I am a Clinical Immunologist, Immunopathologist, clinical researcher and laboratory scientist exploring the interactions between T cell and viral infections. My area of particular interest is the mechanisms by which HIV infection subverts effective T cel
The Genetics Governing The Specificity Of T Cell Receptors For Peptide-MHC
Funder
National Health and Medical Research Council
Funding Amount
$303,828.00
Summary
T lymphocytes play a pivotal role in the immune system by recognising virus-infected tissue through the use of highly specific cell surface receptors. These T cell receptors (TCR) recognise viral peptides (p) presented by MHC molecules on the surface of virus-infected cells. For a TCR to be successfully triggered, it must lock onto an exact 3-dimentional pMHC match. In this way, any given TCR must simultaneously recognise both the viral peptide and the MHC presenting it. Such recognition must be ....T lymphocytes play a pivotal role in the immune system by recognising virus-infected tissue through the use of highly specific cell surface receptors. These T cell receptors (TCR) recognise viral peptides (p) presented by MHC molecules on the surface of virus-infected cells. For a TCR to be successfully triggered, it must lock onto an exact 3-dimentional pMHC match. In this way, any given TCR must simultaneously recognise both the viral peptide and the MHC presenting it. Such recognition must be sensitive and precise since a false positive could result in destruction of healthy tissue. There are a huge variety of TCRs and pMHCs, but there are only a few examples where the precise molecular interactions within the TCR-pMHC complex are known. Surprisingly, these studies have shown very limited consistency in the way the TCRs bind the pMHCs and therefore, the structural rules that underlie why TCRs consistently bind MHC remains a mystery of critical importance to this fundamental feature of the immune system. In this proposal, we will attempt to elucidate the rules of TCR-pMHC engagement. Another question to be addressed in this proposal is: During a viral infection, why are certain TCRs chosen above others that also have the capacity to recognise the same viral peptide? By investigating exactly which feature-s of these receptors predisposes their supremacy, we may be better able to predict the outcome of a pathogen attack and to even one day build our own super receptors. Finally, this proposal will also investigate how natural mutations in TCR genes across the human population affect our individual responses to viruses. Overall, advances in each of these core areas of medical research will aid in the development of new intelligent vaccines and individualised drugs for the treatment of cancer and infectious disease.Read moreRead less
Investigations Into The Biology And Functionality Of The Human T Cell Receptor
Funder
National Health and Medical Research Council
Funding Amount
$424,262.00
Summary
T lymphocytes play a pivotal role in the immune system by recognising virus-infected tissue and tumour cells through the use of specific cell surface receptors called T cell receptors (TCR). This project will study why partcular TCRs are used by the immune system, and will also examine the specificity of T cell recognition by determine the range of molecules an individual T cell can recognise. The work will aid in the development of new intelligent vaccines for cancer and infectious disease.
Interactions Between Adaptable Pathogens, Drugs And The Human Host
Funder
National Health and Medical Research Council
Funding Amount
$5,727,327.00
Summary
The Centre for Clinical Immunology and Biomedical Statistics (CCIBS) represents a collaboration between Royal Perth Hospital and Murdoch University that has brought together internationally recognised expertise in clinical immunology, experimental biology and innovation in biostatistics and computing. These resources have been applied to a broad range of research issues within the broad framework of HIV and hepatitis C disease and treatment. CCIBS has become a leading centre of research excellen ....The Centre for Clinical Immunology and Biomedical Statistics (CCIBS) represents a collaboration between Royal Perth Hospital and Murdoch University that has brought together internationally recognised expertise in clinical immunology, experimental biology and innovation in biostatistics and computing. These resources have been applied to a broad range of research issues within the broad framework of HIV and hepatitis C disease and treatment. CCIBS has become a leading centre of research excellence internationally, establishing a reputation for innovative approaches to host-viral interactions that are built on a long tradition of research into the population genetics of both human and viral genomes, combined with a willingness to negotiate complex computation and statistical challenges in order to faithfully reflect dynamic biological processes at a population level. An early recognition that large and integrated repositories of genetic and clinical data are fundamental to the research success in the genomic era has also led to the creation of the single most comprehensive repository of HIV genetic sequencing data in the world. The contributions that CCIBS has made to several distinct areas of research, including understanding viral adaptation to host immune responses, the development of genetic testing to predict drug hypersensitivity reactions, and causes of antiretroviral drug-associated toxicities, have been published in prestigious journals including Science, Nature, Nature Immunology, The Lancet, Proceedings of National Academy of Sciences, and The American Journal of Human Genetics, and have also resulted in numerous international collaborations that recognise the unique attributes that CCIBS has been able to bring to the global research effort aimed at understanding fundamental aspects of HIV and hepatitis C biology and treatment.Read moreRead less