Thymic Epithelial Cell Apoptosis, Aire And Autoimmune Disease.
Funder
National Health and Medical Research Council
Funding Amount
$470,799.00
Summary
Autoimmune diseases, like diabetes and multiple sclerosis are a significant disease burden. Their root cause is the failure of the immune system to distinguish between the body's own tissues and potential pathogens. We propose to study how potentially dangerous immune cells are destroyed in the thymus before they can develop. This research will significantly improve our understanding of how autoimmune diseases begin.
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.
Regulation Of Autoimmunity By Non-apoptotic Caspases
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Excessive cell death can lead to chronic inflammation and autoimmunity. Cells can die by different mechanisms including necroptosis which causes inflammation, and apoptosis which does not. Recent studies show that caspases, a component of the apoptosis pathway which accelerate cell death, also prevent immune activation by dying cells. I will investigate whether caspases contribute to autoimmune disease and whether caspases can dampen the inflammation that occurs during necroptotic cell death.
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
The team has been at the forefront of research on type 1 diabetes for over a decade. This form of diabetes is a major chronic disease from childhood, as well as accounting for at least 10% of adult-onset diabetes. It occurs when the body�s immune system attacks and destroys the beta cells in the pancreas that make insulin, the hormone that controls the level of glucose in the blood. The team was one of the first in the world, and is the only one in Australia, to develop screening programs to tes ....The team has been at the forefront of research on type 1 diabetes for over a decade. This form of diabetes is a major chronic disease from childhood, as well as accounting for at least 10% of adult-onset diabetes. It occurs when the body�s immune system attacks and destroys the beta cells in the pancreas that make insulin, the hormone that controls the level of glucose in the blood. The team was one of the first in the world, and is the only one in Australia, to develop screening programs to test and identify people at risk for type 1 diabetes. They showed that the underlying disease could start years before symptoms occurred and discovered genes that determine the rate at which the underlying disease progresses. They have also found evidence that the disease may be triggered by gut viruses called rotaviruses in genetically-susceptible individuals. They showed that type 1 diabetes could be prevented in a mouse model by getting the immune system to make a protective response to insulin, and then went on to apply this in at-risk humans in a controlled trial of intranasal insulin, the first of its kind. They have used genetic techniques not only to pinpoint the mechanisms responsible for killing the beta cells but also to modify the beta cells to make them resistant to attack by these mechanisms. The multidisciplinary approach of the team will be directed to further understanding the genetic and environmental factors underlying type 1 diabetes and the immune mechanisms, particularly involving special white blood cells called T cells, that kill beta cells. A molecular target of the immune attack, the parent of insulin called proinsulin, will be used, paradoxically, as a tool to regulate the immune system and avert the attack. This will be achieved by giving proinsulin via the mucosa of the naso-respiratory tract or via the bone marrow-derived stem cells, initiallyin the mouse model as a test of feasibility for human application. In parallel with these approaches to prevention, specially constructed viruses will be used to transfer several new genes into beta cells to improve their resistance to immune attack, so that they can be transplanted into people with established diabetes without the need for potentially toxic drugs that suppress the immune system overall. The integrated research of the team is helping to provide a sound, rational base for the eventual prevention and cure of type 1 diabetes.Read moreRead less
I am the leading scientist studying a factor named BAFF and discovered its role in autoimmunity. BAFF inhibitors are effective in late stage clinical trials treating lupus patients. Our new work shows that BAFF has other fascinating roles, in particular the ability to control effects from some microbes capable of activating autoimmune and inflammatory reactions. This new work is leading us to the development of an entirely new generation of therapeutics treating autoimmunity and inflammation.