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Research Themes |
Dr
J Bekkers
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Cerebral Cortex Laboratory We study the brains of rodents in order to understand how synapses operate and how synaptic signals are added together to generate the flow of information in the central nervous system. We work in two main areas: - (1) the primary olfactory cortex, with the aim of understanding how the brain recognises and remembers odours, and
- (2) hippocampal cultures, in order to study fundamental questions about synaptic transmission.
The techniques we use include patch clamping (in cultures, in brain slices, and 'in vivo'), fluorescence microscopy, molecular biology, and computer modelling. |
Professor
PG Board |
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Molecular Genetics Inherited factors can
modify susceptibility to a range on research interests include molecular
genetic studies of glutathione linked enzymes and their roles in drug metabolism
and cancer. The use of drug metabolising enzymes in gene therapy for cancer.
Glutathione transferase structure and function. |
| Dr
N Beard |
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Cardiac Muscle Research Our focus is on understanding how Ca2+ mishandling by the Ca2+ store in the heart leads to several clinical disorders which results in severe cardiac toxicity and sudden death. Our lab uses techniques such as single ion channel studies, Ca2+ binding and release measurements, as well as a variety of ways to study protein-protein interactions. We investigate the specific molecular mechanisms that link alterations in cardiac Ca2+ homeostasis to cardiac disorders catecholamine-induced polymorphic ventricular tachycardia (CPVT) and anthracycline-induced cardiotoxicity.
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Dr MG Casarotto |
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Biomolecular Structure The structural
elucidation of biomolecules such as peptides, proteins and drug compounds
form the basis of understanding the function of many biological systems.
Magnetic resonance spectroscopy used in conjunction with kinetic and molecular
biology techniques provides the means by which the structure-function relationship
of targeted biomolecules are explored. |
| Dr G Chaudhri
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Infection and Immunity - Immune Mediators Laboratory. We study the host immune response to viral infection and the disease processes that sometimes ensue as a result of an over-exuberant response. Viruses have evolved strategies that try and evade the host response so the outcome of an infection is a result of the race between virus and host. We are interested in learning more about evasion mechanism of viruses as a way of better understanding the immune system and also to explore how they may be applied to potential therapies. Using influenza virus and poxvirus models, we are studying the role of inflammatory cytokines, particularly Tumour Necrosis Factor (TNF), in virus-host interactions and in the outcome of infection. |
Professor
AF Dulhunty |
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Muscle Physiology Regulation of calcium during contraction in normal
and skeletal and cardiac muscle. We focus on the very important and
essential ryanodine receptor calcium release channel and its regulation
by the calcium binding protein, calsequestrin. We examine effects of
mutations in these proteins that lead to debilitating skeletal
myopathies and to sudden cardiac death. The topics are approached using
single ion channel studies in conjunction with other
electrophysiological biochemical and structural techniques.
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Professor
S Easteal |
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Predictive Medicine - The Evolution of Human Diversity and its Impact on Health and Disease. My interests are in how the evolutionary dynamic between humans and their environments has shaped the complexity of human biology, given rise to human diversity and left a lasting impact on our health and wellbeing. I have a particular interest in the role of natural selection in the evolution of differences in personality, cognitive style and social behaviour, its impact on heath, welfare and human potential, and its implications for education, healthcare and the management of organizations and social institutions. Current work in my lab involves analysis of variation at specific genes to identify and characterise both signals of natural selection and associations with personality and behavioural traits, measures of cognitive performance, and health outcomes. The evolutionary analysis is underpinned by a substantial collection of genetic samples from human and other primate species. We are developing and applying new approaches to detecting and measuring the effects of diversifying selection in non-equilibrium populations. Our work on phenotype associations is based on large, longitudinal population-based cohorts with extensive health, life history, psychometric and neuroimaging data. I also work on the contribution of genetic variation to high performance. I plan to extend our previous work on athletic performance to include cognitive and behavioural performance in academic, business and other demanding contexts.
