Prevention Of Autoimmune Diabetes By Immune Tolerance To Proinsulin
Funder
National Health and Medical Research Council
Funding Amount
$504,597.00
Summary
In type 1 diabetes, insulin is the first target of the immune system. Strategies to prevent the immune system targeting insulin in mice early in the disease process work, but it is not clear if such strategies would be effective if applied late. This is important because preventive therapies for human type 1 diabetes are currently feasible only late in the disease process. We aim to address this by removing T cells specific for insulin at different stages of the disease.
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.
De Novo Mutations And The Pathogenesis Of Childhood-onset Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,406,510.00
Summary
This project aims to reveal the gene abnormalities that cause devastating autoimmune diseases to develop in some children, such as Type 1 diabetes, juvenile arthritis and autoimmune destruction of blood cells. The project will use new technologies to identify alterations in the DNA sequence of a child compared to either of their parents, and to test suspicious DNA alterations in laboratory mice in order to understand the gene effects and evaluate new treatments.
Analysis Of Human CD4+ T-cell Responses To Epitopes Formed By Peptide Fusion In The Pathogenesis Of Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$1,239,989.00
Summary
Type 1 diabetes is caused by immune-mediated destruction of the insulin-secreting beta cells. Recently we discovered new targets ‘seen’ by the immune system that may explain why the immune system causes type 1 diabetes. Here we will determine if responses to these targets cause type 1 diabetes. This is important because it tests a new idea and our results will have a major impact on efforts to develop new therapies for type 1 diabetes an other autoimmune diseases.
The Role Of The T Cell Protein Tyrosine Phosphatase In Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$654,725.00
Summary
Autoimmune diseases such as type 1 diabetes, Crohns disease & rheumatoid arthritis collectively affect ~5% of Australians & are associated with the immune system attacking the body’s organs as if they were a foreign infection. Genetic studies in humans & animal studies point towards the enzyme TCPTP being important in the prevention of autoimmunity. This proposal will define the molecular & cellular pathways by which TCPTP prevents autoimmunity.
The Molecular Basis Of Human CD4+ T-cell Responses In Autoimmune Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$656,498.00
Summary
Over 120,000 Australians currently suffer from type 1 diabetes. This incurable disease typically strikes in childhood or adolescence and is caused by the immune system destroying the cells which make insulin. This project aims to determine how and why the insulin producing cells are recognized by the immune system. Eventually this work will lead to new vacccines to prevent the immune system from destroying the insulin producing cells.
The Role Of Interleukin-21 In The Pathogenesis Of Autoimmune Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$519,000.00
Summary
T cells are a component of our blood (white blood cells) and a major component of the body's defense system against infection, known as immunity. Without T cells, we would fail to resist infection by foreign agents, such as viruses, bacteria and fungi. Autoimmune (type 1) diabetes is a disease in which T cells attack our own pancreatic islet self tissues as if they were foreign. T cells that react against the islets of the pancreas cause destruction of the insulin producing beta cells so that th ....T cells are a component of our blood (white blood cells) and a major component of the body's defense system against infection, known as immunity. Without T cells, we would fail to resist infection by foreign agents, such as viruses, bacteria and fungi. Autoimmune (type 1) diabetes is a disease in which T cells attack our own pancreatic islet self tissues as if they were foreign. T cells that react against the islets of the pancreas cause destruction of the insulin producing beta cells so that the pancreas can no longer make insulin. Diabetes is a life-threatening disease because insulin is a hormone that enables people to get energy from food. Type 1 diabetes is usually diagnosed in childhood and insulin must be administered daily by injection or through a pump in order to survive. Unfortunately, taking insulin doesn t cure diabetes and people continue to suffer from an extensive list of complications affecting most vital organs. Interleukin-21 (IL-21) is a soluble protein that is produced by cells enabling them to communicate with other cells. IL-21 helps cells to produce factors that cause inflammation and assist in clearance of viruses and bacteria from the body. However, our studies show that IL-21 is a major factor in the development of the T cells that destroy beta cells and cause diabetes. Our studies show that IL-21 is over-expressed in an important murine model of spontaneous type-1 diabetes. We have isolated the T cells that cause diabetes and show that they are distinguished from other T cells by very high levels of the receptor for IL-21. This project focuses on the IL-21-responsive T cells that cause diabetes and aims to determine the mechanisms by which the cytokine IL-21 causes destructive immune responses and ways to modulate its production. This project applies basic science to the important public health issue of type 1 diabetes for the development of therapeutic intervention strategies.Read moreRead less
The Role Of MHC Class I Expression On Pancreatic Ductal Lineage Cells In The Pathogenesis Of Type I Diabetes (TID).
Funder
National Health and Medical Research Council
Funding Amount
$484,300.00
Summary
MHC molecules act as traffic lights to the immune system telling it whether to stop or go, so that only when there is an infection does the immune system receive the signal to destroy target cells. However, the immune system in Type 1 Diabetes patients receives signals to destroy the insulin-producing cells when there is no apparent infection. We aim to determine where the faulty traffic signal occurs and so be in a better position to design intervention strategies to prevent Type 1 Diabetes.