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 NF-?B Transcription Factor RelA In Regulatory T Cell Homeostasis And Function
Funder
National Health and Medical Research Council
Funding Amount
$637,114.00
Summary
Treg cells constitute an immune regulatory cell population that is essential for the prevention of fatal autoimmunity; however, they also limit immunity against cancer. We have discovered that the factor RelA is of critical importance for Treg development and function. We now aim to illuminate the functions of RelA in detail. Understanding the molecules that impact on Treg cell biology is critical to harness their potential for clinical intervention such as treatment of autoimmunity and cancer.
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.
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.
Inflammatory diseases, such as autoimmune diseases, result from an overactive immune system. A new therapy that is currently under trial is the use of special blood cells, called Treg cells, whose function is to suppress unwanted immune responses. This application evaluates the efficacy and safety of such treatments.
Determining The Mechanisms Of Tolerance After Autologous Stem Cell Transplantation For Multiple Sclerosis – The Role Of CD39+ T Regulatory Cells
Funder
National Health and Medical Research Council
Funding Amount
$86,117.00
Summary
Autologous haematopoietic stem cell transplant offers relief for patients with aggressive forms of autoimmune diseases such as multiple sclerosis. Here, we aim to understand how this therapy relieves symptoms in multiple sclerosis patients by studying the biology of CD39+ T regulatory cells. Understanding these immune-suppressing cells can lead to the development of new transplant procedures without chemotherapy and ultimately improve transplant outcomes for autoimmune disease patients.