Novel Posttranscriptional Pathways The Control Tfh Cell Numbers
Funder
National Health and Medical Research Council
Funding Amount
$647,539.00
Summary
T follicular helper (Tfh) cells are essential for effective antibody responses against infection. Limiting Tfh cells is crucial for selecting the "fittest" B cells and the success of vaccines. Tfh cell accumulation causes autoimmuity and is associated with inadequate B cell responses in HIV infection. We have recently discovered two novel pathways that control Tfh cells. We speculate they regulate different RNAs that influence Tfh homeostasis and aim to elucidate their mechanism of action.
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.
Positive And Negative Selection In The Germinal Centre Reaction
Funder
National Health and Medical Research Council
Funding Amount
$1,289,965.00
Summary
We will investigate the processes that control the production of antibodies by the immune system. In particular, we will determine how the immune system is normally prevented from producing autoantibodies that target the body's own cells and how this fails in the case of autoimmune diseases such as lupus. Targeted studies of a new type of "rogue" white blood cell we have identified will also provide important clues on how autoantibody-producing cells escape and cause autoimmune disease.
How BANK1 Pathway Defects In B Cells Cause Human Lupus
Funder
National Health and Medical Research Council
Funding Amount
$1,316,839.00
Summary
Autoimmune diseases affect 1 in 20 Australians and are incurable. To find effective therapies, we need to understand the genes that cause disease in humans. We have sequenced the entire genome of patients with an autoimmune disease and found several patients carrry two mutations in genes important for activation of B cells and shown these mutations cause disease. We plan to understand how these genes prevent autoimmunity, and to identify the best treatment for patients with these mutations.
Antigen Presentation During HLA B27 Associated Auotimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$715,365.00
Summary
Ankylosing spondylitis is a debilitating arthritic disease, susceptibility to which is conferred by genes of the immune system, particularly HLA-B27, and following gastrointestinal infection. Using mass spectrometry we will identify bacterial peptides bound to HLA-B27 on infected cells that may trigger an autoimmune response. Defining the self peptides that remain the targets of autoimmunity will unravel the molecular and cellular mechanisms if disease and identify peptides for immunotherapy.
Pathogenesis Of A New Mouse Model Of Ankylosing Spondylitis
Funder
National Health and Medical Research Council
Funding Amount
$682,820.00
Summary
Ankylosing spondylitis and Crohn's disease are autoimmune inflammatory diseases which cause long-term pain and deformity of joints, spine and bowel. Using a new mouse model of both diseases, we will study cells and processes involved in the initiation of disease, in order to discover new targets for prevention and treatment. The work will have importance for design of new therapies for human inflammatory spine and bowel diseases.
The Role Of NOD Proteins In T Cell Development And Function.
Funder
National Health and Medical Research Council
Funding Amount
$349,590.00
Summary
The long-term goal of this project is to understand the role of NOD proteins in the T cell branch of the immune system. Distorted T cell responses can lead to over-activation and autoimmunity, or host susceptibility to microbial infection. This project aims to provide a deeper understanding of NOD proteins in chronic inflammatory diseases like Crohn’s disease, where altered NOD signaling may generate intrinsic T cell defects, in addition to altered microbial sensing and host protection by the in ....The long-term goal of this project is to understand the role of NOD proteins in the T cell branch of the immune system. Distorted T cell responses can lead to over-activation and autoimmunity, or host susceptibility to microbial infection. This project aims to provide a deeper understanding of NOD proteins in chronic inflammatory diseases like Crohn’s disease, where altered NOD signaling may generate intrinsic T cell defects, in addition to altered microbial sensing and host protection by the innate immune system.Read moreRead less