Understanding The Role Of Innate Immune Cells In Regulating Gut-associated Lymphoid Tissues At Steady-state And In Disease
Funder
National Health and Medical Research Council
Funding Amount
$365,126.00
Summary
The intestine is the largest surface area forming a protective barrier between the external environment and the body. It represents the first line of defence against invading pathogens. The immune system of the intestine is critical to protect this tissue -any breakdown leads to profound and progressive inflammatory disease of the gut such as chronic inflammatory bowel disease. Our work will determine the critical the mechanisms that protect the gut opening the door to targeted intestinal immuno ....The intestine is the largest surface area forming a protective barrier between the external environment and the body. It represents the first line of defence against invading pathogens. The immune system of the intestine is critical to protect this tissue -any breakdown leads to profound and progressive inflammatory disease of the gut such as chronic inflammatory bowel disease. Our work will determine the critical the mechanisms that protect the gut opening the door to targeted intestinal immunotherapeutics.Read moreRead less
Molecular And Functional Charcterization Of A Novel Population Of Foxp3+ Regulatory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$394,274.00
Summary
Regulatory T cells (Tregs) are essential for the prevention of autoimmunity and death. We have identified a new population of effector or ïactiveÍ Tregs, and identified some of the proteins that are required for these cells to function. We now aim to examine the development of these cells in detail, illuminate their precise function, their distribution and mode of action. This has potentially huge implications in treatment and diagnosis of autoimmunity, cancer or transplantation.
Dissecting In Vivo Cellular Responses To Interferons In Pathogen-infected Hosts
Funder
National Health and Medical Research Council
Funding Amount
$479,694.00
Summary
Tuberculosis (TB) is caused by virulent bacterium Mycobacterium tuberculosis and is a leading cause of death worldwide. Mechanisms underlying host resistance to the pathogen are poorly understood. Using a novel reporter mouse, the function of interferons in Mtb infection will be defined in vivo by tracking the cytokine-responsive cells. This will increase our understanding of the effects of these important cytokines in vivo, and could provide new candidate biomarkers for TB diagnosis.
Maintenance Of Regulatory T Cells During Inflammation And Tumor Development By IL-33
Funder
National Health and Medical Research Council
Funding Amount
$676,979.00
Summary
Regulatory T cells (Tregs) are required for preventing inflammation in tissues such as lung, fat and skin. We found recently, that the signalling molecule IL-33 is required for tissue Tregs and up-regulated during inflammation and tumor development. We therefore aim to determine the role of IL-33 in maintenance and function of Tregs and to identify molecular targets of IL-33 that may allow therapeutic targeting of Tregs in patients with inflammatory conditions or cancer.
Regulation Of Metabolic Dysfunction And Exhaustion Of Virus-specific T Cells During Chronic Infection
Funder
National Health and Medical Research Council
Funding Amount
$749,152.00
Summary
T cells control infections and cancer cells. During chronic infection or tumor development, however, loss of function of T cells prevents efficient clearing of pathogens or cancer cells, a phenomenon termed T cell ‘exhaustion’. We have found that the regulator protein IRF4 controls cellular nutrient usage, growth and function of T cells and that very amounts of IRF4 occur in T cells during chronic infection. We propose to examine the precise role of IRF4 in chronically stimulated T cells.
During an immune response a white blood cell, the T lymphocyte, receives a series of signals that manipulate cell survival and proliferation. The team at WEHI will identify the effects of key signals on the molecular control of T cell survival. The results will be used to test a new method for inducing tolerance and dampening unwanted immune responses, such as during tissue graft rejection and autoimmunity.
Our bodies rely on the production of potent, or ‘high affinity’, antibodies to fight infection. We have found that antibody responses are unexpectedly boosted following the depletion of a specific subset of immune cells. This is especially true for B cells that are poor antibody producers. Our findings are likely to be relevant to (1) the design of vaccines to infectious agents that have important CTL and antibody components (e.g. HIV), (2) for the improved production of antibody for therapeutic ....Our bodies rely on the production of potent, or ‘high affinity’, antibodies to fight infection. We have found that antibody responses are unexpectedly boosted following the depletion of a specific subset of immune cells. This is especially true for B cells that are poor antibody producers. Our findings are likely to be relevant to (1) the design of vaccines to infectious agents that have important CTL and antibody components (e.g. HIV), (2) for the improved production of antibody for therapeutic use (e.g. cancer).Read moreRead less
Identification Of E-protein Complexes Controlling Natural Killer Cell Fate And Tumour Immunity
Funder
National Health and Medical Research Council
Funding Amount
$683,742.00
Summary
Diverse immune cell types are essential for effective broad-spectrum immunity. Master regulators control this diversity and have a well-characterized role in the development of antigen-specific immunity. In contrast, we lack mechanistic understanding of how master regulators control antigen-unspecific, innate immunity. Understanding the mechanism behind this will explain how diverse white blood cells can develop and reveal strategies to skew their development to improve immunity in humans.
Roles Of ID2 In Regulating Critical Innate And Adaptive Arms Of The Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$597,418.00
Summary
The immune system protects us from a wide range of pathogens and foreign invaders. Natural killer (NK) cells and T cells are an critical component of the immune system due to their ability to detect and kill virally infected and malignant cells. Our work will endeavor to understand the molecular steps essential for these cells to develop and become armed to ensure immune protection.
Multiple Paths Of TFH Differentiation And Their Impact On B Cell Protection Against Infection
Funder
National Health and Medical Research Council
Funding Amount
$923,466.00
Summary
Collaboration between T and B cells is crucial for immune protection and underpins current vaccine strategies. We have revealed an unappreciated flexibility that exists in T cell responses which varies the instructions they give B cells. It is likely this tailors immune responses to ensure protection to countless infectious diseases. This project uses cutting-edge technologies to understand this flexibility and has important implications for vaccine design and treatment of infectious disease.