Crystallographic Studies Of Non-canonical Peptides Binding To MHC Class I Molecules.
Funder
National Health and Medical Research Council
Funding Amount
$489,750.00
Summary
Virus infected cells and cancer cells are recognised and eliminated from our body by specialised cells called T-cell lymphocytes. This recognition process is the key step in the immune response and some fundamental questions in immunology are centred on the nature of this process. At the molecular level, the recognition is mediated by the specific interaction between proteins on the surface of the cells. On the T-cell lymphocyte, the T-cell receptor (TCR) binds specifically to a protein called t ....Virus infected cells and cancer cells are recognised and eliminated from our body by specialised cells called T-cell lymphocytes. This recognition process is the key step in the immune response and some fundamental questions in immunology are centred on the nature of this process. At the molecular level, the recognition is mediated by the specific interaction between proteins on the surface of the cells. On the T-cell lymphocyte, the T-cell receptor (TCR) binds specifically to a protein called the MHC on the surface of the target cell. The target cell can be a cancer cell, or an infected antigen presenting cell (specialised cells in the body which present protein fragments (peptides) on their surface via MHC). The structure of a TCR and TCR-MHC have been solved in terms of the shape of the molecules at atomic resolution, bringing detailed information on how these two proteins interact with each other. In this proposal the structural basis of antigen presentation and recognition in cell-mediated immunity will be determined by three-dimensional structures of different peptides on MHC by x-ray crystallography. Cell surface antigen presentation by MHC molecules is crucial for initiating the cellular immune response against invading pathogens and cancer. This proposal encompasses a combined biochemical, immunological, and biophysical approach to understand the range of ligands which can bind to MHC which are subsequently recognised by the TCR. To understand the antigenic properties of modified peptides at the structure level, the x-ray structure of MHC with modified bound synthetic peptides will be determined.Read moreRead less
The Role Of Non-classical MHC Class I Molecules In Adaptive Immunity
Funder
National Health and Medical Research Council
Funding Amount
$443,834.00
Summary
Specialised proteins called MHC class Ia molecules (MHC-Ia) stimulate killer T cells to lyse virus infected cells. In contrast, the function of the closely related MHC-Ib is uncertain. Recent findings have demonstrated that MHC-Ib can also be recognised by T cells and this interaction is important in the control of viral infections. However, despite the similarity to MHC-Ia, it is unclear how this interaction occurs. This project aims to investigate how killer T cells recognise MHC-Ib molecules.
I am interested in determining the molecular basis of immune recognition of foreign and self-antigens in the context of viral, tumor and auto-immunity as well as transplantation. In addition to fundamental observations this knowledge is also applied in va
NKT cells are a type of lymphocyte with the ability to prevent a broad range of diseases including cancer, autoimmunity, infection and graft rejection. Sometimes, NKT cells also cause diseases, including allergy and atherosclerosis. Therefore, the ability to modulate these cells an important health objective. This project will investigate how NKT cells become activated by studying their surface receptors and what these receptors interact with.
Structural Characterisation Of Peptide Bound HLA-DQ2, HLA-DQ8, And Their Specific T Cell Receptors In Celiac Disease
Funder
National Health and Medical Research Council
Funding Amount
$33,626.00
Summary
Celiac disease is an inflammatory condition resulting from an inappropriate immune response to dietary gluten, present in cereals such as wheat, rye and barley. In affected individuals, ingestion of gluten can result in bloating, chronic diarrhoea, and malabsorption. At present, the only treatment is strict adherence to a gluten free diet. This project will investigate the immune response to gluten on a molecular level, aiding in the development of new treatments(e.g. non-toxic wheat varieties).
Structural Investigation Of The Major Histocompatibility Complex Class I Peptide-loading Complex
Funder
National Health and Medical Research Council
Funding Amount
$292,639.00
Summary
The identification and destruction of diseased cells by our immune system is essential to controlling the spread of infection. This proposal is aimed at the characterisation of the peptide-loading complex (PLC), a large molecular machine that facilitates a crucial step in the process of ‘flagging’ infected cells. Determining the 3D structures of its key components, as well the way in which they interact will help us understand how the PLC contributes to maintaining our body’s health.
I am an immunologist with a background in virology and peptide chemistry and my work is therefore inter-disciplinary but focused on the design of synthetic, epitope-based vaccines against infectious agents particularly influenza and hepatitis C viruses an