projects at centenary institute · proliferation, differentiation and survival of cells and...

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Projects atCENTENARY INSTITUTE2018

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Welcome to Centenary! The Centenary Institute is an independent Medical Research Institute, affiliated with the University of Sydney and Royal Price Alfred Hospital.

Centenary’s work is at the cutting edge of Cancer, Inflammation and Cardiovascular research. With state-of-the-art facilities and researchers at the top of their field, Centenary offers a perfect balance of challenge and support that will enable you to expand your skills and knowledge as you consider your future in science. The Centenary Institute has a long history of helping students graduate with 1st Class Honours and an extensive PhD program for those who wish to further develop their research skills.

This booklet contains the list of projects that will be supervised at Centenary Institute in 2018.

If you have any questions of a general nature, please contact our Student Recruitment Officer, Sonya:

Email: [email protected]

Phone: 9565 6141

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Welcome to Centenary!

Table of ContentsHONOURS.................................................................................................................................- (TB Program) Dr Stefan Oehlers.............................................................................................- (TB Program) Prof Warwick Britton.........................................................................................- (Molecular Hepatology Laboratory) A/Prof Mark Gorrell.....................................................- (Liver Immunology Program) Dr Patrick Bertolino...............................................................- (Gene and Stem Cell Therapy Program) Dr Chuck Bailey...................................................- (Gene and Stem Cell Therapy Program) Dr Ulf Schmitz.......................................................- (Gene Regulation in Cancer Laboratory) Dr Justin Wong..................................................- (- (Vascular Biology Program) Prof Jennifer Gamble..............................................................- (Metabolite and Lipid Signalling Laboratory) A/Prof Anthony Don....................................- (Liver Injury and Cancer Program) Dr Devanshi Seth..........................................................- (Immune Imaging Program) A/Prof Guy Lyons....................................................................- (Diseases of the Aorta Laboratory) Dr Renjing Liu...............................................................- (ACRF Centenary Cancer Research Centre) Prof Phil Hogg....................................- (Melanoma Program) Dr Jessamy Tiffen......................................................................

MASTERS...................................................................................................................................- (TB Program) Dr Stefan Oehlers.............................................................................................- (TB Program) Prof Warwick Britton.........................................................................................- (Gene and Stem Cell Therapy Program) Dr Ulf Schmitz....................................................... - (Immune Imaging Program) A/Prof Guy Lyons....................................................................- (Diseases of the Aorta Laboratory) Dr Renjing Liu...............................................................- (Immune Imaging Program) Dr Kimberley Beaumont...................- (ACRF Centenary Cancer Research Centre) Prof Phil Hogg....................................

PhD............................................................................................................................................- (DNA Repair Lab) Dr Chris Jolly........................................................ - (TB Program) Dr Stefan Oehlers.............................................................................................- (Gene Regulation in Cancer Laboratory) Dr Justin Wong..................................................- (Metabolite and Lipid Signalling Laboratory) A/Prof Anthony Don....................................- (Immune Imaging Program) A/Prof Guy Lyons....................................................................- (Diseases of the Aorta Laboratory) Dr Renjing Liu...............................................................- (Vascular Biology Program) Prof Jennifer Gamble..............................................................- (ACRF Centenary Cancer Research Centre) Prof Phil Hogg....................................- (Melanoma Program) Dr Jessamy Tiffen......................................................................

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Honourswww.centenary.org.au/students/honours

Take your first step into a career in medical research with Centenary. Housing state-of-the-art imaging, cytometry and animal facilities, you will hone new skills and learn the latest techniques from internationally renowned researchers whilst building the foundations for a future that could see you make breakthroughs that save lives.

“Fascinating novel research? Check! State of the art facilities? Check! Brilliant and supportive staff? Check! Opportunities to present and publish? Check! Great Location? Check! Centenary? Check!”Ellie PowterFormer Honours Student and Research Assistant, Vascular Biology

Note: ‡ denotes Honours projects being run through the Department of Infectious Disease and Immunology

◊ denotes Honours projects being run through the Department of Pathology

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DR STEFAN OEHLERS TB ProgramEmail: [email protected]: 02 9565 6192

VASCULAR DYSFUNCTION IN MYCOBACTERIAL PATHOGENSIS ‡

Tuberculosis is now the deadliest bacterial disease affecting the world. Our research group uses the zebrafish model system to better understand and treat this disease. The zebrafish is an excellent model for the study of infectious diseases by live imaging. Mycobacterial infection drives the formation of complex aggregates of immune cells known as granulomas, and these can be readily visualised in zebrafish. Granulomas behave similarly to tumours in many ways including the way they recruit leaky blood vessels to the site of infection. We have shown that angiogenesis (Oehlers, Nature 2015, http://dx.doi.org/10.1038/nature13967) and vascular permeability (Oehlers, J Infect Dis 2017, http://dx.doi.org/10.1093/infdis/jiw355) fuel mycobacterial growth in zebrafish infection models. This project expand these findings by determining the effects of vascularisation on host immunity and mycobacterial physiology using a combination of in vitro cell culture assays, zebrafish infection experiments and mouse models of pulmonary TB.

IMAGING IMMUNE INTERACTIONS IN GRANULOMA-FORMING INFECTIONS ‡

Mycobacterial and cryptococcal infections are the two most important infections affecting HIV positive patients. Our research group uses the zebrafish model system to better understand and treat these infections. The zebrafish is an emerging model for the study of infectious diseases that complements existing the mouse research model in the Tuberculosis Research Program at the Centenary Institute.

Infection with mycobacteria or cryptococci results in the formation of complex aggregates of immune cells known as granulomas, and these can be readily visualised in zebrafish embryos by live imaging. This project will specifically study the immune cell interactions that occur during infection by Mycobacterium abscessus and Cryptococcus neoformans, two deadly but neglected opportunistic pathogens.

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The granulomatous response is a process by which the immune system contains pathogens and inanimate irritants by aggregating macrophages and lymphocytes about them. While it is beneficial to the host to contain chronic intracellular pathogens, such as M. tuberculosis and M. leprae, granulomas are implicated in immuno-pathological conditions, such as Crohn’s disease and vasculitis. Interestingly, patients undergoing immunotherapy for cancers can develop sarcoidosis, a condition characterized by granuloma formation in multiple tissues. The cross-talk between macrophages and T cells is essential for determining the outcome of the granulomatous responses, and distinct subsets of macrophages, pro- and -anti-inflammatory, and T cells can influence the outcome of such responses. In this project, you will be analysing different human tissues using cutting-edge technologies, such as multiplex immunofluorescence and imaging mass cytometry, to characterise the immune populations based on the location in distinct forms of granulomas and determine their impact on clinical outcomes. This project help us understand how distinct forms of granulomas form in response to infection or immunotherapy.

