The Role Of Self Reactive T Cells In The Normal TCR Repertoire
Funder
National Health and Medical Research Council
Funding Amount
$363,601.00
Summary
The immune system is highly regulated and sophisticated in order to distinguish foreign invaders from our own body. Once control is lost in this system, mistakes can happen, and autoimmunity, attack of ones self may result. Surprisingly potentially dangerous ‘fighter’ T cells can be readily found in healthy individuals whom are free from autoimmunity. The aim of this project is to understand how we can survive with these potentially harmful T cells around and what may activate them.
My research is directed to the prevention of diabetes, across the spectrum from type 1 to type 2 diabetes. It is based on understanding immune-inflammatory mechanisms that contribute to dysfunction and death of pancreatic insulin-secreting beta cells and tissue resistance to the action of insulin. I study these mechanisms in rodent models and in humans in the context of relevant environmental factors and genes, with the aim of manipulating them for therapeutic benefit.
Immune Tolerance In Experimental Autoimmune Encephalomyelitis Following Transplant Of Bone Marrow Cells Genetically Encoding Autoantigen
Funder
National Health and Medical Research Council
Funding Amount
$339,143.00
Summary
Autoimmune diseases affect 5-6% of the population and include diseases such as multiple sclerosis. Our studies focus on examining a gene therapy approach together with bone marrow transplantation to treating autoimmune diseases. Using a model for multiple sclerosis we are finding promising results
My research is directed to the prevention of type 1 diabetes, based on understanding immune-inflammatory mechanisms that contribute to dysfunction of insulin-secreting beta cells and tissue resistance to the action of insulin. I study these mechanisms in rodent models and in humans with the aim of manipulating them for therapeutic benefit. I am particularly interested in understanding environment-gene interactions mediated by epigenetic modifications.
MicroRNA Networks That Safeguard The Functional Program Of Regulatory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$457,941.00
Summary
A newly discovered group of molecules termed microRNAs are thought to function as rheostats for the activity of genes. We have shown that these molecules are critical for the function of an immune cell type termed regulatory T cells. Without these cells, the immune system is unable to prevent uncontrolled and destructive inflammation. This proposal aims to utilize diverse technologies to uncover the precise molecular mechanisms by which microRNAs safeguard the function of regulatory T cells.
How Does Genetic Variation For Trig Affect Autoimmune Responses Mediated By Toll-like Receptors?
Funder
National Health and Medical Research Council
Funding Amount
$671,114.00
Summary
Juvenile diabetes is an autoimmune disease that affects more than 120,000 Australians. We have recently discovered a novel gene, named Trig, in a genetic study of mice that develop juvenile diabetes similar to children. This research proposal aims to determine the function of Trig in the immune system and how it contributes to the development of autoimmune diseases, such as juvenile diabetes.
Dynamics And Mechanisms Of Immune Complex-mediated Skin Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$526,467.00
Summary
Type III hypersensitivity underlies a number of common autoimmune diseases, including rheumatoid arthritis and lupus erythematosus. These diseases are caused by the deposition of immune complexes (IC) and the accumulation of neutrophils within small blood vessels. We will use real time imaging to dissect in space and time the recruitment of neutrophils and IC deposition during type III hypersensitivity reactions in order to better understand the pathogenesis of these conditions.
Molecular And Cellular Studies Of The Adaptive Immune Response In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$16,509,154.00
Summary
Immune responses protect us against pathogens such as viruses and bacteria. However inappropriate immune responses can result in autoimmune conditions such as systemic lupus erythmatosus, multiple sclerosis, type I diabetes, asthma as well as immunodeficiencies. The aim of our proposal is to gain a thorough understanding of how all the cells of the immune system function and interact with each other, and what goes wrong when inflammatory diseases develop. We plan to do this using state-of-of-the ....Immune responses protect us against pathogens such as viruses and bacteria. However inappropriate immune responses can result in autoimmune conditions such as systemic lupus erythmatosus, multiple sclerosis, type I diabetes, asthma as well as immunodeficiencies. The aim of our proposal is to gain a thorough understanding of how all the cells of the immune system function and interact with each other, and what goes wrong when inflammatory diseases develop. We plan to do this using state-of-of-the-art technologies, including genetically modified mice, gene microarrays, monoclonal antibodies, and flow cytometry. We have brought together Australia's leading immunologists with complimentary expertise and research interests in specific areas of immunology including cytokines, cell migration, inflammatory diseases, autoimmunity and cell-cell interactions. One aspect of the application is to understand the genetic and molecular basis of immunological diseases. However we also wish to move on from an understanding to treatment of immunological diseases through the development of novel therapeutics. We will form collaborations with biotech and pharmaceutical companies (including our own spin off companies) to advance important new therapeutics for autoimmune and allergic diseases. These conditions represent a significant health burden to Australia.Read moreRead less
Understanding The Critical Mechanisms That Govern Regulatory T Cell Life And Death Decisions
Funder
National Health and Medical Research Council
Funding Amount
$338,811.00
Summary
Autoimmune diseases impose an increasingly large health burden. Treg cells prevents the immune system from attacking “self” offering the promise of using these cells to restore immune balance in autoimmune diseases. However, there are currently no protocols that reliably modify Treg cell numbers. This study will elucidate the mechanisms that govern Treg cell survival and death, revealing potential molecular targets to manipulate the quality and quantity of Treg cell for therapeutic benefit.
A new approach to reversing and preventing immune-mediated diseases. Chronic inflammatory diseases affect up to 20 per cent of Australians. These diseases reduce wellbeing and life potential and shorten lifespan. This project addresses the urgent need for effective therapies and focuses on developing strategies for disease cure and prevention.