J; TIBS; Genome Biol; Dr Kaiman Peng Committee, JCSMR, ANU NAR; RNA Member: The Australasian Genomics Representative: Brazilian Higher Technologies Association (AMATA) Education Delegation to Australia, ANU Mrs Anne Prins Medical School, ANU, Canberra, ACT Presenter and Participant: National Youth Ms Eva Pillai Professor Thomas Preiss Science Forum, JCSMR, ANU, Canberra, Equity Officer: ANU Postgraduate and ACT Research Student Association (PARSA) Member: Australian Society for Presenter and Host: JCSMR Outreach Biochemistry and Molecular Biology PARSA Representative: ANU College of Program, Canberra, ACT Medicine, Biology and the Environment Chair: RNA network Australasia, an Presenter & Co-organiser: Surgical Cut on the Postgraduate Representative ASBMB SIG Up Workshops, CIT, Bruce, ACT Council Member: Australasian Microarray & Presenter & Co-organiser: Surgical Cut Postgraduate Representative: ANU Associated Technologies Association Up Workshops, Launceston, TAS Education Committee, HDR Sub- Member: German Society for Demonstrator: Anatomical Pathology, CIT committee Biochemistry and Molecular Biology and University of Canberra, Bruce, ACT Member: ANU Access and Equity Board Member: Lorne Genome Inc Committee Member: Australian Genome Conference Professor Jan Provis Senior Residential Scholar: Toad Hall, Organising Committee 2012, Lorne, VIC Postgraduate Residence Member: Scientific Advisory of the Symposium co-chair, ComBio Conference Ophthalmic Research Institute of Australia 2012, Adelaide, SA (ORIA) Dr Jason Potas ANU Representative: University round Chair: Research Grants Advisory Group, Member: Australasian Neuroscience table of Research Australia Retina Australia Society Deputy Chair: Research Committee Associate Director: ARC Centre of Member: Brazilian Society of CMBE/ANU Excellence in Vision Science Neuroscience and Behaviour SBNeC Member: ANU Major Equipment Member: Scientific Review of Progress – Presenter and Participant: JCSMR Open Committee ClemCell Project, Bond University. Day, The John Curtin School of Medical Member: JCSMR External Relations Member: Bendigo Bank Scholarship Research, ANU, Canberra, ACT Committee Advisory Group, Braidwood-Bungendore Presenter and Participant: Australian Member: JCSMR Internal Grant Review District. These scholarships are for Brain Bee Challenge, ACT Regional Committee students entering tertiary education and Finals, JCSMR, Canberra, ACT are in need of and eligible for financial Member: JCSMR Group Leaders’ Forum Presenter and Participant: National Youth support. Science Forum, JCSMR, ANU, Canberra, Grant-Assessor: NHMRC, ARC, National ACT Heart Foundation, Clive and Vera Ramaciotti Foundation, Sylvia and Charles Mr Roy Ramiscal Member: Year 1 and year 2 Examination Viertel Foundation, Cure Cancer Australia Member: Australasian Society for Committees, ANU Medical School, The Foundation, Children’s, Youth and Immunology Australian National University, Canberra, Women’s Health Service, South Australia, Member: JCSMR Education Committee ACT Marsden Fund (NZ), Université de Liège Member: Phase 1 Curriculum Committee, Concerted Research Actions (Belgium), Member: JCSMR Social Committee ANU Medical School, The Australian Swiss National Science Foundation, National University, Canberra, ACT Austrian Science Fund (FWF), Cancer Dr Charani Ranasinghe Research UK, Wellcome Trust UK, NSF Member: Phase 1 Assessment (USA), Foundation for Polish Science, Member and Volunteer worker: Committee, ANU Medical School, The French National Research Agency (ANR), Belconnen Arts Centre Australian National University, Canberra, and European Research Council ACT Member and Volunteer worker: AIDS CAP committee/ (PhD) thesis examiner: Action Council ACT Member: Medical Science Theme UNSW, University of Sydney, University Committee, ANU Medical School, The Member: Australasian Society for of Newcastle, UQ, UWA, University Australian National University, Canberra, Immunology of Adelaide, Swiss Federal Institute of ACT

