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
Harnessing Systems Biology By Integrating Proteomics And Immunopeptidomics To Understand Prostate Cancer Carcinogenesis, Diagnosis And Treatment
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
This ECF proposal aims to systematic profile to proteomic compositions of prostate normal, and cancer cells, and utilise such data to develop innovative systems biology models that will enable accurate prediction of tumour associate antigen (TAA) presentation for both aggressive and nonaggressive prostate cancer. The outcomes of this project will generate urgently needed knowledge for understanding TAA presentation and contribute to identification of tractable targets for vaccine development.
Quantification Of Antigen Presentation To CD8 T Cells During Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$582,072.00
Summary
Knowledge of how virus-infected cells are detected by the bodyÍs immune system is fundamental to our understanding of virus infections and attempts to improve vaccines. We know that many proteins are displayed during virus infection but until now, the precise details of this display have only been worked out for very few proteins, studied one at a time. In this project we will apply cutting-edge technology to gain the first holistic view of how a virus-infected cell looks to the immune system.
Tracking Endogenous Presentation Of MHC Class-II-Restricted Viral Epitopes
Funder
National Health and Medical Research Council
Funding Amount
$165,436.00
Summary
CD4+ T cells play an important role in controlling viral infections. Proteins from viruses are processed into small pieces by immune stimulating cells and these are then displayed on special molecules of the immune stimulating cells for the CD4+ T cells to recognise and respond to. This project aims to establish the various pathways by which the immune stimulating cells process the proteins and present them to the CD4+ T cells.
Characterisation Of An Antigen Presenting Cell Unique To Spleen
Funder
National Health and Medical Research Council
Funding Amount
$420,606.00
Summary
The body depends on a range of defence mechanisms to remove invaders that enter by various routes. Antigen presenting cells are central to immunity in that they engulf and destroy dead cells and pathogens and present pieces of those pathogens or 'antigens' to white blood cells called T and B lymphocytes. These cells then start to fight the infection or disease. A new type of antigen presenting cell will be investigated for its particular ability to arrest blood-borne pathogens and disease.
Unraveling The Link Between HLA B27 And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$746,102.00
Summary
Ankylosing spondylitis and related diseases cause significant morbidity in up to 0.25% of the population. Current treatments have limited efficacy and often debilitating side effects. More targeted peptide antigen based therapies will have fewer side effects and would be of major clinical importance to this group of diseases. This project seeks to identify peptide antigens that could be used in targeted immunotherapy. We also seek to understand how some of the idiosyncratic properties of HLA B27
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
T-cells: The Key To Unlocking Immunity Against Aggressive Lymphoma
Funder
National Health and Medical Research Council
Funding Amount
$322,951.00
Summary
By investigating several aspects of patients’ immune defenses against the cancer cells in Diffuse large B-cell lymphoma, this project will provide critical insights on ways to harness the patient’s own immune system to effectively mount anti-tumour responses. These results will pave the way for future therapeutic strategies to successfully treat and prevent lymphoma.
The Genetics Controlling The Course Of Herpesvirus Infection In Humans
Funder
National Health and Medical Research Council
Funding Amount
$69,684.00
Summary
Epstein-Barr Virus and Human Cytomegalovirus are common viruses present in more than 50% of the adult population. They have a major impact on the human immune system, stimulating large numbers of T cells that are essential to control the persistent viral infection. Generally, these viruses cause few problems; however, an unfortunate minority suffer major life threatening clinical problems. There has also been some evidence for a role of EBV infection in the pathogenesis of Multiple Sclerosis.
Biochemistry And Cell Biology Of Antigen Presentation And T Cell Activation
Funder
National Health and Medical Research Council
Funding Amount
$763,409.00
Summary
José Villadangos studies the cells and molecules involved in Antigen Presentation. This phenomenon consists of the detection, capture and display of microbe fragments on the surface of Antigen Presenting Cells (APC) for recognition by T cells. This initiates an immune response that culminates in the deployment of cells and molecules armed to fight the infection. His research may lead to development of more effective vaccines and prevention of autoimmunity, allergy and transplant rejection.