THE GRANULOMATOUS RESPONSE IN HUMANS: THE INTERPLAY BETWEEN INATE AND ADOPTIVE IMMUNITY ‡

Influenza viruses infect epithelial cells throughout the respiratory tract. The virus is responsible for about 3,000 deaths annually in Australia, costs our health system over $85 million dollars every year and leads to about 1.5 million lost days of work. Although vaccines are available and partially protective, there is a great need for drugs to reduce disease progression and virus transmission. We have discovered a chemical event that appears to control influenza infection of host cells. Our recent findings indicate that a chemical bond, known as a disulphide bond, in the influenza coat protein, haemagglutinin, is cleaved by a host factor during infection by the virus. This discovery could form the basis of a new treatment for influenza. Two classes of current anti-viral drugs are available, but both are plagued by the development of resistance. Targeting a host factor required for infection should be less prone to drug resistance.This project is a collaboration between the ACRF Cancer Research Centre and Tuberculosis Research Program in the Centenary Institute. The student will study the role of disulphide bond cleavage in influenza infection of respiratory cells in vitro and during in vivo infection of mice. The project involves biochemical assays, cell culture and viral assays, immunohistochemistry and analysis of host cytokine and cellular responses.

NOVEL INHIBITION OF INFLUENZA VIRUS INFECTION ‡

PROF WARWICK BRITTONTB ProgramEmail: [email protected]: 02 9515 5210

VACCINE INDUCTION OF TISSUE RESIDENT MEMORY CELLS TO PROTECT AGAINST TUBERCULOUS ‡

Tuberculosis remains an enormous health problem worldwide, and research into new tools to prevent infection is recognised by WHO as critical for controlling this major human pathogen. Mycobacterium tuberculosisis spread through the lungs and we have shown that vaccines that stimulate immunity within the lungs can protect against infection. Memory T cells are important for the long-term efficacy of vaccines, and recently a class of tissue resident memory T cells have been identified at mucosal surfaces. This project will examine whether novel TB vaccines developed by our group induce tissue resident memory cells in the lungs of immunised mice. These vaccines include recombinant influenza A viruses, recombinant BCG and protein vaccines that stimulate CD4 T cell responses to immuno-dominant proteins of M. tuberculosis. The transcriptional responses of the vaccine induced-tissue resident T cells will be examined. This project will provide opportunities to learn cellular and molecular immunological techniques including flow cytometry, tissue culture, cytokine assays and RT-PCR.

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A/PROF MARK GORRELLMolecular Hepatology LaboratoryEmail: [email protected] Phone: 02 9565 6152

STRUCTURE OF MERS VIRUS RECEPTOR ‡

CD26 is the cell surface receptor that MERS (middle east respiratory syndrome) virus uses to infect humans, camels and bats. MERS and SARS are related coronaviruses but use different receptors. MERS virus tends to cause illness in people with diabetes. The structures of soluble CD26 (DPP4; ADA binding protein) bound to the MERS spike protein and bound to the ADA protein have been solved. However, the cell surface form of CD26 has unforeseen features. Therefore, knowing the structure of the CD26 dimer/tetramer complete with its transmembrane domain is likely to provide an important new understanding of its interactions with MERS virus. This project will solve the structure of the transmembrane CD26 protein using the new state-of-the-art automated equipment. Inhibitors of the enzyme activity of CD26 can be used to produce co-crystals for exploring whether the cell surface and soluble forms of CD26 differ in their interactions with inhibitors. The new knowledge of the true structure and enzymatic activity of intact transmembrane CD26 will be important in understanding the roles of CD26 in MERS infection, leukocyte biology, fibrosis and diabetes.

REGULATING EXTRACELLULAR MATRIX DEGRADATION ◊

Extracellular matrix (ECM) dysregulation is the core process of tissue scarring and is driven by myofibroblasts. FAP is a unique protease that causes ECM degradation. The host lab was first to publish that FAP is made by liver fibroblasts and that the enzyme activity of FAP in human blood is elevated in patients with significant liver scarring (fibrosis/cirrhosis), and that it decreases following removal of liver fibrosis by liver transplantation. Therefore, activated liver fibroblasts are the major source of increased circulating FAP (cFAP). How FAP is shed from the surface of fibroblasts is not understood. It is important to understand this process to [1]Be better able to use a mouse to model human liver fibrosis; [2]To better understand liver fibrosis; [3]To better understand changes in cFAP. Sheddase is the term used for an enzyme that cuts off the ectodomain of a cell surface protein. Our hypothesis is a known sheddase is responsible for cutting cFAP off the cell surface. This project will use knowledge and skills in biochemistry and cell biology to identify the FAP sheddase. The outcome will be important in developing FAP-based diagnostics and therapeutics for liver fibrosis.

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DR CHUCK BAILEYGene and Stem Cell Therapy ProgramEmail: [email protected]: 02 9565 6171

FUNCTIONAL CONSEQUENCES OF MUTATION IN THE TUMOUR SUPPRESSOR CTCF IN CANCER ◊

Whole genome sequencing of cancer patient cohorts has revealed ~120 signifi-cantly mutated genes (SMGs) which play a key role in cancer development. The ‘master weaver of the genome’ protein CTCF, is a SMG primarily in endometrial cancer, as well as colorectal, stomach, breast and haemopoietic cancers. Our group was the first to demonstrate that the ubiquitous zinc finger (ZF) protein CTCF acts as a tumour suppressor gene. Here, we will characterise the genetic and functional consequences of somatic mutations in CTCF in promoting carci-nogenesis. Our data has showed that mutations in the 11-ZF region can result in a loss-of-function or even gain-of-function in CTCF, which has implications for can-cer development. We will analyse how acquired genetic lesions in CTCF alter the proliferation, differentiation and survival of cells and contribute to cellular transfor-mation in the following aims:1. Determining the consequences of CTCF ZF mutations using in vitro functional assays.2. Mapping the alteration in DNA binding of CTCF mutants using DamID.3. Functional analysis of CTCF ‘CRISPR knock-in’ mutations in our cancer cell mod-els.

