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Dr Ed Bertram

Immunogenomics Group

Head, Scientific Programs
Australian Phenomics Facility
Building 117 Garran Road

T: +61 2 6125 1328
M: 0419 263616
F: +61 2 6125 1381
E: Edward.Bertram@anu.edu.au

Mail Address:
The John Curtin School of Medical Research
Building 54
The Australian National University
Canberra ACT 0200 Australia

 

• Publications
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Cell-Mediated Immunogenomics Laboratory

T cell activation and the Immune Response to Infection

My laboratory, which works within the Immunogenomics Group, is involved in elucidating the genes and mechanisms involved in cell mediated immunity. Understanding the genetic basis for cell mediated immunity will lead to advances in vaccine design for a range of infectious diseases including HIV, Malaria, and Tuberculosis.
T cells, via their antigen specific T cell receptor recognize antigen in the form of a peptide, bound to a major histocompatibility complex protein on the surface of the antigen presenting cell. For a T cell to be activated it must integrate signals from both the TCR as well as from additional costimulatory receptors. My lab is studying the role of costimulatory molecules and intracellular proteins involved in activation of T cells and the role these molecules play in vivo during the immune responses to viral infection.
Resting T cells express a protein called CD28 that binds to ligands, B7-1 or B7-2 on antigen presenting cells thereby providing costimulatory signals for T cell activation. After activation, T cells begin to express additional costimulatory receptors and these may function to amplify, diversify and sustain the T cell response. One example is 4-1BB that is a stimulatory member of the TNF receptor family and is found on activated CD4 and CD8 T cells. Its ligand, 4-1BBL is found on activated antigen presenting cells and can provide a CD28-independent costimulatory signal leading to cytokine production, proliferation and development of cytotoxic effector function by T cells.

1. Using a combination of knockout and transgenic mouse models we are currently studying the role of costimulatory receptors/ligand interactions between 4-1BB:4-1BBL, HVEM:LIGHT and CD28:B7.1/B7.2. By following expansion of T cells during immune responses to infectious agents in wildtype mice compared to mice lacking particular costimulatory pathways, we are trying to delineate the role of these molecules in specific phases of the immune response.
   
2. Using ENU-gene variant mice we are studying the role of specific domains of proteins involved in integrating T cell receptor and costimulatory signals. Currently this includes CARMA-1, ZAP-70, NFkB2. In addition we are also investigating the role of STAT-1 in T cell responses to infectious disease and auto-immunity.
   
3. My laboratory is screening random ENU gene-variant mouse libraries in a genome to phenome discovery project at the Australian Phenomics Facility funded by the NIH. This screen will detect unknown genes and mechanisms involved in T cell activation and cell-mediated immunity, in particular Ag-specific CD8 T cell memory and recall responses to viral infection.

Collaborators:

Professor Tania Watts, University of Toronto, Canada
Dr Jennifer Cannons, National Institutes of Health, USA
Dr Stephen Turner, University of Melbourne
Professor Peter Doherty, University of Melbourne
Dr David Willenborg, The Canberra Hospital
Dr Michael Beard, University of Adelaide
Dr Guna Karupiah, JCSMR
Prof Ian Ramshaw, JCSMR

NIH Genes for Immunity and Tolerance Consortium Collaborators:

University of California San Francisco
Drs Lewis Lanier, Art Weiss, Jason Cyster and Susan Watson