The work is carried out in a collaborative environment that includes clinicians, epidemiologists, psychologists, bioinfomaticians and molecular geneticists. I am particularly interested in genes involved in dopamine and serotonin signaling in the brain and hormone receptors, such as the vasopressin, oxytocin and estrogen receptors, with important functions in the central nervous system. Possible projects include: The evolutionary dynamics of genes associated with variation in cognition, personality and behaviour; the role of dopamine receptor variation in clinically identified subtypes of attention deficit hyperactive disorder in adults; the role of genes on late age cognitive decline and brain atrophy; the role of oxytocin and vasopressin receptor variation on social behaviour and behavioural disorders; the role of genes encoding components of the dopamine and serotonin system in anxiety disorders, including post-traumatic stress disorder; genetic variation associated with athletic performance.
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Professor
C Goodnow |
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Immunogenomics The sequence
of the human and mouse genome provides an unparalleled opportunity to
understand how the immune system is regulated in health and disease, and
to identify new ways to prevent or correct the numerous health problems
that arise from inappropriate immune responses. We combine state-of-the-art
genomics, cellular, and molecular immunology technologies to elucidate
the mechanisms that translate our genome sequence into healthy regulation
of immune responses, focussing on
mechanisms of self-tolerance and autoimmune diseases such as diabetes
and systemic lupus, on mechanisms of immunological memory, and on the
regulation of lymphomas and leukemia.
Australian Phenomics Network This new Major
National Research Facility houses a range of large initiatives to decode
how the genome sequence of humans and other mammals specifies the "phenome":
ie the collective phenotypic characteristics and performance of our tissues
and organs. Because of close sequence and functional homology between
human and mouse genes, collections of laboratory mice with subtle changes
in the genome sequence serve as the key "Rosetta Stone"
for decoding genome-phenome links and identifying how to identify, prevent
or cure major human and animal health problems. |
Professor
JE Gready |
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Computational Proteomics and Therapy Design
Our major focus is the co-evolution of protein structure and function, and
the origins of the relevant genes. Major areas of current interest are:
definition of enzyme binding and reaction mechanisms; comparative evolution
of prion protein and its homologues (Doppel and Shadoo); divergent evolution
of function in C-type lectin domain containing (CTLD) receptors; and development
of new computational methods to study protein-ligand structure, energetics,
and dynamics, and protein evolution. Our particular strengths are in coupling
computer-based methods and experiment, such as in prediction of enzyme mechanisms
and transcription-factor binding sites for gene expression, protein re-design
and finding new genes, with followup experimental test. |
Professor
CE Hill |
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Blood Vessel Laboratory The autonomic
synapse group is involved in studies of the formation and function of synapses
between autonomic nerves and their target cells, especially those of the
cardiovascular system. Studies in small arterioles are concerned with the
intracellular mechanisms underlying the coordination of nerve-mediated,
agonist-induced and spontaneous contractions. |
| Dr
G Hoyne |
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T Cell Development and Regulation The research in the laboratory is focussed on the development of self-tolerance to organ-specific antigens using a model of type 1 diabetes. Additional projects include investigating mechanisms controlling T cell homeostasis and T cell leukaemia. |
| Dr G Huttley |
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Computational Genomics. Our research spans several traditional scientific disciplines that are now largely amalgamated under the label of Bioinformatics - comparative and population genomics, mathematical statistics and computer science. Students in my group need to have some facility with programming, either formally (in terms of course work) or an aptitude for it. Other valuable backgrounds are evolutionary biology, mathematical statistics and computer science. |
| A/Professor
G Karupiah |
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Infection and Immunity - Host Defence Laboratory Our research is directed towards a better understanding of virus-host interactions and the immune response to infection with a view to develop more effective vaccines and selective treatments that would minimize the damaging effects of an established infection. We are pursuing this goal using a range of viral (e.g. pox, influenza A and herpes) and animal models. Our studies allow us to dissect the roles of leukocyte subsets, cytokines, antibody and a number of signalling molecules in viral infection and disease. The immune effector mechanisms that are generated to control and clear virus instead often cause immunopathology that has serious, sometimes lethal, consequences for the host. We have therefore directed our research effort toward dissecting out the immunological parameters that allow the rapid resolution of virus infection with minimum pathology. These studies are being carried out in parallel with others that attempt to reveal the many strategies that viruses have evolved to subvert the host immune response. |
| Dr
M Kole |
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Neuronal Integration - Mechanisms of axonal signalling
Nerve cells of the brain are connected by axons. To encode information action potential signals are generated within the axon and via rate and temporal patterns transmitted throughout the axon. An understanding of the action potential properties within individual neurons is therefore a prerequisite to understand how neuronal networks transmit and store information. In our lab we use a novel approach of patch-clamp and/or imaging techniques in brain slices (in vitro) to study the elementary steps of action potential initiation and propagation within cortical myelinated axons of single and connected neurons of the cortex. Research projects are available to further identify the role of voltage-gated channels in axonal signalling or to study the properties of axon signalling during epilepsy.
Reference: Kole MHP, Letzkus JJ and Stuart GJ (2007). Axon initial segment Kv1 channels control axonal action potential waveform and synaptic efficacy. Neuron. 55 (4); 633-47 |
| Professor
T Lamb |
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Photoreceptor responses to light.
We record the electrical responses of rod and cone photoreceptors to illumination,
using two very different approaches: (1) 'Suction pipette' recordings
from single photoreceptors cells isolated from the retina, and (2) Electroretinogram
(ERG) recordings from the living human eye. In both cases we are interested
in 'transduction', the response of the cell to illumination, as well as
in 'adaptation', the mechanism whereby the cell is able to adjust its
properties so as to function over a wide range of intensities. Additional areas of study include the responses of retinal bipolar cells,
measured using ERG recording, and the dark adaptation recovery of human
subjects following exposure to intense illumination
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| Dr M Lobigs |
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Molecular Virology Research into the biology of flaviviruses
at the molecular, cellular and whole animal level in order to develop stategies
for the prevention of flaviviral disease. Our current investigations are
focused on (i) diverse aspects of replication, assembly, virulence and pathogenesis
of dengue and encephalitic flaviviruses using mutagenesis and 'reverse genetics'
approaches and (ii) the contribution of innate, humoral and cellular immune
responses to the recovery from and/or immunopathology in flavivirus infection. |
| Professor
KI Matthaei |
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Gene Targeting Using genetic engineering
to generate transgenic or gene targeted (knockout) mice with a specific
genetic makeup to create mouse models of human disease. Current collaborations
involve work on allergy and asthma, nerve regeneration, vascular disorders,
host-parasite relationships, drug de-toxification and cancer. |
| Dr Matthias
Regner |
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Viral Immunology We focus on the role of cytotoxic
T cells and Natural killer cells in infection with poxviruses and encephalitic
RNA viruses. The mechanisms used to recognize and destroy virus-infected
cells are of particular interest. Potential projects for postgraduate research
students would be in the areas of:
• Mechanisms of immune evasion by poxviruses.
• Vaccine research.
• Innate and cytotoxic T cell responses during viral infection. |
Professor
CR Parish |
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Cancer and Vascular Biology This group
has been working for a number of years on the molecular basis of cell adhesion,
cell migration and cell invasion. with a particular emphasis on the immune
system, tumour metastasis and the growth of new blood vessels (angiogenesis).