DR PATRICK BERTOLINOLiver Immunology ProgramEmail: [email protected]: 02 9565 6186

Our group is recognised internationally for its contributions to Liver Immunology. Using a variety of transgenic mouse models, we were the first to demonstrate that high affinity naïve CD8 and CD4 T cells can be directly activated in the liver independently of lymphoid tissues, an activation that promotes tolerance. This property might explain why liver transplants are spontaneously accepted in several animal models and why pathogens infecting the liver, such as Hepatitis B and C viruses evade immune responses, leading to chronic infection and inflammation.

To understand how CD4 and CD8 T cells recognising an antigen in the liver “talk” to each other and whether low affinity CD8 T cells are more dependent on CD4 help than high affinity CD8 T cells, we have generated several recombinant adeno-associated viral vectors (rAAV) targeting specifically different proportions of hepatocytes to express wild type and mutant forms of the model antigen ovalbumin (OVA) with or without a CD4 epitope. The aim of this project is to use these vectors to determine how cognate CD4 help and CD8 T cell affinity influence the development of CD8 T cells towards tolerance or memory.

ROLE OF CD4 HELP IN SHAPING THE RESPONSE OF CD8 T CELLS RECOGNISING A LIVER-EXPRESSED ANTIGEN ‡

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Our team has been studying one of the hottest areas in gene regulation - alternative splicing. In 2013, we reported in the prestigious journal, Cell, that a form of alternative splicing called intron retention (IR) is an evolutionarily conserved mechanism to reduce gene expression. In recent work involving blood cells from diverse species we have shown IR as a widespread mechanism throughout cell biology. The ‘master weaver of the genome’ protein CTCF, which we have shown to act as a tumour suppressor in cancer, is a protein also implicated in alternative splicing. CTCF binds tens of thousands of sites genome wide and coordinates chromatin architecture often in a locus- and tissue-specific manner. Binding of CTCF is governed by DNA methylation, which has been shown to regulate alternative splicing.

We now seek to determine the unexplored role of CTCF in IR by1. shRNA knockdown of CTCF in MPRO monocytes to examine effects on IR.2. RNAseq of Ctcf heterozygous mice compared to WT mice.3. Whole genome bisulfite sequencing of DNA isolated from WT and Ctcf+/- mice.4. CTCF ChIPseq in tissues from WT and Ctcf+/- mice to examine CTCF binding genome wide.

THE ROLE OF CHROMATIN ORGANISING PROTEIN CTCF IN INTRON RETENTION ◊

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in senior Australians. CLL is a slow developing cancer affecting B cells. Genetic mutations acquired in these B cells result in their transformation into cancerous cells that can live longer and grow faster than normal B cells. Similar to many blood cancers, genetic alterations in CLL can be heterogeneous, and include point mutations, chromosomal deletions, amplifications and rearrangements. Recently the gene encoding the transcription factor Max Gene Associated (MGA) was shown to be recurrently deleted or mutated in CLL. Our hypothesis is that genetic inactivation of MGA promotes chronic lymphocytic leukaemia disease progression. We will test this hypothesis by analysing how acquired genetic lesions in MGA alter the proliferation, differentiation and survival of CLL cells: by1. Determining the consequences of MGA mutations using in vitro functional assays.2. Mapping the alteration in DNA binding of MGA mutants using DamID.3. Meta-analysis of MGA and MYC/MAX family members in cancer.4. Structure/function correlations of mutations in MGA.5. Characterisation of haemopoietic development in Mga het mice

THE ROLE OF MGA MUTATION IN CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) ◊

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DR ULF SCHMITZGene and Stem Cell Therapy ProgramEmail: [email protected]: 02 9565 6162

EPIGENETIC FINGERPRINTS AND THEIR IMPACT ON INTRON RETENTION ◊

In a newly established collaboration with the German Epigenome Programme (DEEP) we study epigentic causes for alternative splicing. We have exclusive access to next generation sequencing data, including RNA-seq, DNAsel-seq, Bisulfite-seq, ChIP-seq, and NOMe-seq data. These data were derived from various healthy and diseased tissues and cell types (e.g., adipocytes, hepatocytes, macrophages/monocytes, fibroblasts, epithelial cells and T-memory/effector cells).In this project our goal is to conduct a comprehensive analysis of epigenetic markers, and other cis- and trans regulatory factors, that may trigger or prevent alternative splicing events. A bioinformatics analysis aims to infer cause and effect relationships between DNA methylation, histone modifications, chromatin accessibility, nucleosome occupancy, small RNA expression, splicing factor expression and changes in alternative splicing. We will use this knowledge to explore and infer possible causes for aberrant splicing in disease using a machine-learning approach. We are looking for students with an interest in bioinformatics or computational biology who want to learn and apply methods of sequencing data analysis.

IDENTIFICATION AND CHARACTERIZATION OF FEVER-INDUCED MICRORNA EXPRESSION ◊

We discovered that the expression of RNA-binding motif protein 3 (RBM3), known to respond to cold stress and to modulate microRNA expression, was reduced in 30 febrile patients, and at fever-like temperature (40°C) in THP-1-derived macrophages. RBM3 expression is reduced during fever whether or not infection is demonstrable. Reduced RBM3 expression causes an increased expression of RBM3-targeted microRNAs.We believe that these microRNAs, which we termed thermomiRs, play a role in the response to fever and that they target endogenous pyrogens in order to realize a negative feedback mechanism, which may be crucial to prevent pathological hyperthermia.In this project, our goal is to identify all putative thermomiRs including novel yet uncharacterized microRNAs, whose expression increases or decreases under fever-like conditions. We generated small RNA sequencing data from THP-1-derived macrophages at both normal (37°C) and fever-like temperatures (40°C). The aim is to analyze this data for differentially expressed and novel microRNAs and to computationally predict effectors and putative downstream targets of thermomiRs.

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DR JUSTIN WONGGene Regulation in Cancer LaboratoryEmail: [email protected]: 02 9565 6175

HOW DOES ABNORMAL GENE PROCESSING LEAD TO BREAST CANCER? ◊

Our team has been studying one of the hottest areas in gene regulation - alternative splicing. In 2013, we reported in the prestigious journal, Cell, that a form of alternative splicing called intron retention (IR) is an evolutionarily conserved mechanism to reduce gene expression. Intron retention is an important mechanism that controls gene expression. In an analysis of 16 different cancer types, we identified increased intron retention in 15 types of cancers consistent with the role of intron retention in switching genes off. The only exception is breast cancer in which intron retention is reduced in cancers compared to adjacent normal controls. We hypothesise that derepression of intron retaining genes is a mechanism that switches on tumour promoting genes in breast cancer.

