This project will investigate the factors that regulate the development and maintenance of a recently identified population of white blood cells called MAIT cells. MAIT cells are abundant in humans yet poorly understood. A better understanding of how these cells are regulated, and how they can be targeted in diseases, is necessary if we want to ultimately use these cells for immunotherapy.
MAIT cells are a recently discovered type of lymphocyte that plays a unique and important role in the immune system. However, these cells vary widely in number between healthy individuals, for reasons that are unclear. This project is designed to understand the factors that control the development of MAIT cells as a step toward regulating their numbers and activity.
Role Of The CD8-Heparan Sulfate Interaction In CD8+ T Cell Development And Function
Funder
National Health and Medical Research Council
Funding Amount
$649,135.00
Summary
The immune system can recognise a large array of foreign pathogens without reacting to self-components. For this to occur T cells, the main mediators of immunity, must be made to tolerate self-molecules as they develop in the thymus. We have identified a novel interaction between a molecule called CD8 on T cells and a complex carbohydrate called heparan-sulfate, which helps auto-reactive T cells to be eliminates in the thymus. The aim of this project is to further investigate this phenomenon.
The Mechanisms Of Epithelial Cell Survival That Govern Thymus Function
Funder
National Health and Medical Research Council
Funding Amount
$620,967.00
Summary
The thymus is an organ dedicated to the production of crucial immune cells, called T lymphocytes. Cancer treatments, such as radiation or chemotherapy, destroy thymic function and impair immune recovery in patients. We aim to uncover molecular processes that govern the life and death decisions of cells in the thymus. Our goal is to then use this information to develop treatments to protect this critical organ from damage and improve immune recovery following radiation or chemotherapy.
How Does NF-kB2 Regulate Thymic Selection To Prevent Organ-specific Autoimmune Disease?
Funder
National Health and Medical Research Council
Funding Amount
$787,600.00
Summary
Autoimmune diseases like type 1 diabetes and thyroiditis arise from defects that cause the immune system to confuse self and non-self. Normally, this distinction is programmed in the thymus. We recently identified the gene that causes a form of autoimmune disease. We also made an important discovery about how the thymus gland regulates self-non-self discrimination. We will build on these two discoveries to gain a precise understanding of how the immune system normally avoids autoimmune disease.
Stem Cell Based Strategies For Re-establishing T Cell Immunity In Aging And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$845,777.00
Summary
The thymus is the organ responsible for producing T cells, a key cell type in the body’s immune system. Certain cancer treatments damage the thymus, compromising the immune system and leaving patients susceptible to opportunistic infections. This proposal will develop clinically applicable strategies for generating functional human thymic mini-organs that could eventually help restore the immune system of people receiving treatment for cancer.
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
Asymmetric Cell Divison In T Cell Development: Consequences For Immunity And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$642,608.00
Summary
Human health depends upon the development of an immune system that can effectively control infection without damaging normal tissue. In this project, we assess a new paradigm by which immune cell development might be controlled, in which an immune cell precursor divides in such a way that its two daughters inherit different molecular constitutents that subsequently regulate the adoption of different cell fate. The likely consequences of this phenomonon on immunity and cancer will be explored.
The NF-kB Transcription Factors C-Rel And RelA Control Multiple Steps In Natural CD4 Regulatory T Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$566,592.00
Summary
An unfortunate consequence of immune function is that occasionally rogue immune cells are produced that attack the host and lead to the development of so-called autoimmune diseases such as arthritis. Normally a white blood cell called a regulatory T cell suppresses these self-reactive immune cells. We have identified factors that govern the generation of regulatory T cells. Understanding how these factors work should permit the development of new strategies to combat autoimmune diseases. ?