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