In this project we will use a state-of-the art RNA sequencing approach to identify tumour-promoting genes that are regulated by intron retention in breast cancer. Ultimately, we will proceed with studies in animal models and primary human breast cancer samples to confirm the importance of this unanticipated phenomenon in breast cancer development and potential impact on therapy.

DR RENJING LIUVascular BiologyEmail: [email protected]: 02 9565 6227

UNDERSTANDING CELLULAR TRANSDIFFERENTIATION FOR REGENERATIVE MEDICINE ◊Skeletal muscle stem cells have the ability to differentiate into various lineages including the osteogenic, adipogenic, and chondrogenic lineages. This ability to transdifferentiate makes muscle stem cells particularly attractive for regenerative medicine to treat a myriad of musculoskeletal disorders. However, the mechanisms that control the ability of these cells to transdifferentiate into particular lineages are largely unknown.

Epigenetics is the study of mechanisms that turn genes on and off. The Liu lab focuses on the role of epigenetic modifications (particularly DNA methylation) in the musculoskeletal and cardiovascular systems. This Honours project will determine the biological significance and function of a newly discovered family of DNA demethylases in regulating muscle stem cell transdifferentiation.

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DR DEVANSHI SETH Alcohol Liver DiseaseEmail: [email protected]: 02 9565 6268

IDENTIFICATION OF MIRNA AS RISK FACTORS FOR ALCOHOL INDUCED CIRRHOSIS IN CHRONIC DRINKERS ◊Risky drinking is a significant problem in Australia. Of more than 60 alcohol use disorders, Alcoholic Liver Disease (ALD) is the most common disorder of prolonged drinking associated with underlying addiction issues. Risk factors associated with the development of ALD in some drinkers remain largely unknown. Recent literature suggests that serum miRNAs may be important players in alcohol use disorders, impacting gut permeability, Kupffer cell activation, oxidative stress, inflammation in ALD and predicting structural/functional changes in the brain. However, comprehensive information on miRNAs that are specifically associated with chronic alcohol use, or those that influence the progression of liver injury in drinkers and their mechanism of actions are yet unknown.HYPOTHESIS: miRNAs are important epigenetic regulators in the development of ALD. Defining miRNAs as risk factors for alcohol induced liver injury will help in better understanding of the disease. We have available hundreds of serum specimens with extensive clinical and genetic data from chronic drinkers through another multinational study. It will identify novel potential diagnostic and therapeutic agents for ALD.

We know a lot about what induces disease. Atherosclerosis is the highest killer in theworld. Its development is linked to life-style risk factors, such as smoking, high fat diets,diabetes, hypertension and sedentary behaviour. Likewise for cancer, there are geneticfactors that predispose us to cancer together with life-style factors such as smoking,sun and asbestos exposure.We asked the question…”what protects us from developing disease,”We have identified a gene (ARHGAP18) whose expression is essential for the protection againstatherosclerosis and aneurysm development. Lack of this gene in mice results inenhanced atherosclerosis and thoracic aortic aneurysms upon exposure to chronicrisk factors. These results suggest that the vessels have active PROTECTIVE mechanismsagainst disease development. We also predict that the signaling pathways linked tothis gene may be used therapeutically to activate our natural defense mechanisms.Separate projects are available for Honours to:a. determine the MOLECULAR MECHANISM mediating this protection.b. determine the ROLE of the gene in human healthc. determine whether we can MANIPULATE the pathways to alter disease.

HOW DO WE PROTECT OURSELVES AGAINST DISEASE? (CANCER, CARDIOVASCULAR DISEASE, INFLAMMATION)

PROF JENNIFER GAMBLEVascular Biology ProgramEmail: [email protected]: 02 9565 6225

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NEW DRUGS TO PREVENT OBESITY AND DIABETES ◊

BACKGROUNDSpecific forms of the lipid “ceramide”, which are synthesized by different ceramide synthase enzymes, regulate insulin signalling and fat metabolism in key metabolic tissues. In this project, you will screen chemical libraries for new inhibitors of the enzymes ceramide synthase 5 and 6. These enzymes are very important regulators of sugar and fat metabolism in the liver and adipose tissues.

We will collaborate with chemists in the modification and improvement of these inhibitors, to yield new drugs that are likely to have a significant impact on diabetes and obesity.

TECHNIQUESSophisticated Metabolomic Mass Spectrometry to trace lipid metabolismCompound Library ScreeningMammalian Cell CultureMouse Models of High Fat Feeding and ObesityBiochemistry and Western Blotting

A/PROF ANTHONY DONLipid Metabolism and NeurochemistryEmail: [email protected]: 02 8627 5578

NEW DRUGS THAT ENHANCE FAT METABOLISM ◊

BACKGROUNDCurrent research indicates that triglyceride (fat) storage may be subject to control by the signalling lipid ceramide. More specifically, our current research shows that the enzyme ceramide synthase 1 regulates whole body adiposity. We have very recently developed and patented a specific inhibitor of ceramide synthase 1 that enhances triglyceride metabolism (fat “burning”) in skeletal muscle. This project has clear and important implications for the treatment of obesity and metabolic diseases.

AIMS1. Test new ceramide synthase inhibitors in cell culture and mouse models of high fat feeding.2. Determine the molecular basis for control of triglyceride levels by ceramides: does loss of Ceramide Synthase 1 activity enhance ß-oxidation of fatty acids in the mitochondria?

TECHNIQUESSophisticated Metabolomic Mass Spectrometry to trace lipid metabolismMammalian Cell CultureMouse Models of High Fat Feeding and ObesityBiochemistry and Western Blotting

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Defects in the cornea account for 4 million cases of blindness worldwide. The outermost layer of cells, the corneal epithelium, has a protective role and is the part of the eye that is most exposed to the UV radiation in sunlight. UV exposure is associated with corneal blindness, contributing to conditions in which the corneal epithelium is excessively thick (ocular cancers and pterygia), thin (keratoconus) or eroded (herpes virus activation). This project will use microscopic imaging of living corneal cells to determine how the thickness of the corneal epithelium is regulated and how UV radiation affects it. The activities of particular signalling pathways will be monitored within the cells using fluorescent reporter molecules. Our novel experimental models will identify better ways of preventing and treating conditions that contribute to corneal blindness.