Annual Review 2012 125 Member: Society for Mucosal Mr Geoff Sjollema Associate Editor: Frontiers in Cellular Immunology Neuroscience Workshop Presentation: Missense ACT representative: ASI Mucosal Mutation Project, a gene driven approach Advisory Editorial Board: Trends in Immunology Special Interest Group for generating mouse models for cancer Neurosciences Editorial Board: Journal of Sexually research, Lorne Cancer Conference, Member of Council: Sydney Chapter of Transmitted Diseases Lorne, VIC the US Society of Neuroscience Organising Committee: Australian Society Member: Australasian Neuroscience for HIV Medicine (ASHM) Conference, Dr Tanya Soboleva Society Melbourne, VIC Participant: Scientists in Schools Member: Australian Academy of Science program, in association with Telopea Park Member: Society for Neuroscience US Dr Danny Rangasamy School Barton, ACT Member: Australian Neuroscience Society Grant Assessor: NHMRC Member: Society of Reproductive Biology Symposium Programming and Advisory Associate Editor: Biotechnology Letters Group (SPAG) Member: Australian Society for Dr Zan-Ming Song Biochemistry and Molecular Biology Editorial: Journal of Community Medicine Dr Norimitsu Suzuki (ASBMB) and Health Education Presenter and Participant: National Youth Editorial: Scientific World Journal Science Forum, JCSMR, ANU, Canberra, Ms Belinda Ryan ACT Member: ASBMB Associate Professor Member: Australasian Neuroscience Society Christian Stricker Member: Society for Neuroscience US Ms Tennille Sibbritt Chair: Medical Science Committee, ANU Medical School, ANU, Canberra, ACT Member: Australian Epigenetic Alliance Dr Rebecca Sweet Member: Australian Society for Chair: Year 2 Examination Committee, Biochemistry and Molecular Biology ANU Medical School, ANU, Canberra, Presenter and Participant: JCSMR Open (ASBMB) ACT Day, The John Curtin School of Medical Research, ANU, Canberra, ACT Member: Golden Key International Presenter and Participant: National Youth Honour Society Science Forum, JCSMR, ANU, Canberra, Member: Australasian Society for ACT Immunology Member: The RNA Society Presenter and Participant: Indigenous Day, ANU Medical School, ANU, Professor David Tremethick Dr Charmaine Simeonovic Canberra, ACT Committee member: ACT branch of the Editorial Board Member: Cell Reference Group Member: Independent Australian Society for Medical Research Management Group, National Baboon Transplantation ACT representative: The Australian Colony, Camperdown, NSW Member: The Australasian Society for Society of Biochemistry and Molecular Immunology Member: ANU Neuroscience Biology Management Committee Member: The Transplantation Society of Editorial Board Member: Chromosoma; Australia and New Zealand. Member: Australasian Neuroscience Epigenetics; Epigenetics & Chromatin; Society Member: The Transplantation Society Open Biology (International) Member: Society for Neuroscience US Member: Lorne Genome society Member: The International Pancreas and Member: Australian Society for Islet Transplant Association Professor Greg J Stuart Biochemistry & Molecular Biology Member: The Immunology of Diabetes Instructor and presenter: Australian Member: American Society for Society (International) Course in Advanced Neuroscience Microbiology Member: The International (ACAN), North Stradbroke Island, QLD Session Chair: ComBio Conference, Xenotransplantation Association Convenor: Australian Brain Bee Adelaide SA Member: The Cell Transplantation Society Challenge, ACT Regional Finals, JCSMR, Canberra, ACT Member: The Australian Diabetes Society Organiser: Kioloa Neuroscience Colloquium, ANU Coastal Campus, Kioloa, NSW