Of particular interest has been the role of anionic carbohydrates, such
as heparan sulfate, in these processes. Recent research has also concentrated
on the development of novel cancer vaccines. In addition the Group aims
to apply its basic research findings to the development of new drugs which
inhibit inflammation, cancer spread and angiogenesis. |
Professor
I Ramshaw |
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Viral Engineering and Cytokines Research
interests include the construction of recombinant genetic vectors for a
variety of infectious agents including HIV. The study of cytokine gene
co-expression to enhance immunity is another important aspect of our work. |
| Dr
D Rangasamy |
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Epigenetics and Genome Stability
Our laboratory studies epigenetic control of retrotransposons in the mouse and human genomes. Retrotransposons are biologically active mobile DNA elements that can destabilise the genome, shaping genomic landscapes by insertional mutagenesis, deletion and gene rearrangements. Given the deleterious nature of retrotransposon activity, normal cells must have control mechanisms for transposon activity including DNA methylation, packaging retrotransposons into inactive heterochromatin structures and silencing by repeat-associated small noncoding siRNA pathways. We are interested in mechanisms by which the L1 retrotransposon is regulated in normal healthy cells. Of particular importance is to understand the roles of L1 retrotransposons and their epigenetic control in chromosomal stability and gene regulation, both in normal and diseased cells. |
| Dr C Raymond |
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Learning and Memory We study a phenomenon known as 'synaptic
plasticity', in which the connections (synapses) between neurons can be
strengthened or weakened according to experience. Such plasticity is believed
to underlie information storage, or memory, in the brain. In particular,
we are interested in long-term potentiation (LTP) of synaptic transmission
in the hippocampus, a region of the brain that is heavily involved in memory
formation. We study LTP using a variety of techniques including electrophysiology
to record the electrical activity from neurons, and 2-photon laser scanning
microscopy to visualise changes in various chemical components within neurons.
Raymond CR (2007) LTP forms 1, 2, and 3: different mechanisms for the 'long' in long-term potentiation. TINS 30(4): 167-175. |
| Professor
MF Shannon |
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Gene Expression and Epigenomics When the cells of the immune system detect an infection or injury, they respond by undergoing dramatic changes in their gene expression profiles. These changes in gene expression are crucial for mounting a successful immune response and clearing the pathogen or dealing with the injury. There are many layers of control that operate in the cell nucleus to orchestrate the correct patterns of gene expression. Research in the laboratory focuses on the interplay between two of these layers; chromatin structure and inducible transcription factors. Of specific interest is the role of the NF-kB family of transcription factors in mediating changes in chromatin structure. These studies are directly relevant to cancer, autoimmunity and transplantation. |
| Dr
C Simeonovic |
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Diabetes and Transplantation The pathogenesis of autoimmune diabetes, interventions to prevent the progression of the disease process and the treatment of the established disease by pancreatic islet transplantation. Strategies are being developed to protect the integrity of pancreatic islet tissue from autoimmune damage and to facilitate the long-term survival of islet allografts without the use of conventional immunosuppression.
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Associate
Professor
C Stricker
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Neuronal Network We investigate the properties of synaptic transmission in the cerebral cortex, and the short and long-term changes in synapses
that underlie information transfer, learning and memory. In addition we are interested in calcium homeostasis, the role of calcium stores in synaptic transmission and information transfer, and the changes that occur during neurodegenerative
disorders such as Alzheimer's Disease. |
Professor
G Stuart |
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Neuronal Signalling Laboratory The brain is made up of billions of neurons connected to each other to form
specific neuronal networks. The main objective of my group is to understand
how individual neurons within these networks integrate the thousands of
synaptic inputs they receive. In addition, we are interested in how
activation of these networks changes during learning and memory formation,
and disease (epilepsy). We do this by recording from individual neurons in
vitro and in vivo using both electrophysiological (patch-clamp) and imaging
techniques (confocal and 2-photon).