A/PROF GUY LYONSImmune ImagingEmail: [email protected]: 02 9565 6127

HOW DOES SUNLIGHT CAUSE CORNEAL DISEASES? ‡

GENES AND CELL-CELL INTERACTIONS IN TUMOUR PROGRESSION ◊

Cancer is a disease in which cells acquire mutations in key genes that change their behaviour. Under pressures of limiting space and nutrients, cells that have an advantage in survival and proliferation are selected and dominate the tissue. This mutation and selection process is, in fact, an example of evolution. The clonal cooperation hypothesis of tumour progression predicts that genetically distinct clones of cells will evolve that interact in order for the tumour as a whole to progess to malignancy. These interactions allow the tumour cells to invade and metastasise.

We are interested in cancers that affect the tissues most exposed to the environment: the skin, the cornea and the oral cavity. This project investigates the role of cooperative interactions between clones of cells in driving tumour progression in these tissues. It uses live cell microscopy of genetically modified cells to identify what types of genes can interact in different individual cells. Computer simulations are used to predict the effects of these cell-cell interactions on the population of cells as a whole, and how they affect the clonal evolution of the cells.

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PROF PHIL HOGGACRF Centenary Cancer Research CentreEmail: [email protected]: 0423093870

NO CONTROL OF THROMBUS INITIATION ◊

Vascular thrombosis or clot formation is the underlying cause of heart attack, stroke and deep vein thrombosis. Recent studies from my lab and others have identified protein disulphide isomerase (PDI) as an essential component of clot formation and have validated it as a drug target. Our understanding of how PDI controls clot formation, however, remains immature. We have identified an interplay between PDI and nitric oxide (NO) in clot formation. NO is essential for maintaining circulating platelets and the blood vessel wall in a quiescent state. Our recent findings support a scenario in which PDI regulates clot formation by stripping NO from key clotting proteins during the rapid reduction in NO that occurs following vascular injury. NO adds a block or ‘encrypts’ the clotting proteins and PDI removes the block or ‘decrypts’ them. Our overall aim is to characterise this biological control and use the information to develop new anti-clotting drugs.

REDFINING THE ROLE OF VON WILLEBRAND FACTOR IN THROMBOSIS ◊

Vascular thrombosis or clot formation is the underlying cause of heart attack, stroke and deep vein thrombosis. von Willebrand factor (VWF) is a multimeric plasma protein that captures platelets to the injured blood vessel wall during thrombosis. Impaired control of VWF function is associated with life-threatening bleeding or clotting. von Willebrand disease is due to a qualitative or quantitative deficiency of VWF and is the most common hereditary coagulation abnormality described in humans. We have discovered that platelet capture by VWF is controlled by a redox switch in VWF. Our overall aim is to characterise this biological control and use the information to develop new anti-clotting drugs.

ESSENTIAL ROLE OF OXIDOREDUCTASES IN THROMBOSIS ◊

Mycobacterial infection drives the formation of complex aggregates of immune cells known as granulomas, and these can be readily visualised in zebrafish. Granulomas behave similarly to tumours in many ways including the way they recruit leaky blood vessels to the site of infection. We have shown that angiogenesis (Oehlers, Nature 2015, http://dx.doi.org/10.1038/nature13967) and vascular permeability (Oehlers, J Infect Dis 2017, http://dx.doi.org/10.1093/infdis/jiw355) fuel mycobacterial growth in zebrafish infection models. This project expand these findings by determining the effects of vascularisation on host immunity and mycobacterial physiology using a combination of in vitro cell culture assays, zebrafish infection experiments and mouse models of pulmonary TB.

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DR JESSAMY TIFFENMelanoma ProgramEmail: [email protected]: 02 9565 6226

TARGETING METHYLATION IN MELANOMA ◊

It is now recognised that epigenetic changes are an important driver of melanoma cancer growth and there is an increasing number of drugs that inhibit specific epigenetic targets. The Melanoma Research group is studying how some of these drugs may be beneficial in the treatment of melanoma.Such epigenetic modifications include methylation that causes abnormal silencing of tumour suppressor genes. Methyl groups can either be added to histone tails; around which DNA is wrapped to form chromatin, or directly to DNA itself. We have found that disrupting histone methylation leads to powerful cell death but only in a small percentage of melanoma cells. Our hypothesis is that combining this histone methylation inhibitor with a DNA methylation inhibitor may work even more effectively in a broader range of cells. The effects on cell growth and cell death will be measured using a number of techniques. Students will become adept at flow cytometry, western blotting, real-time RT-PCR, cell culture and gene knockdown by transfection of siRNA.

THE ROLE OF DEMETHYLASES IN MELANOMA ◊Abnormally high levels of methylation are a hallmark of cancer. KDM6A/B are important enzymes that remove methyl groups to maintain the right balance of methylation in cells and are frequently mutated/ inactivated in cancer. The aim of this project is to see whether this applies to melanoma.Databases produced by next-generation sequencing studies will be used to estimate the frequency of KDM6A/B mutations in melanoma and a panel of our cell lines will be screened for mutants. The effect of an inactivating mutation will be recapitulated in melanoma cells by knockdown of KDM6A/B. The effects on cell growth and cell death will be measured using a number of techniques. Students will become adept at cell culture, flow cytometry, western blotting and real-time RT-PCR.The aim of these projects is to produce results that can be published by the student, while providing training in essential scientific skills. Students will be supervised and instructed by post-doctoral scientists with considerable laboratory and scientific experience and excellent publication records.

TARGETING EZH2 IN MELANOMA ◊Australia has the highest incidence of melanoma in the world. More than 12,500 new cases of melanoma are diagnosed in Australia every year and 1500 die from metastatic melanoma. There is still no long term cure for metastatic melanoma as not all patients respond to current treatments and the development of drug resistance is a major problem.Our lab has identified the epigentic modifier EZH2 is abnormally activated in about one quarter of Australian melanoma patients and pre-clinical inhibitors of EZH2 show great promise. We seek to test these inhibitors in vitro and in vivo melanoma models to understand how they work and identify suitable candidate patients.We also seek to understand EZH2 biology and how abnormal EZH2 contributes to melanoma progression, particularly by repression of the anti-tumour immune response. This will be aided by our large collection of patient material from the Melanoma Institute Australia’s bio-specimen bank and cell lines.You will learn the relevant skills necessary for a successful career in science with hands on supervision and daily guidance from our experienced post-docs. You will publish your work in high impact factor journals.

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Masterswww.centenary.org.au/students/masters

Progress your research career by taking the next step with a Masters degree through the Centenary Institute. With state-of-the-art equipment, and an internal support system consisting of world-renowned scientists, the Centenary Institute can be the foundation for your promising career.