126 The John Curtin School of Medical Research Dr Krisztina Valter Professor Bruce Walmsley Dr Kerong Zhang Co-Chair: Block1 ANU Medical School, Editorial Board Member: Biology Image Member: The Australasian Genomics ANU, Canberra, ACT Library Technologies Association (AMATA) Member: Year 1 and Year 2 Examination Presenter: Hearing Awareness Week ACT Committees, ANU Medical School, ANU, Expo, Canberra, ACT Yicheng Zhu Canberra, ACT Member: Australasian Neuroscience Member: The Australian Society for Member: Phase 1 Committee, ANU Society Medical Research (ASMR) Medical School, ANU, Canberra, ACT Member: Society for Neuroscience US Member: Genetics Society of AustralAsia Member: Medical Science committee, (GSA) ANU Medical School, ANU, Canberra, Professor Ma-Li Wong ACT Member: Neuroscience Honours Associate Editor: Molecular Psychiatry Committee, JCSMR, ANU, Canberra, Editorial Board Member: The ACT Pharmacogenomics Journal; Clinical Member: Association for Research in Pharmacology, Advances and Vision and Ophthalmology (ARVO) Applications; Journal of Experimental Pharmacology. Member: European Vision and Eye Research (EVER) Reviewer: Melbourne Health, Royal Melbourne Hospital, Melbourne, VIC Member: International Society of Ocular Cell Biology (ISOCB) Fellow: The Royal Australian and New Zealand College of Psychiatrists Member: Australian Neuroscience Society (ANS) Member: PhD Scholarship Committee, JCSMR Member of Australia and New Zealand Association for Clinical Anatomists Member: Education Committee, JCSMR (ANZACA) Member: Postdoc selection committee, Member: CUBE NET JCSMR Department of Genome Biology, Computational Genomics Group Presenter and Participant: National Youth Science Forum, JCSMR, ANU, Canberra, Member: Animal Services Review ACT Committee Participant: Scientists and Member: Zinkernagel/Doherty Fellowship Mathematicians in Schools Selection Committee, JCSMR Member: Curriculum Planning Day, Mr Jorge Vélez Academic Unit of Psychiatry & Addiction Medicine, ANU Medical School Member: Grupo de Neurociencias, Member: American Association for University of Antioquia, Medellín, Advancement of Science Colombia Member: American College of Neuropsychopharmacology Professor Carola Vinuesa Member: American Psychiatric Member: MHMRC Women in Science Association Working Committee Member: International Society for Member: Australasian Society for Pharmacogenomics Immunology Member: The Endocrine Society Member: American Association of Member: Society for Neuroscience US Immunologists Member: The Australian Society for Member: JCSMR Executive Committee Psychiatric Research Member: Collegium Internationale Neuro- Psychopharmacologicum (CINP)

Annual Review 2012 127 128 The John Curtin School of Medical Research Support to The School

