Discovery Early Career Researcher Award - Grant ID: DE200101300
Funder
Australian Research Council
Funding Amount
$423,711.00
Summary
Lipopolysaccharide-induced macrophage extracellular traps in host defence. The innate immune system is the first line of defence against invading microbes. Macrophages are key innate immune cells that deploy antimicrobial responses to clear infection and restore health. There are many critical unanswered questions on the molecular mechanisms that drive macrophage inflammatory and antimicrobial pathways. This project aims to elucidate a novel inflammatory mechanism that immobilises and kills inva ....Lipopolysaccharide-induced macrophage extracellular traps in host defence. The innate immune system is the first line of defence against invading microbes. Macrophages are key innate immune cells that deploy antimicrobial responses to clear infection and restore health. There are many critical unanswered questions on the molecular mechanisms that drive macrophage inflammatory and antimicrobial pathways. This project aims to elucidate a novel inflammatory mechanism that immobilises and kills invading bacteria via newly discovered structures made by dying macrophages called extracellular traps. Insight we gain by interrogating this immune cell signalling pathway, called the non-canonical inflammasome, will add valuable knowledge to our fundamental understanding of mammalian inflammation and anti-microbial responses
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The recirculation of myeloid dendritic cells. This project aims to understand dendritic cell recirculation. It will use virological tools to track dendritic cell migration, and identify key decision points. Expected outcomes include enhanced capacity in basic research and greater interdisciplinary collaboration between virology and immunology research groups. Significant benefits will include a new understanding of how G protein coupled receptor signalling and other tissue cues guide dendritic c ....The recirculation of myeloid dendritic cells. This project aims to understand dendritic cell recirculation. It will use virological tools to track dendritic cell migration, and identify key decision points. Expected outcomes include enhanced capacity in basic research and greater interdisciplinary collaboration between virology and immunology research groups. Significant benefits will include a new understanding of how G protein coupled receptor signalling and other tissue cues guide dendritic cell recirculation, and what consequences the recirculation has for immune cell function. This understanding will significantly advance our basic understanding of the immune system.Read moreRead less
Regulation of lung immune-epithelial networks sensing environmental change. This study aims to uncover how lung epithelial cells engage with immune cells and determine their cellular and molecular wiring to ensure homeostatic maintenance and essential repair processes of lung tissues. Maintenance of lung epithelial-immune networks is essential to maintain normal lung tissue structure and function, and to induce immune responses to protect against microbial challenges or inhaled potentially toxic ....Regulation of lung immune-epithelial networks sensing environmental change. This study aims to uncover how lung epithelial cells engage with immune cells and determine their cellular and molecular wiring to ensure homeostatic maintenance and essential repair processes of lung tissues. Maintenance of lung epithelial-immune networks is essential to maintain normal lung tissue structure and function, and to induce immune responses to protect against microbial challenges or inhaled potentially toxic substances. Understanding this molecular program of epithelial-immune cell-mediated sensing/repair will be essential to understand how tissue-repair processes can be driven in the lung, an organ critical for respiration and thus life.Read moreRead less
Mitochondria as sensors of environmental threats. This project aims to understand how energy-generating mitochondria control immune responses, both in immune cells called macrophages and in the nematode Caenorhabditis elegans (a free-living roundworm used as a model organism to study gene function and evolutionary biology). The project expects to advance knowledge of how a process called mitochondrial fission enables cells to respond to environmental threats. Expected outcomes include important ....Mitochondria as sensors of environmental threats. This project aims to understand how energy-generating mitochondria control immune responses, both in immune cells called macrophages and in the nematode Caenorhabditis elegans (a free-living roundworm used as a model organism to study gene function and evolutionary biology). The project expects to advance knowledge of how a process called mitochondrial fission enables cells to respond to environmental threats. Expected outcomes include important conceptual advances in cell biology and genetics, new international and national collaborations, and improved methods for cell biology research. Anticipated benefits include a knowledge base that can be indirectly applied in the long term in the development of new strategies to combat infections.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220100823
Funder
Australian Research Council
Funding Amount
$442,482.00
Summary
Elucidating ATPase function during NLRP3 inflammasome assembly. Humans and animals are constantly exposed to microbes, which inhabit their external environment as well as body surfaces such as the skin and gut. We are, however, able to co-exist with these microbes, because our immune system protects us from these everyday encounters. This proposal will reveal how an important immune protein called NLRP3 senses microbes and other physiological processes. When NLRP3 senses such factors and is acti ....Elucidating ATPase function during NLRP3 inflammasome assembly. Humans and animals are constantly exposed to microbes, which inhabit their external environment as well as body surfaces such as the skin and gut. We are, however, able to co-exist with these microbes, because our immune system protects us from these everyday encounters. This proposal will reveal how an important immune protein called NLRP3 senses microbes and other physiological processes. When NLRP3 senses such factors and is activated, it induces the release of messenger substances to alert other immune cells. This research will deliver fundamental knowledge of how animals normally co-exist with microbes.Read moreRead less
New Frontiers in Innate Immunity. This program aims to define how the immune system senses and responds to environmental cues. By combining interdisciplinary approaches with cutting-edge imaging and spatial biology technologies, this program expects to reveal how immune sensor proteins are regulated at the molecular, cellular and tissue level. Outcomes of this program include unparalleled insights into molecular mechanisms that underpin effective functioning of the immune system, training of fut ....New Frontiers in Innate Immunity. This program aims to define how the immune system senses and responds to environmental cues. By combining interdisciplinary approaches with cutting-edge imaging and spatial biology technologies, this program expects to reveal how immune sensor proteins are regulated at the molecular, cellular and tissue level. Outcomes of this program include unparalleled insights into molecular mechanisms that underpin effective functioning of the immune system, training of future scientists, and strengthening international collaborations across academia and industry. This will contribute to a high-quality workforce for research and innovation, and secure Australia’s position at the forefront of immunology research driven by cutting-edge technologies. Read moreRead less
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
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
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