Our Masters program is designed as a perfect gateway to your PhD and enables you to further your skills on cutting edge flow and imaging machines, while working side by side with researchers at the top of their field.

Whatever you desire for your future in science, Centenary can empower you to achieve your goal and help you to get where you want to be.

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IMAGING IMMUNE INTERACTIIONS IN GRANULOMA-FORMING INFECTIONS‡


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PROF WARWICK BRITTONTB ProgramEmail: [email protected]: 02 9515 5210

THE GRANULOMATOUS RESPONSE IN HUMANS: THE INTERPLAY BETWEEN INATE AND ADOPTIVE IMMUNITY ‡The granulomatous response is a process by which the immune system contains pathogens and inanimate irritants by aggregating macrophages and lymphocytes about them. While it is beneficial to the host to contain chronic intracellular pathogens, such as M. tuberculosis and M. leprae, granulomas are implicated in immuno-pathological conditions, such as Crohn’s disease and vasculitis. Interestingly, patients undergoing immunotherapy for cancers can develop sarcoidosis, a condition characterized by granuloma formation in multiple tissues. The cross-talk between macrophages and T cells is essential for determining the outcome of the granulomatous responses, and distinct subsets of macrophages, pro- and -anti-inflammatory, and T cells can influence the outcome of such responses. In this project, you will be analysing different human tissues using cutting-edge technologies, such as multiplex immunofluorescence and imaging mass cytometry, to characterise the immune populations based on the location in distinct forms of granulomas and determine their impact on clinical outcomes. This project help us understand how distinct forms of granulomas form in response to infection or immunotherapy.

DR ULF SCHMITZGene and Stem Cell Therapy ProgramEmail: [email protected]: 02 9565 6162

EPIGENETIC FINGERPRINTS AND THEIR IMPACT ON INTRON RETENTION ◊

In a newly established collaboration with the German Epigenome Programme (DEEP) we study epigentic causes for alternative splicing. We have exclusive access to next generation sequencing data, including RNA-seq, DNAsel-seq, Bisulfite-seq, ChIP-seq, and NOMe-seq data. These data were derived from various healthy and diseased tissues and cell types (e.g., adipocytes, hepatocytes, macrophages/monocytes, fibroblasts, epithelial cells and T-memory/effector cells).In this project our goal is to conduct a comprehensive analysis of epigenetic markers, and other cis- and trans regulatory factors, that may trigger or prevent alternative splicing events. A bioinformatics analysis aims to infer cause and effect relationships between DNA methylation, histone modifications, chromatin accessibility, nucleosome occupancy, small RNA expression, splicing factor expression and changes in alternative splicing. We will use this knowledge to explore and infer possible causes for aberrant splicing in disease using a machine-learning approach. We are looking for students with an interest in bioinformatics or computational biology who want to learn and apply methods of sequencing data analysis.

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IDENTIFICATION AND CHARACTERIZATION OF FEVER-INDUCED MICRORNA EXPRESSION ◊We discovered that the expression of RNA-binding motif protein 3 (RBM3), known to respond to cold stress and to modulate microRNA expression, was reduced in 30 febrile patients, and at fever-like temperature (40°C) in THP-1-derived macrophages. RBM3 expression is reduced during fever whether or not infection is demonstrable. Reduced RBM3 expression causes an increased expression of RBM3-targeted microRNAs.We believe that these microRNAs, which we termed thermomiRs, play a role in the response to fever and that they target endogenous pyrogens in order to realize a negative feedback mechanism, which may be crucial to prevent pathological hyperthermia.In this project, our goal is to identify all putative thermomiRs including novel yet uncharacterized microRNAs, whose expression increases or decreases under fever-like conditions. We generated small RNA sequencing data from THP-1-derived macrophages at both normal (37°C) and fever-like temperatures (40°C). The aim is to analyze this data for differentially expressed and novel microRNAs and to computationally predict effectors and putative downstream targets of thermomiRs.







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A GENETIC AND EPIGENETIC APPROACH TO UNDERSTANDING ANEURYSM ◊Aneurysm is a pathological condition characterised by weakening of the vessel wall that eventually leads to rupture and death. It is a major cause of mortality worldwide, affecting 1 in 500 to 1000 individuals. Despite this, it is currently a significantly understudied disease where the causes of aneurysm formation are unknown.

The Aims of this PhD/Masters project are to:1. Identify novel gene, miRNA and protein changes during aneurysm development;2. Discover non-genomic changes involved in aneurysm pathogenesis, and provide the first comprehensive map of how DNA methylation patterns may be linked aneurysm development;3. Develop new drug targets that may modify and/or halt aneurysm progression.

Candidates will gain understanding and skills in molecular and cell biology techniques, animal models, histology, in vivo imaging, as well as transcriptome, proteome and epigenome screening.

EPIGENETIC REGULATION OF MIRNA IN CARDIOVASCULAR DISEASES ◊

Smooth muscle cells (SMC) are remarkably plastic and can switch between a differentiated and dedifferentiated phenotype, allowing for growth and repair. Imbalance between these SMC states is implicated in the pathogenesis of many major human cardiovascular diseases including atherosclerosis. MicroRNAs (miRNAs) are small noncoding RNAs that regulate genes via degradation or translational inhibition of their target mRNAs. miRNAs have been implicated to be significant regulators of SMC during vascular injury. The factors that regulate these miRNAs are however unclear.

Our previous work had identified the DNA demethylase TET2 as an epigenetic master regulator of the SMC phenotype. We have now identified two major classes of TET2-regulated miRNAs in SMC: those with a reported role in regulating stem cell pluripotency, and those previously described to regulate SMC plasticity.

The Aims of this project are to: 1) evaluate the roles of TET2-regulated miRNAs in SMC plasticity; 2) identify the mechanisms by which TET2-regulated miRNAs regulate SMC plasticity; and 3) determine the therapeutic utility of targeting TET2-regulated miRNAs in murine models of cardiovascular injury.

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UNDERSTANDING CELLULAR STEMNESS AND THEIR ROLE IN CARDIOVASCULAR DISEASES ◊

Cardiovascular disease is a leading cause of mortality worldwide. Inappropriate changes in vascular smooth muscle cell phenotype is a key underlying cause of many cardiovascular diseases including atherosclerosis, hypertension and aneurysms. Despite intense study, the mechanisms that regulate vascular smooth muscle phenotype remain largely unknown. We have now uncovered a novel stem cell pluripotency gene network that may in part be responsible for the plasticity of vascular smooth muscle cells, leading to the development of cardiovascular diseases.

