The Influence Of NF-KB In The Development Of Autoimmunity And Cancer In Fas/FasL Mutant Mice
Funder
National Health and Medical Research Council
Funding Amount
$596,925.00
Summary
Apoptotic cell death is an essential process in the human body, it removes useless and dangerous cells, preventing autoimmune disease and cancer. Apoptosis is activated when the surface receptor Fas is stimulated by its ligand, FasL, but defective signalling causes disease associated with deregulated NF-?B activation. We will investigate how faulty FasL-induced apoptosis cooperates with deregulated NF-kB activation or defective Aire (immunological tolerance orchestrator) results in autoimmunity.
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
Applying Quantitative Immunology To The Analysis Of Complex Genetic Diseases
Funder
National Health and Medical Research Council
Funding Amount
$864,596.00
Summary
The immune response of each individual varies. For some, the response invoked by foreign challenge is weak, leading to a lifetime of difficulty with infection. For others, the response is stronger, yielding excellent immunity, but opening the potential for overactive responses to self-material and autoimmune disease. We have a new theory for how the health of our immune system can be measured and we aim to apply it to understand the genesis of the many different forms of human immune diseases.
Defining The Molecular Regulators Of Apoptotic Cell Disassembly And Their Role In Cell Clearance And Lupus-like Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$773,848.00
Summary
In humans, billions of cells will die daily as part of normal turnover in various organs. It is vital that dying cells are rapidly removed as their accumulation has been linked to autoimmunity and inflammation. To aid efficient removal of dead cells, dying cells can disassemble into smaller fragments for neighbouring cells to engulf. We aim to understand the machinery that controls how dying cells can disassemble into smaller pieces and their function in cell clearance and autoimmunity.
The Mechanism For Combined Immunodeficiency And Autoimmunity Due To STK4-deficiency And Its Broader Application To Human PIDs
Funder
National Health and Medical Research Council
Funding Amount
$648,371.00
Summary
Why do some patients develop autoimmune diseases such as lupus where the immune system makes antibodies that attack its own body? To answer this, we plan to study a disease where a gene responsible for making antibodies is defective. Patients with mutations in the STK4 gene are unable to regulate the selection processes by which only the right cell is chosen to make antibodies. Understanding how STK4 works may help us unlock the mystery of what causes lupus.
Early Environmental Determinants Of Pancreatic Islet Autoimmunity: A Pregnancy To Early Life Cohort Study In Children At Risk Of Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$1,124,069.00
Summary
The doubling in incidence of type 1 diabetes in children over the last 20 years may be explained by our modern environment, including excessive weight gain in pregnancy and early life, inadequate dietary omega- 3 fatty acids or vitamin D, or viral infections. We therefore aim to study children with a family member with type 1 diabetes from the pregnancy and through early childhood to determine the effects of the environment on their risk of developing type 1 diabetes .This will lead to strategie ....The doubling in incidence of type 1 diabetes in children over the last 20 years may be explained by our modern environment, including excessive weight gain in pregnancy and early life, inadequate dietary omega- 3 fatty acids or vitamin D, or viral infections. We therefore aim to study children with a family member with type 1 diabetes from the pregnancy and through early childhood to determine the effects of the environment on their risk of developing type 1 diabetes .This will lead to strategies to prevent type 1 diabetes.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.
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.
TLR9 AGGRAVATES GLOMERULONEPHRITIS AND KIDNEY INJURY IN RENAL VASCULITIS
Funder
National Health and Medical Research Council
Funding Amount
$349,336.00
Summary
Renal failure is a significant cause of morbidity and mortality in Australia. Anti-neutrophil cytoplasmic antibody (ANCA) vasculitis associated glomerulonephritis (GN) is a significant cause of renal failure. The molecular mechanisms underlying ANCA vasculitis are poorly understood, while treatments are associated with considerable morbidity and mortality. This grant aims to explore key molecular events involved in the disease pathogenesis to facilitate the use of safer more targeted therapies.