At least 6 young Australians are diagnosed each day with type 1 diabetes. This Program aims to change the way type 1 diabetes is managed by proactively treating its underlying mechanisms. We will develop safer and more effective immune therapies, develop islet transplantation, look for better markers of disease, and identify ways to preserve insulin-producing cells. The Program aims to propel type 1 diabetes research forward to reach the goals of prevention and cure.
The Molecular Determinants Of Immunological Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$473,477.00
Summary
Autoimmune diseases, such as type I diabetes and multiple sclerosis, are debilitating disorders that impose a massive toll on wellbeing in Australia and worldwide. This fellowship will support research aimed at determining the genes and mechanisms that control autoimmunity. New technologies will be brought to bear to track immune cells throughout their development, maturity and malfunction in disease settings. We aim to uncover new therapeutic targets to prevent and reverse autoimmune disease.
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 Susceptibility Genes And Microbiota In Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$303,924.00
Summary
Utilising my background in Immunology I will investigate whether specific genetic mutations can create a susceptibility for dysregulation of the flora and immune system within the gut, thus predisposing an individual to inflammatory bowel diseases (ulcerative colitis and Crohn's disease) as well as non-intestinal inflammatory conditions. These diseases are becoming an increasingly prevalent and serious health burden in Australia. We aim to use this knowledge in order to design specific treatment ....Utilising my background in Immunology I will investigate whether specific genetic mutations can create a susceptibility for dysregulation of the flora and immune system within the gut, thus predisposing an individual to inflammatory bowel diseases (ulcerative colitis and Crohn's disease) as well as non-intestinal inflammatory conditions. These diseases are becoming an increasingly prevalent and serious health burden in Australia. We aim to use this knowledge in order to design specific treatments for these diseases.Read moreRead less
The Control Of Autoimmunity Originating From Somatically Hypermutated B Cells
Funder
National Health and Medical Research Council
Funding Amount
$530,337.00
Summary
Our immune systems are capable of producing long-lived antibodies that can last a lifetime. Sometimes, this powerful process can however become abnormal and result in autoimmune diseases such as lupus. We have recently developed the first experimental mouse model that allows researchers to study this process in great detail. This funding will extend our initial observations by identifying the exact mechanisms by which important regulators of autoimmune disease act.
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.
How Deletional And Non-Deletional Tolerance Mechanisms Integrate To Prevent Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$509,944.00
Summary
The body produces millions of immune cells every day to fight infection. Some of these immune cells are defective and dangerous because they can cause autoimmune diseases, like Type I diabetes and multiple sclerosis. To defuse this risk, such immune cells are either caused to die or are inactivated to prevent autoimmunity. We propose to investigate how the processes of immune cell death and inactivation work in health and disease so we may harness these mechanisms to cure autoimmunity.
Understanding The Pathogenesis And Heterogeneity Of Autoimmunity As Failure Of Multiple Steps
Funder
National Health and Medical Research Council
Funding Amount
$504,023.00
Summary
Autoimmune diseases like diabetes, thyroid disease or rheumatoid arthritis affect around 1 in 15 people in Australia. It is clear that defects in a number of different genetic mechanisms can contribute to the development of autoimmunity. But it is currently not clear how these different mechanisms need to interact to prevent the onset of disease. This grant seeks to understand these interactions and how defects in two or more tolerance mechanisms can lead to autoimmunity.