The Aims of this Project are to:1. Demonstrate the biological and functional significance of this network in regulating smooth muscle plasticity;2. Identify the mechanisms that control this gene network in smooth muscle;3. Determine the therapeutic benefits of targeting this network in murine models of cardiovascular disease.Outcomes from this study may contribute to the development of novel therapeutic approaches to treat a plethora of major human cardiovascular diseases associated with aberrant smooth muscle plasticity, adding to the current therapeutic armamentarium.




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PhDwww.centenary.org.au/students/phd

Embrace the independence to pursue your desire of discovery. With state-of-the-art facilities, and an internationally renowned reputation, the Centenary Institute offers you the support and means to realise your dreams through pioneering breakthroughs and advancing the fight to find a cure.

The Centenary Institute has supported PhD candidates that have gone one to revolutionise medical practice and saving countless lives.

“I had many opportunities to present at a number of scientific meetings locally and abroad, and was successful in gaining awards and prizes for my presentations as well as competitive travel grants to attend these meetings.”Dr Philip TongFormer PhD Student, Immune Imaging

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DR CHRISTOPHER JOLLYDNA Repair LaboratoryEmail: [email protected]: 02 9565 6188

THE MECHANISM OF ANTIBODY HYPERMUTATION AND ITS ROLE IN B CELL CANCERS ‡

The activation of B cells during immune responses induces antibody affinity maturation and the switching of antibody isotypes. These processes lead to the production of high affinity antibodies able to penetrate tissues from which IgM (the starting isotype) is excluded, and depend on Activation-Induced Deaminase (AID), which damages Ig target DNA, recruiting mutagenic DNA repair. Antibody gene mutation is essential for optimal humoral immunity, but comes at a cost: AID-induced damage in “off-target” genes induces the Ig-translocations that typify most adult B cell cancers. We seek to understand why AID-induced DNA damage is repaired with low fidelity, when spontaneous forms of the same damage in other tissues are generally repaired with high fidelity. Using a unique “degron”-fusion approach in vivo, we have shown that the cell cycle timing of AID-induced DNA repair determines whether repair is mutagenic or faithful (Sharbeen et al. 2012 Journal of Experimental Medicine 209:965-74). This project will extend our findings to map when in the cell cycle DNA repair events induced by AID occur, and how AID-induced repair can be manipulated to prevent oncogenic translocations.

THE ROLE OF DNA REPAIR IN STEM CELL MAINTENANCE AND HYPERSENSITIVITY TO CHEMOTHERAPY OR RADIOTHERAPY ‡

Effective DNA repair is essential for the maintenance of stem cells. Mice and humans with specific DNA repair deficiencies (e.g. Fancomi’s anaemia or Lig4 syndrome) suffer from bone marrow failure and a pre-disposition to cancer as they age. Unfortunately, they also suffer devastating side effects if they undergo chemotherapy or radiotherapy to treat cancer. We have identified a new putative Fancomi anaemia gene in mice and developed a unique mouse model using CRISPR-mediated inactivation of this gene. This project will characterise the impact of this CRISPR mutation on stem cell function, DNA repair and the nuclear proteome using cutting-edge imaging, molecular bar-coding and cell biology tools. It will also screen specimens bio-banked from FA patients world-wide to screen for mutations in the new gene in humans

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IMAGING IMMUNE INTERACTIONS IN GRANULOMA-FORMING INFECTIONS ‡

Mycobacterial and cryptococcal infections are the two most important infections affecting HIV positive patients. Our research group uses the zebrafish model system to better understand and treat these infections. The zebrafish is an emerging model for the study of infectious diseases that complements existing the mouse research model in the Tuberculosis Research Program at the Centenary Institute.

Infection with mycobacteria or cryptococci results in the formation of complex aggregates of immune cells known as granulomas, and these can be readily visualised in zebrafish embryos by live imaging. This project will specifically study the immune cell interactions that occur during infection by Mycobacterium abscessus and Cryptococcus neoformans, two deadly but neglected opportunistic pathogens.

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DR JUSTIN WONGGene Regulation in Cancer LaboratoryEmail: [email protected]: 02 9565 6175

THE ROLE OF RNA PROCESSING DURING MONOCYTE DIFFERENTIATION ◊

Background: Our team focuses on alternative splicing; one of the most important mechanisms controlling gene expression and protein diversity. Our report in the eminent journal, Cell, described a form of alternative splicing called intron retention (IR) that is evolutionarily conserved to reduce gene expression in blood cells1. In recent work we have shown IR as a widespread mechanism in diverse cell types.

The Project: This project will expand our findings to determine the role of IR in the development of monocytes. Monocytes are pivotal to the innate immune system and play major roles in response to inflammation and infection. Nevertheless, our current understanding of detailed molecular mechanisms governing myeloid differentiation leaves open many opportunities for discovery. This project will utilise fluorescence activated cell sorting to isolate monocytes and their progenitors. It will also involve cell culture, RNA sequencing and high throughput qPCR to determine changes in gene expression and consequences of IR during monocyte differentiation.

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A/PROF ANTHONY DONLipid Metabolism and NeurochemistryEmail: [email protected]: 02 8627 5578

NEW DRUGS THAT ENHANCE FAT METABOLISM ◊

BACKGROUNDCurrent research indicates that triglyceride (fat) storage may be subject to control by the signalling lipid ceramide. More specifically, our current research shows that the enzyme ceramide synthase 1 regulates whole body adiposity. We have very recently developed and patented a specific inhibitor of ceramide synthase 1 that enhances triglyceride metabolism (fat “burning”) in skeletal muscle. This project has clear and important implications for the treatment of obesity and metabolic diseases.

AIMS1. Test new ceramide synthase inhibitors in cell culture and mouse models of high fat feeding.2. Determine the molecular basis for control of triglyceride levels by ceramides: does loss of Ceramide Synthase 1 activity enhance β-oxidation of fatty acids in the mitochondria?

TECHNIQUESSophisticated Metabolomic Mass Spectrometry to trace lipid metabolismMammalian Cell CultureMouse Models of High Fat Feeding and ObesityBiochemistry and Western Blotting

NEW DRUGS TO PREVENT OBESITY AND DIABETES ◊

BACKGROUNDSpecific forms of the lipid “ceramide”, which are synthesized by different ceramide synthase enzymes, regulate insulin signalling and fat metabolism in key metabolic tissues. In this project, you will screen chemical libraries for new inhibitors of the enzymes ceramide synthase 5 and 6. These enzymes are very important regulators of sugar and fat metabolism in the liver and adipose tissues.