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| Dr
ML Tierney |
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Molecular mechanisms of ion channel functionThe
ligand-gated ion channels combine the functionalities of a receptor and
an ion channel in a single protein, and mediate fast synaptic signalling
in the central nervous system. We endeavour to understand the function of
these multi-subunit protein complexes from the perspective of a protein
chemist, in both native and model systems. Recombinant expression systems
are used for both the functional analysis of intact receptors in host cells
and also structural studies of soluble domains. The study of native receptors
in neurons involves the use of electrophysiology, confocal microscopy, qRT-PCR
and siRNA gene expression knockdown. The study of model receptors includes
the use of electrophysiology, molecular biology, biochemistry, confocal
and electron microscopy and x-ray crystallography. The functional studies
are focused on GABAA receptors with an emphasis on drug modulation and receptor
clustering while structural studies include additional members of this protein
family. |
| Professor
D Tremethick |
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Chromatin and Transcriptional Regulation To
reconstruct in vitro, the in vivo process that remodel the structure of
chromatin to allow transcription factor binding and the subsequent formation
of a functional transcription complex. The experimental approach involves
combining in vitro, a chromatin assembly system with a transcription system.
The role of individual chromatin assembly components (including histone
variants, histone acetylation, HMG proteins, architectural transcription
factors) in the transcriptional activation process is also being investigated.
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| Dr CG Vinuesa
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Humoral Immunity and Autoimmunity
Humoral Immunity and Autoimmunity Group We study how microRNA mediated regulation of gene expression in T follicular (TFH) helper cells, prevents the development of autoimmune diseases including lupus, type 1 diabetes and autoimmune arthritis. We take advantage of our discovery of the Roquin tolerance pathway to dissect the contribution of TFH cells and germinal centres to the development of pathogenic autoantibodies and TFH-cell derived lymphomas.
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Professor
B Walmsley |
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Synapse and Hearing In order to understand
the highly complex functions of the brain, we must understand how individual
neurons communicate with each other. This communication occurs at specialized synaptic
contacts, and the overall aim of the Group
is to understand how synaptic strength is regulated, and how synaptic signals
are processed by target neurons. |
| Dr D Webb |
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Asthma and Allergy - Asthma and the Immune Response Asthma is a chronic inflammatory airways disease that arises from abnormal immune responses to environmental allergens. This persistent inflammation ultimately triggers structural changes to the airways to cause breathlessness and wheezing. The reason why some individuals get asthma is related to a genetic predisposition that allows an allergen-induced immune response to occur more easily. Asthma susceptibility is also compounded by irritants such as cigarette smoke, pollutants and viruses.
Our research is focused on two main themes:
How does exposure to environmental irritants enhance the ability of allergens to induce airway inflammation?
An enzyme, glutathione transferase Pi: GSTP1, which is found in bronchial epithelial cells, detoxifies irritating chemicals in pollutants and cigarette smoke. Analysis of diverse population groups suggests that a different form of this enzyme is more often found in asthmatics. Our studies using Gstp-null mice are the first to demonstrate that GSTP1 suppresses allergic airways disease and suggest factors that reduce the efficacy of this enzyme would allow the development of more severe allergic responses in the asthmatics.
How is allergic inflammation controlled?
Much of the airway damage in asthmatics is due to factors released by inflammatory cells. We have investigated molecules that control initiation of allergic inflammation and identified a novel molecule (Ym1/2), which regulates the function of immune cells and their secretion of factors associated with airway damage. Better understanding of the function of this molecule may generate new therapeutic approaches to controlling immune processes in asthmatics. |
| Dr
R Williams |
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Molecular Systems Biology Understanding genotype-phenotype correlations in mammalian systems, including humans, with an emphasis on developing new ways to examine inter-individual variation using genome-wide functional data.
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Professor
I Young |
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Cytokine Molecular Biology Molecular and
cellular biology of haemopoietic growth factors and their receptors; regulation
of cytokine gene expression; role and signalling mechanism of interleukin-5
in relation to asthma and eosinophils. Approaches include reporter gene
and DNA binding assays, site-directed mutagenesis, protein expression and
structure determination, gene targeting and transgenic animals. |
