The Regulatory Role Of Clec12A In Antigen Presentation And Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,381,077.00
Summary
The immune system maintains a balance between initiating immune responses to infections and suppressing immune responses in health. We have identified, on the surface of specialised immune cells, a protein that is critical for regulating immune responses and dampening down inflammation. This proposal aims to determine how this protein functions in health and under inflammatory conditions, and to develop approaches based on its molecular interactions to reduce inflammatory disease.
Molecular Basis For The Efficient Processing Of Antigens Taken Up By Clec9A, A DAMP Receptor On Dendritic Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,302,392.00
Summary
Dendritic cells (DC) of the immune system utilise specific receptors to sense danger signals from their environment. We identified a DC danger receptor, Clec9A, which recognizes and induces immunity to “dangerous” dead cells eg. infected cells or killed tumour cells. We will investigate how DC use Clec9A to process “dangerous” dead cells, and the factors that control the potency of this immune response. This will enable us to develop novel immunotherapies for infectious diseases and cancer.
Enhancing Vaccine Efficacy By Harnessing Dendritic Cell Receptors And Their Unique Properties
Funder
National Health and Medical Research Council
Funding Amount
$687,519.00
Summary
Potent vaccination might be achieved by using monoclonal antibodies as magic bullets to target vaccines to special cells in the body. We show that targeting these special cells by using monoclonal antibodies that recognise Clec9A is effective, perhaps because it brings several different immune cells together so that they orchestrate very efficient immune responses. This application investigates how targeting Clec9A allows strong vaccination so that we can apply this to new generation vaccines.
Molecular Characterisation Of The Dendritic Cell Receptor Clec9a And Its Ligand Interactions
Funder
National Health and Medical Research Council
Funding Amount
$651,784.00
Summary
The immune system senses danger from infectious diseases, damaged and dead cells. We identified a danger receptor, Clec9A, on a specialised cell type of the immune system in mice and humans. Clec9A recognizes and induces immunity to dangerous dead cells. Delivering vaccines to Clec9A improves vaccine responses. We will investigate how Clec9A recognises and reacts to danger, and how we can mimic this recognition to improve vaccine design.
The Structure And Composition Of The T-cell Receptor-CD3 Complex
Funder
National Health and Medical Research Council
Funding Amount
$434,644.00
Summary
Our research will provide a fundamental advance in our understanding of how foreign viruses and pathogens trigger the immune system. Gaining a greater understanding of these central events will facilitate the design of novel therapies to treat immune associated disorders such as transplant rejection, autoimmune disease and some cancers.
Mechanism Of Epidermal Growth Factor Receptor Transactivation
Funder
National Health and Medical Research Council
Funding Amount
$578,268.00
Summary
This application examines the cellular events that control heart growth in response to angiotensin, a hormone linked to heart failure. We believe that the same cell processes are also involved in cancer cell growth and by understanding the mechanism by which angiotensin promotes growth, better therapies against human cardiovascular disease and its relationship to uncontrolled growth will evolve.
Regulation Of The Signalling Efficiency Of The T Cell Antigen Receptor
Funder
National Health and Medical Research Council
Funding Amount
$456,557.00
Summary
An immune response starts with activation of the T cell antigen receptor (TCR). How T cell receptor signalling begins, however, is not well understood. We have developed a novel imaging approach that allows us to directly observe what happens after an antigen binds to the receptor. The research will provide mechanistic insights into how T cells sense and discriminate antigens. This knowledge will aid the development of cancer immunotherapies and vaccines.
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. This project will investigate how NKT cells become activated in these diseases by studying their surface receptors and what these receptors interact with.
Characterisation And Development Of Type-2 NKT Cells
Funder
National Health and Medical Research Council
Funding Amount
$853,885.00
Summary
Humans defend themselves from foreign pathogens by mounting a protective immune response. Type-2 NKT cells recognise foreign lipid molecules and play a key role in immunity. This project is designed to understand to how Type-2 NKT cells develop within the body, how they recognise lipid molecules and how they carry out their immune functions. This work will have important implications in understanding the role of NKT cells in human health and disease.
Recognition Of Lipid Antigens By CD1d-restricted Type-2 NKT Cells
Funder
National Health and Medical Research Council
Funding Amount
$417,684.00
Summary
Protection against infection depends on T cells, which recognise and target foreign molecules called antigens via a specialized antigen receptor known as a T cell receptor (TCR). This project focuses on a specialised population of T cells called Natural Killer T (NKT) cells that recognise lipid antigens. The work outlined in this grant will increase our understanding of how different TCRs can recognise diverse lipid antigens thus providing insight into the role of NKT cells in the immune system.