We will collaborate with chemists in the modification and improvement of these inhibitors, to yield new drugs that are likely to have a significant impact on diabetes and obesity.

TECHNIQUESSophisticated Metabolomic Mass Spectrometry to trace lipid metabolismCompound Library Screening`Mammalian Cell CultureMouse Models of High Fat Feeding and ObesityBiochemistry and Western Blotting

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A GENETIC AND EPIGENETIC APPROACH TO UNDERSTANDING ANEURYSM ◊

Aneurysm is a pathological condition characterised by weakening of the vessel wall that eventually leads to rupture and death. It is a major cause of mortality worldwide, affecting 1 in 500 to 1000 individuals. Despite this, it is currently a significantly understudied disease where the causes of aneurysm formation are unknown.

The Aims of this PhD/Masters project are to:

1. Identify novel gene, miRNA and protein changes during aneurysm development;2. Discover non-genomic changes involved in aneurysm pathogenesis, and provide the first comprehensive map of how DNA methylation patterns may be linked aneurysm development;3. Develop new drug targets that may modify and/or halt aneurysm progression.

Candidates will gain understanding and skills in molecular and cell biology techniques, animal models, histology, in vivo imaging, as well as transcriptome, proteome and epigenome screening.

UNDERSTANDING CELLULAR STEMNESS AND THEIR ROLE IN CARDIOVASCULAR DISEASE ◊

Cardiovascular disease is a leading cause of mortality worldwide. Inappropriate changes in vascular smooth muscle cell phenotype is a key underlying cause of many cardiovascular diseases including atherosclerosis, hypertension and aneurysms. Despite intense study, the mechanisms that regulate vascular smooth muscle phenotype remain largely unknown. We have now uncovered a novel stem cell pluripotency gene network that may in part be responsible for the plasticity of vascular smooth muscle cells, leading to the development of cardiovascular diseases.

The Aims of this Project are to:1. Demonstrate the biological and functional significance of this network in regulating smooth muscle plasticity;2. Identify the mechanisms that control this gene network in smooth muscle;3. Determine the therapeutic benefits of targeting this network in murine models of cardiovascular disease.Outcomes from this study may contribute to the development of novel therapeutic approaches to treat a plethora of major human cardiovascular diseases associated with aberrant smooth muscle plasticity, adding to the current therapeutic armamentarium

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EPIGENETIC REGULATION OF MIRNAS IN CARDIOVASCULAR DISEASES ◊

Smooth muscle cells (SMC) are remarkably plastic and can switch between a differentiated and dedifferentiated phenotype, allowing for growth and repair. Imbalance between these SMC states is implicated in the pathogenesis of many major human cardiovascular diseases including atherosclerosis. MicroRNAs (miRNAs) are small noncoding RNAs that regulate genes via degradation or translational inhibition of their target mRNAs. miRNAs have been implicated to be significant regulators of SMC during vascular injury. The factors that regulate these miRNAs are however unclear.

Our previous work had identified the DNA demethylase TET2 as an epigenetic master regulator of the SMC phenotype. We have now identified two major classes of TET2-regulated miRNAs in SMC: those with a reported role in regulating stem cell pluripotency, and those previously described to regulate SMC plasticity.

The Aims of this project are to: 1) evaluate the roles of TET2-regulated miRNAs in SMC plasticity; 2) identify the mechanisms by which TET2-regulated miRNAs regulate SMC plasticity; and 3) determine the therapeutic utility of targeting TET2-regulated miRNAs in murine models of cardiovascular injury.

PROF JENNIFER GAMBLEVascular Biology ProgramEmail: [email protected]: 02 9565 6225

HOW DO WE PROTECT OURSELVES AGAINST DISEASE? (CANCER, CARDIOVASCULAR DISEASE, INFLAMMATION)

We know a lot about what induces disease. Atherosclerosis is the highest killer in theworld. Its development is linked to life-style risk factors, such as smoking, high fat diets,diabetes, hypertension and sedentary behaviour. Likewise for cancer, there are geneticfactors that predispose us to cancer together with life-style factors such as smoking,sun and asbestos exposure.We asked the question…”what protects us from developing disease,”We have identified a gene (ARHGAP18) whose expression is essential for the protection againstatherosclerosis and aneurysm development. Lack of this gene in mice results inenhanced atherosclerosis and thoracic aortic aneurysms upon exposure to chronicrisk factors. These results suggest that the vessels have active PROTECTIVE mechanismsagainst disease development. We also predict that the signaling pathways linked tothis gene may be used therapeutically to activate our natural defense mechanisms.Separate projects are available for Honours to:a. determine the MOLECULAR MECHANISM mediating this protection.b. determine the ROLE of the gene in human healthc. determine whether we can MANIPULATE the pathways to alter disease.

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DR JESSAMY TIFFENMelanoma ProgramEmail: [email protected]: 02 9565 6226

TARGETING EZH2 IN MELANOMA ◊Australia has the highest incidence of melanoma in the world. More than 12,500 new cases of melanoma are diagnosed in Australia every year and 1500 die from metastatic melanoma. There is still no long term cure for metastatic melanoma as not all patients respond to current treatments and the development of drug resistance is a major problem.

Our lab has identified the epigentic modifier EZH2 is abnormally activated in about one quarter of Australian melanoma patients and pre-clinical inhibitors of EZH2 show great promise. We seek to test these inhibitors in vitro and in vivo melanoma models to understand how they work and identify suitable candidate patients.We also seek to understand EZH2 biology and how abnormal EZH2 contributes to melanoma progression, particularly by repression of the anti-tumour immune response. This will be aided by our large collection of patient material from the Melanoma Institute Australia’s bio-specimen bank and cell lines.You will learn the relevant skills necessary for a successful career in science with hands on supervision and daily guidance from our experienced post-docs. You will publish your work in high impact factor journals.

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Where is the Centenary Institute?

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Where is the Centenary Institute?

OUR OFFICIAL ADDRESS IS ADDRESS: Building 93, RPA Hospital

Missenden Road Camperdown 2050

BUT THE EASIEST WAY TO FIND US IS:

Follow Johns Hopkins Drive, off Missenden RoadOr, walk through the uni, we’re next to the Charles Perkins Centre

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www.centenary.org.au 1800 677 977

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