Grants Financial Overview Donors Corporate Sponsorship

Annual Review 2012 129 Grants

Agency for Science Australian Research Council Professor T Preiss and Dr T Technology and Research Centre of Excellence in Beilharz (A* Star) – Singapore Vision Science Role of mRNA polyadenylation control in gene expression Dr A Tan Professor T Maddess and Dr A $35,000 Post-Doctoral Support James Professor CG Vinuesa $20,839 Advanced multifocal analysis of blinding diseases The role of Roquin in microRNA function and decay $273,000 American Australian $170,000 Association Dr J Paris and Dr K Valter-Kocsi Structure and function of primate macula Dr R Sweet Australian Research Council $168,000 US to Australia Fellowship LIEF Grant $30,000 Australian Research Council Professor L Botten, Professor D Leinweber, Professor L Radom, Discovery Project Grants Australian Centre for HIV Professor J Gready et al. and Hepatitis Virology Professor S Easteal, Dr R Williams, Strengthening merit-based access and Research Grant Dr LS Jermiin and Dr DG MacArthur support at the new National Computing Infrastructure petascale su-percomputing The role of short tandem repeat DNA facility Dr C Ranasinghe and Dr R variation in the evolution of human Jackson psychological diversity $650,000 Design an effective poxvirus based $82,000 vaccine for HIV-1 by modulating immune Bayer Bioscience Research cell milieu using an IL-10 antagonist Associate Professor G Huttley and Co-operative Grant $136,000 Dr VB Yap Improving the accuracy of phylogenetic Professor J Gready ANU Discovery Translation reconstruction by improving models of Design of variant Ribulose-1 sequence divergence Fund 5-bisphosphate caboxylase/oxygenase $80,000 proteins with improved catalytic efficiency and substrate specificity Professor M-L Wong and Dr NA Beard, Professor AF $415,092 Professor J Licinio Dulhunty and Professor R Dirksen Evaluating a novel pharmacological How triadin and junctin communicate treatment for obesity and metabolic Beta Therapeutics Pty Ltd with ryanodine receptors deep within syndrome a calcium store to determine skeletal Discovery Translation Fund $81,836 muscle contraction Project Grant $100,000 ANU Major Equipment Professor C Parish and Dr C Dr VR Daria, Associate Professor Committee Simeonovic C Stricker, Professor S Redman, $114,669 Professor T Preiss Professor H Bachor and Professor Understanding transcriptome dynamics: G Stuart Bioplatforms Australia Ltd/ quantitating changes in cellular RNA Using light to probe brain activity in 3D Education Investment Fund $100,000 $143,000 Professor S Easteal Professor T Lamb, Professor I Professor D Tremethick $200,000 A high-capacity high-throughput Potter, Associate Professor N Hart, superspeed centrifuge Professor S Collin and Professor D Cancer Australia $49,000 Hunt The evolution of light detection and its Dr A Blackburn and Professor P impact on early vertebrate evolution Board $10,000 Targeting of two aspects of metabolic (TOTAM) for cancer therapy $20,000 130 The John Curtin School of Medical Research Commonwealth Department Garnett Passe and National Health & Medical of Regional Australia Local Rodney Williams Memorial Research Council Australia Government Arts and Sport Foundation Fellowship Anti-Doping Research Professor B Walmsley Professor CC Goodnow Program How does sound-induced quantal New strategies to reveal the genetic and Professor S Easteal, Dr J neurochemical release in the cochlea cellular basis of immunological disease generate impulses in the auditory nerve? Henderson, Dr R Williams, Ms S $800,000 Tan, Dr C Gore and Dr M Ashenden $96,246 Novel high throughput c-DNA sequencing National Health & Medical to identify a genomic signature for Grains Research and Research Council Career autologous blood transfusion Development Corporation Development Fellowships $17,016 Professor J Gready Dr N Beard Department of Industry, Identifying Wheat Germplasm with Control of cardiac and skeletal Superior Rubiscos for Breeding for Innovation, Climate contractility by luminal calcium store load Increased Drought Tolerance in health and disease Change Science Research $349,990 $96,040 and Tertiary Education (DIICCSRTE) Australia-India Human Frontier Science Dr A Enders Strategic Research Fund Program Investigating B cell development maintenance and high-affinity antibody Dr D Rangasamy, Professor P Dr R Sweet production by ENU mutagenesis Board and Dr N Lenka The role of T cell derived interferon $97,769 An insertational mutagenesis approach gamma in lupus associated anxiety and to identify epigenetic factors that control depression National Health & Medical embryonic stem cell differentiation $36,150 Research Council $90,000 Development Grant Juvenile Diabetes Research Department of Industry, Foundation – National Dr C Ranasinghe and Professor I Innovation, Climate Health and Medical Ramshaw Change Science Research A novel strategy to enhance T cell- Research Council Special mediated immunity to vaccine antigens and Tertiary Education Program Grant $76,834 (DIICCSRTE) National Professor C Parish, Dr C Collaborative Research Simeonovic, Dr C Freeman and Dr National Health & Medical Infrastructure Strategy G Hoyne Research Council Early Dr S Winslade, Professor C Role of heparan sulfate, heparanase and Career Fellowship heparanase inhibitors in the development Goodnow and Ms A McKenzie and prevention of Type I diabetes Dr D Ryan Australian Phenomics Network Super Investigations into the mechanism and Science Project $600,000 function of the chromatin remodelling $4,000,000 complex SWI-SNF Medical Advances Without Animals Trust $68,723

Associate Professor B Lidbury Sponsorship ANU Hosted Fellowship Program $151,885

Annual Review 2012 131 National Health & Medical National Health & Medical Professor AF Dulhunty, Dr NA Research Council Research Council Program Beard and Dr DR Laver Equipment Grant Grant Regulation of calcium release channels (RyR2) in healthy and failing hearts Dr A Cook Professor C MacKay, Professor J $108,525 Countess cell counter Sprent, Professor CC Goodnow, Dr Professor AF Dulhunty, Dr MG F MacKay, Professor CG Vinuesa, $7,199 Casarotto and Professor PG Professor A Basten, Professor B Board Professor A Dulhunty Fazekas de St Groth, Dr S Tangye Prep Cell Pump and Fraction Collector and Dr R Brink DHPR β subunit binding to a variably spliced region of RyR1: A role in EC $20,725 Molecular and cellular studies of the coupling and myotonic dystrophy adaptive immune response in health and Professor S Easteal disease $178,902 MultiNA MCE-202 microchip $1,086,841 Dr A Enders and Professor C electrophoresis system for DNA/RNA analysis Goodnow National Health & Medical Understanding the pathogenesis and $6,515 Research Council Project heterogeneity of autoimmunity as failure of multiple steps Professor C Goodnow Grants ELISA Plate Reader $162,209 Dr NA Beard, Professor AF $42,780 Associate Professor G Huttley and Dulhunty and Professor S Gyorke Dr W Meyer Dr D Ryan Unique isoform-specific regulation of Uncovering the genetic basis of fungal Infors MultiTron2 Temperature Controlled cardiac ryanodine receptors by calcium virulence Shaking Incubator store proteins $82,893 $25,130 $135,375

