Experimental Medicine

Head of Discipline
Professor A Basten
Location
University of Sydney

The Discipline (also known as the Centenary Institute) specialises in molecular biology and immunology and their application to a range of common conditions including infections, autoimmune disorders, allergy, cancer, and cardiovascular disease. Close links exist with the immunology section of the Disciplines of Medicine and Infectious Diseases headed by Professor Britton and the Department of Clinical Immunology at Royal Prince Alfred Hospital.

The Discipline is located in a new state-of-the-art research building on the campus of Royal Prince Alfred Hospital adjacent to the Blackburn Building. It is fully equipped for modern cellular and molecular research and provides centralised facilities in flow cytometry and for generation of transgenic models, monoclonal antibody production, computer network (including bioinformatics) and library.

The Discipline occupies a new state-of-the-art research building on the campus of Royal Prince Alfred Hospital adjacent to the Blackburn Building.

The Discipline occupies a new state-of-the-art research building on the campus of Royal Prince Alfred Hospital adjacent to the Blackburn Building. It is fully equipped for modern cellular and molecular research with its own laboratory facilities, lecture theatre and computer network. Strong links exist with clinical departments at Royal Prince Alfred Hospital.

Director's Laboratory incorporating the B Cell Biology Group
Scientists: Tony Basten (Group Leader); Robert Brink, Chris Jolly, and Stuart Tangye (Research Fellows and lab heads); Pablo Silveira and Didrik Paus (Postdoctoral Research Fellows); Daniel Sze and Joy Ho (collaborating scientists, Institute of Haematology, RPAH).

Use of transgenic and knockout (KO) mice for studying:

• self tolerance and autoimmunity in the B cell compartment
• pathogenesis of experimental models of human diseases including type 1 diabetes (Basten, Brink)

Study of somatic hypermutation of antibody genes in transgenic mice and cell lines with the aim of understanding how this unique process occurs and its role in cancer (Jolly).

Signal transduction through the TNF receptor superfamily including function of TRAF2 in health and disease (Brink).

These studies utilise a combination of cellular biology, molecular biology and protein biochemistry to investigate cell behaviour in vitro as well as intracellular signalling.

Gene Therapy Research Laboratory
Scientists: John Rasko (Group Leader); Charles Bailey, Fiona Battah and David Lu (Postdoctoral Research Fellows)

Focus on mechanisms of improving the efficiency of gene delivery to cells with particular emphasis on:

• Retroviral receptors recently cloned by us
• Novel retrovirus packaging cell lines
• Monoclonal antibodies to characterise cell subsets
• Embryonic and adult stem cells, particularly haemopoietic stem cells
• Novel retroviral receptors
• CTCF and Boris transcription factors.

Liver Immunology Laboratory
Scientists: Geoff McCaughan (Group Leader); Alex Bishop (Clinical Research Lecturer); Mark Gorrell (Senior Research Fellow); Patrick Bertolino, Heather Knott and Devanshi Seth (Postdoctoral Research Fellows)

• Studies of liver transplant tolerance and rejection:
  - In animal models examining high dose activation
  - To investigate a novel mechanism of transplant tolerance
  - In transplant patients by monitoring the immune system
• Immunopathogenesis of cirrhosis and Hepatitis C infection
• Biochemistry and biological roles of the dipeptidyl peptidase IV (DP-IV/CD 26/ADAbp) gene family in T-cell proliferation, cancer growth and the pathogenesis of cirrhosis
• Use of transgenic mice to investigate immune mechanisms of liver damage
• Role of the liver in oral tolerance.

Molecular Cardiology Laboratory
Scientists: Christopher Semsarian (Group Leader)

The main focus of the laboratory is the study of heart muscle disorders, and in particular those diseases which are caused by genetic defects. A specific focus is on hypertrophic cardiomyopathy, an inherited cardiac disorder which is the commonest cause of sudden death in people aged less than 35 years.

Particular areas of research include:

• transgenic mouse models of inherited heart disorders
• human genetic studies in hypertrophic cardiomyopathy
• studies in genetic and environmental modifiers of cardiac disease
• cellular studies to determine signalling mechanisms in cardiac hypertrophy

Mycobacterial Laboratory
Scientists: Warwick Britton (Group Leader); Helen Briscoe (Senior Lecturer); Bernadette Saunders, James Triccas and Grant Shoebridge (Postdoctoral Research Fellows)

Study of immune responses in tuberculosis and leprosy with the focus on:

• The protective efficacy of novel DNA and other vaccines against tuberculosis
• Cytokine requirement for protection against tuberculosis, utilising gene deficient mice (e.g. TNF / lymphotoxin family gene knockout mice)
• Parallel studies on human T-cell responses to mycobacteria to help define immunological correlates of protective immunity for future vaccine trials
• DNA vaccines against leprosy and M. avium infection using genes we have previously cloned and tested in collaboration with a field laboratory in Nepal
• Effect of BCG immunisation on atopy and asthma
• Mycobacterial gene expression
• Development and assessment of attenuated M. tuberculosis and BCG strains for vaccination.

T-cell Biology Laboratory
Scientists: Barbara Fazekas de St Groth (Group Leader); Carl Power, Adrian Smith, Elena Chklovskaia and Nabila Seddiki (Postdoctoral Research Fellows)

• Use of transgenic and gene knockout mice for studying:
  - self tolerance and autoimmunity in the T-cell compartment
  - dendritic cell control of the decision between tolerance and immunity
  - tolerance and rejection of tissue transplants;
• Research into the pathogenesis of autoimmune inflammatory bowel disease in mice and humans
• Role of microorganisms in regulating the immune system ('the hygiene hypothesis')
• Use of dendritic cell immunotherapy in animal models and cancer patients

Multidrug Resistance Laboratory
Scientists: John Allen (Group Leader)

Programme in molecular basis of multidrug resistance in cancer. The Laboratory performs basic research that is relevant to cancer chemotherapy. Current projects and areas of interest include:

• Interactions of new anticancer drugs with multidrug transporter proteins
• Role of drug transport in the pharmacokinetics and toxicity of irinotecan and other cytotoxic drugs
• Functional consequences of ethnic differences in single nucleotide polymorphisms of multidrug resistance genes
• The role of defective apoptosis pathways in drug resistance of malignant melanoma, using transgenic and KO mouse models

Professor A Basten
Head of Discipline

Blackburn Building, D06
University of Sydney
NSW 2006 Australia

Phone: +61 2 9565 6135
Fax: +61 2 9565 6111
E-mail: