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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.
Identification Of Novel Strategies To Mediate Immunity Against Intracellular Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$325,084.00
Summary
The immune system consists of two arms - innate and adaptive. Current vaccine strategies rely mainly on adaptive features of the immune system to mediate immunity against pathogens. Many pathogens have evolved sophisticated strategies to manipulate the adaptive immune system to render it ineffective. This project will investigate microbial detection by the innate immune system, and aims to discover novel, more effective strategies to mediate immunity against intracellular pathogens.
Characterization Of Human-specific Anti-microbial Pathways
Funder
National Health and Medical Research Council
Funding Amount
$586,428.00
Summary
The immune system protects us against infectious disease by killing invading microbes or pathogens. Macrophages are white blood cells that are important for the recognition and destruction of pathogens. This project aims to investigate the role of certain genes, which are turned on in macrophages when they sense invading pathogens, in protecting us against infectious diseases such as tuberculosis and gastroenteritis.
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.
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