Professor D Tremethick Associate Professor JM Bekkers Associate Professor G Karupiah and Dr G Chaudhri New “HyD” high sensitivity detector for and Dr M Larkum Understanding the key attributes of CD8 Leica confocal microscope Neural circuits for odour-processing in the T cell receptor transfer as an antiviral $27,681 rodent piriform cortex in vitro strategy and harnessing the process to $173,902 combat persistent viral infections National Health & Medical Associate Professor JM Bekkers $197,244 Research Council and Professor S Nelson Associate Professor G Karupiah Postdoctoral Training Excitability and hyperexcitability of neural and Dr T Newsome circuits in the rodent piriform cortex Fellowships Actin-based motility as a virulence $113,250 mechanism and potential as an antiviral Dr R Haddock target Obesity and diabetes: Understanding Professor PG Board, Professor AF cardiovascular risk factors and Dulhunty, Dr MG Casarotto and $75,000 identification of novel targets for treatment Professor L Arnolda Professor T Maddess, Dr A $71,812 New cardiac ryanodine receptor inhibitors James, Dr C Carle, Professor C for the treatment of heart failure Dr I Parish Nolan and Dr R Essex $197,244 Regulation of CD8+ T cell dysfunction Novel functional testing for early diabetic retinopathy during tolerance and chronic viral infection Professor AF Dulhunty, Professor L $71,250 Arnolda, Dr A Blackburn and Dr N $232,761 Beard Professor C Parish and Dr B Quah Anthracyclines disrupt Ca2+ signalling in Analysis of antigen receptor sharing by T cardiomyocytes: a contribution to cardiac and B lymphocytes toxicity $173,902 $143,775

132 The John Curtin School of Medical Research Professor T Preiss and Dr J Professor DJ Tremethick National Institutes of Health Clancy Mechanisms underpinning the epigenetic (US) Project Grants Exploring the role of miRNA and code and the role of histone variants target processing variability in cardiac $181,130 Professor AF Dulhunty and hypertrophy Professor R Dirksen $194,895 Professor CG Vinuesa, Dr D Yu and Control of calcium movements in muscle Associate Professor A Liston Professor T Preiss and Dr J $19,278 (in conjunction with The Specialised subsets of T follicular helper University of Rochester, NY, US) Mackay cells in the control of infection and Designer RNA-binding proteins for immune pathology Professor C Goodnow, Associate research and therapeutic purposes $166,130 Professor G Karupiah, Dr R $25,000 Bertram and Professor R Ulevitch Professor I Young and Professor P Professor T Preiss and Dr N Control systems governing short vs long Foster term humoral and cellular immunity McMillan Targeting miRNA to inhibit leukocyte $802,954 (in conjunction with The RNA interference and the immune system differentiation: a novel anti-inflammatory Scripps Research Institute) approach for the treatment of asthma $36,750 $96,835 Professor C Goodnow, Professor R Dr C Ranasinghe Ulevitch and Professor B Beutler Professor I Young, Professor D Ollis Enhancement of mucosal immunity and Systems approach to immunity and CTL avidity against HIV-1 and Dr J Murphy inflammation Cytokine-driven allergic inflammation: $82,951 $630,442 (in conjunction with The characterization of two isoform-specific Scripps Research Institute) Dr K Randall modes of IL-3 receptor activation and Investigation of cellular abnormalities investigation of new receptor-associated Professor C Goodnow, Professor R signalling partners and synapse formation in Dock8 Ulevitch and Professor B Beutler immunodeficiency $199,895 Systems approach to immunity and $102,500 inflammation - Annotation National Health & Medical Professor GJ Stuart $128,418 (in conjunction with The Research Council Research Scripps Research Institute) Properties of dendritic spines and their role in synaptic plasticity Fellowships Clive and Vera Ramaciotti $108,250 Professor T Preiss Foundation Major Research Professor GJ Stuart $128,371 Award Cortical mechanisms underlying binocular Professor C Vinuesa vision Professor CC Goodnow and Dr A $128,371 $119,736 Enders Ramaciotti Immunization Genomics Professor GJ Stuart National Health & Medical Laboratory Regulation of cortical excitability by Research Council Senior $200,000 GABAB receptors Research Fellowship $109,736 Associate Professor G Karupiah Professor DJ Tremethick $128, 371 How chromatin compaction is regulated and its link with disease $158,902

