The Role Of Perivascular Macrophages In The Regulation Of CNS Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$602,609.00
Summary
Inflammation of the central nervous system can have deleterious consequences. How the inflammatory cascade operates within the CNS is poorly understood. We have recently discovered a novel subset of immune cells, the perivascular macrophage, which regulates the recruitment of inflammatory cells. Aim of this proposal is to dissect the role of these cells during brain infections and autoimmune inflammation.
The Regulatory Role Of Clec12A In Antigen Presentation And Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,381,077.00
Summary
The immune system maintains a balance between initiating immune responses to infections and suppressing immune responses in health. We have identified, on the surface of specialised immune cells, a protein that is critical for regulating immune responses and dampening down inflammation. This proposal aims to determine how this protein functions in health and under inflammatory conditions, and to develop approaches based on its molecular interactions to reduce inflammatory disease.
SNARE-mediated perforin and cytokine release in natural killer cells. Cytotoxic cells release toxic granules and cytokine messengers to kill pathogen infected and cancerous cells and to mount immune responses. This project will investigate different SNARE molecules that regulate the secretion of perforin from granules and cytokines from other carriers, assisting in the understanding of complex but essential cellular pathways.
Structural And Functional Investigation Of Killer-Cell Immunoglobulin-like Receptors
Funder
National Health and Medical Research Council
Funding Amount
$546,966.00
Summary
Natural Killer (NK) cells are an important component of the immune response to cancer and infection. This project will define the molecular targets that are recognised by NK cells. This knowledge can then be used as a guide in the selection of bone marrow donors in the treatment of leukaemias as well as understanding how we fight infections.
Understanding Natural Killer Cell Development And Target Recognition
Funder
National Health and Medical Research Council
Funding Amount
$408,388.00
Summary
Immune detection and eradication or control of cancer and cancer immunotherapies are based in part on the idea that tumour-specific white blood cells can protect the body from tumour development, growth and metastases. While strong evidence supports this, the means by which these white cells first recognize the cancerous tissue is largely unknown. We will study a new family of white blood cell receptors that may be important in this recognition, either naturally or following therapy.
Structural And Functional Studies Of The Human IL-3 Receptor
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
This proposal will study a protein hormone that is implicated in blood cell cancers and inflammatory diseases and for which current treatments are inadequate. We will determine how the hormone receptor becomes activated, identify and characterise new agents that block this activation. This information will help in the development of new and highly specific drugs for use in certain cancers in inflammatory diseases.
Cholesterol and Hydroxycholesterol Shaping Phagocytosis. Reports now show that membrane cholesterol and 25-hydroxycholesterol (25HC) are required for immune cells to ingest and kill pathogens by phagocytosis. This project will measure phagocytosis in macrophages with genetically or pharmacologically varied cholesterol and 25HC, to compare and quantify the ingestion of different bacteria, fungi and particles. This project will also address the link between cholesterol synthesis, its storage in li ....Cholesterol and Hydroxycholesterol Shaping Phagocytosis. Reports now show that membrane cholesterol and 25-hydroxycholesterol (25HC) are required for immune cells to ingest and kill pathogens by phagocytosis. This project will measure phagocytosis in macrophages with genetically or pharmacologically varied cholesterol and 25HC, to compare and quantify the ingestion of different bacteria, fungi and particles. This project will also address the link between cholesterol synthesis, its storage in lipid bodies and its availability for phagocytosis, based on preliminary data showing such defects in the staggerer mouse model. Notably, cholesterol dysregulation is now a prevalent condition in society and our results will reveal at a fundamental, molecular level how this might compromise immune defenses.Read moreRead less
Structural And Functional Characterisation Of The Killer Cell Immunoglobulin-like Receptor (KIR) Family Of Natural Killer Cell Receptors
Funder
National Health and Medical Research Council
Funding Amount
$348,070.00
Summary
Natural Killer (NK) cells are an important component of the immune response to cancer and infection. This project will define the molecular targets that are recognised by NK cells. This knowledge can then be used to guide in the selection of bone marrow donors in the treatment of leukemias as well as understanding how we fight off infections.
The Interferon System In Innate Immune Responses To Disease
Funder
National Health and Medical Research Council
Funding Amount
$836,818.00
Summary
My research investigates special proteins called cytokines in the body’s first-line defence against infection, inflammation and cancer. I will characterise how cells respond, the signals that mediate effects, using sophisticated genetic and new computational techniques to manage and analyse data. One focus is a new cytokine we discovered that protects against infections of the reproductive tract –a global health and socio-economic problem affecting 1 billion people.