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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.
Nuclear alarmins escalate tissue immune responses. Humans and other animals are constantly exposed to potential threats, including microbes on and near the body. Animals can live with such dangers because these everyday encounters are made harmless by the immune system. It is unclear how cells distinguish low-danger threats from high-danger threats. This proposal seeks to reveal how immune cells identify increasing levels of threat and appropriately escalate their responses. Expected outcomes in ....Nuclear alarmins escalate tissue immune responses. Humans and other animals are constantly exposed to potential threats, including microbes on and near the body. Animals can live with such dangers because these everyday encounters are made harmless by the immune system. It is unclear how cells distinguish low-danger threats from high-danger threats. This proposal seeks to reveal how immune cells identify increasing levels of threat and appropriately escalate their responses. Expected outcomes include new insights into how immune cells and tissues respond according to the posing threat. Project benefits include understanding how to manipulate danger responses for future basic research and commercial applications, and fundamental understanding of how animals flourish in a dangerous world.Read moreRead less
A novel mechanism of host defence via macrophage extracellular traps. Animal health relies upon innate immune cells to rapidly detect invading microbes and induce inflammatory and antimicrobial responses to clear infection. Mechanisms of inflammation and immune defence are only partly understood. This project aims to elucidate a novel innate immune pathway (the inflammasome) that drives inflammatory cell death and antimicrobial defence. Using innovative multidisciplinary methods, this project wi ....A novel mechanism of host defence via macrophage extracellular traps. Animal health relies upon innate immune cells to rapidly detect invading microbes and induce inflammatory and antimicrobial responses to clear infection. Mechanisms of inflammation and immune defence are only partly understood. This project aims to elucidate a novel innate immune pathway (the inflammasome) that drives inflammatory cell death and antimicrobial defence. Using innovative multidisciplinary methods, this project will yield exciting new knowledge of mechanisms of inflammation and anti-microbial responses, and new paradigms for inflammasome action. Expected outcomes and benefits include high-impact publications, international collaboration, world-class training for young scientists, and new knowledge for future commercialisation.Read moreRead less
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
Molecular basis of nucleotide signalling by TIR domain containing proteins. Nicotinamide adenine dinucleotide (NAD+) dependent signalling pathways play important roles in neurodegenerative diseases and bacterial defence systems, and are therefore potential targets for the development of new therapeutics and biotechnology tools. This project aims to increase our understanding of the biology of a novel class of enzymes involved in NAD+ signalling across the domains of life. The project is expected ....Molecular basis of nucleotide signalling by TIR domain containing proteins. Nicotinamide adenine dinucleotide (NAD+) dependent signalling pathways play important roles in neurodegenerative diseases and bacterial defence systems, and are therefore potential targets for the development of new therapeutics and biotechnology tools. This project aims to increase our understanding of the biology of a novel class of enzymes involved in NAD+ signalling across the domains of life. The project is expected to unravel general principles of nucleotide-based signalling, and the expected outcomes will include new molecular mechanisms relevant to cell-death and pathogen defence in mammalian and bacterial systems, which should provide significant benefit for a range of applications in human biology and biotechnology.Read moreRead less
How filopodia connect macrophages to the outside world. Fundamental to life is the ability of cells to sense their surroundings and respond accordingly. This project aims to generate a biological understanding of how certain immune cells carry out such processes, thus enabling them to combat infections.
Australian Laureate Fellowships - Grant ID: FL180100109
Funder
Australian Research Council
Funding Amount
$2,762,247.00
Summary
Unifying mechanisms of innate immunity signaling in animals and plants. This project aims to improve our understanding of innate immunity, the first line of defense against pathogens in diverse organisms. Innate immune pathways are key to a range of pathological states in animals, and provide plants with resistance to the diseases that account for 15% of crop losses. This project will generate knowledge, through characterising mechanisms of cell signalling for mammalian and plant innate immunity ....Unifying mechanisms of innate immunity signaling in animals and plants. This project aims to improve our understanding of innate immunity, the first line of defense against pathogens in diverse organisms. Innate immune pathways are key to a range of pathological states in animals, and provide plants with resistance to the diseases that account for 15% of crop losses. This project will generate knowledge, through characterising mechanisms of cell signalling for mammalian and plant innate immunity. The outcomes will include a unified signalling model, and form the foundation for a range of applications in human biology and agriculture, such as the development of durable and effective resistance in crops.Read moreRead less