Annual Review 2012 133 Financial Overview

Staff numbers 2012 2011 Academic staff * 77.66 77.3

General staff — administration, technical & support *º 139.73 112.3

HDR students (EFTSL) 80.5 80.8

Postgraduate coursework students (EFTSL) 1.0 1.0

* The figures are for Full Time Equivalents, as at 31 December, and exclude casuals º Includes Animal Service Facility staff

Recurrent and Special Purpose Funds $ Total Income 2012 2011 Student Fees 256,498 263,128 Other Income 22,539,733 21,099,088 Internal Sales 4,824,596 1,942,631 Internal Allocations 374,239 1,439,069 Operating Grant 17,754,231 14,830,000 Investment Income 167,841 246,906 Total Income 59,190,771 39,820,821

Total Expenditure Salaries & Related Costs 25,904,582 20,917,247 Equipment - Capital 1,585,596 1,499,671 Equipment - Non-Capital 633,287 353,247 Scholars Expenses 931,822 999,829 Utilities & Maintenance 2,080,295 1,504,424 Travel Field & Survey Expenses 900,232 901,881 Expendable Research Materials 10,434,045 9,379,950 Other Expenses 8,526,002 7,791,057 Total Expenditure 60,096,112 43,347,306

Transfers Inflow/(Outflow) Transfer from other 13,609,314 6,597,903 Transfers to other 9,100,251 4,003,920 Total Transfers Inflow/(Outflow) 4,509,063 2,593,983

Net Current Year Operating Result 905,342 -932,501 Prior Year Cash Result 19,674,634 13,020,263 Net Operating Position 18,769,292 12,087,762

134 The John Curtin School of Medical Research Donors

The Director, staff and students of Mrs Mary Appleby Ms Dorothy Mangos JCSMR are extremely grateful for the Mr Jock Bartram Mrs Thelma Maurice continued generosity and support of our friends and donors. Ms Meryl Bartram Mr John McConville Gifts and bequests to the School are used Ms Pam Bartram Ms Joan McDonald to fund vital medical research projects Mr Gary Borradale Ms Jennifer McEniery as well as providing scholarships and Mr Ron Brown Mrs Lyn McKnight purchasing specialised equipment. Your support can be provided in a number Mrs Joan Byrne Ms Jenni McMullan of ways including a gift or bequest that Ms J Cawthray Mr John Milne may assist in funding a particular area of research, or a scholarship or prize. Mr Norman Clough Mr Phil Muttukumaru If you would like to discuss options for Ms Jennifer Copley J Newton supporting JCSMR, please contact: Ms Lyn Dalton Mr John O’Dor Dr Madeleine Nicol Dr Maria Dano Mrs L O’Sullivan T 02 6125 2577 Mrs Daphne Douglas Ms Rosslyn Paul E [email protected] Mr Keith Dunstan Ms Glenis Pearson The Tom Efkarpidis Foundation Mr Philip Pickersgill Mrs Judith Ford Mr Neil Power Our thanks go to those who have so Mr Jock Gavel Research Australia generously supported The John Curtin Medical Research Foundation at ANU Mr Albert Green Mr Denis Regan during 2012. Mr Peter Griffith 3 RNSWR Association Details can be found on their website: Mrs Bev Harvey Mrs Rhonda Robinson jcmrf.anu.edu.au Mr Bradley Harvey Mr Gordon Rogers Ms Cynthia Harvey The Sarah-Grace Sarcoma Foundation Mr Kieren Harvey Mrs Gwendolyn Schulz Mr R Harvey Mr Felix Scudamore Mr Robin Harvey Ms Lea Sublett Mr Leslie Hawkes Ms Sue Sullivan Mr Ross Holmes Mr John Tuck The John James Memorial Foundation Mr Robert Tupper Staff of Joint Operations Command, Mr Thomas Tyrrell Department of Defence Ms Debbie Vipond Mrs Robyn Jones Mr Gary Vipond Mr David Kennemore Mr Brett Walker Mr Ellis Lalor Mr Steven Warren Mr Gordon Lauder Mr Jeff West Mr John Lee Mrs Susan West Ms Louise Lee Mr Robin Yule Miss Lydia Lobb Professor Teddy Maddess

Annual Review 2012 135 Corporate sponsors

John Morris John Morris Scientific Service plus Solutions Scientific

136 The John Curtin School of Medical Research The John Curtin School of Medical Research ANU College of Medicine, Biology and Environment Building 131, Garran Road Acton ACT 0200 Australia T +61 2 6125 2550 F +61 2 6125 2337 E [email protected] W jcsmr.anu.edu.au CRICOS #00120C MO_13251