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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 axis of cooperation between innate and adaptive immunity. The project aims to understand how two molecular components of the immune system, Complement and MHC, cooperate to protect the host. Further, these two molecules mediate trogocytosis, a little-studied form of intercellular communication, between two major immune cell types: dendritic cells and B cells. The project will be multidisciplinary, applying high-end microscopy, biochemistry, cell biology and immunology techniques. Person ....A novel axis of cooperation between innate and adaptive immunity. The project aims to understand how two molecular components of the immune system, Complement and MHC, cooperate to protect the host. Further, these two molecules mediate trogocytosis, a little-studied form of intercellular communication, between two major immune cell types: dendritic cells and B cells. The project will be multidisciplinary, applying high-end microscopy, biochemistry, cell biology and immunology techniques. Personnel will be trained in cutting-edge techniques. The project will expand knowledge on basic immunology and cell-cell cooperation. It will generate intellectual property for the biotechnology sector to develop new commercial products that might improve the health of humans and also animals of economic importance.Read moreRead less
Programmed cell death signalling in innate immunity. This proposal aims to address the under-explored potential for programmed cell death to promote innate immune cell signalling, which is a critical and fundamental biological process. It aims to generate new knowledge in the areas of cell death and innate signalling using innovative interdisciplinary approaches and discover new molecules that impact innate inflammatory responses. The expected outcomes of this project are to enhance our basic un ....Programmed cell death signalling in innate immunity. This proposal aims to address the under-explored potential for programmed cell death to promote innate immune cell signalling, which is a critical and fundamental biological process. It aims to generate new knowledge in the areas of cell death and innate signalling using innovative interdisciplinary approaches and discover new molecules that impact innate inflammatory responses. The expected outcomes of this project are to enhance our basic understanding of cell death, and build interdisciplinary collaborations. This work should provide significant benefit to the economy and health of Australians, as it is expected to identify molecules that will be of interest to the pharmaceutical and biotechnology industries.Read moreRead less
Elucidating the roles of steroid receptors in mitochondria. This project aims to elucidate the roles of newly discovered steroid receptors in the functions of mitochondria. The project will characterise their impact on cellular respiration, oxidative stress, and the induction of inflammation. By defining these processes in the healthy state and in response to common environmental challenges of infection and smoke exposure, the project will characterise the fundamental biology of entirely new pro ....Elucidating the roles of steroid receptors in mitochondria. This project aims to elucidate the roles of newly discovered steroid receptors in the functions of mitochondria. The project will characterise their impact on cellular respiration, oxidative stress, and the induction of inflammation. By defining these processes in the healthy state and in response to common environmental challenges of infection and smoke exposure, the project will characterise the fundamental biology of entirely new processes of how normal body hormones and administered steroids may function. This may eventually lead to new and more effective ways to control inflammation that will have significant benefits to mammalian health and improve health care and agriculture outcomes.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220101491
Funder
Australian Research Council
Funding Amount
$443,312.00
Summary
A molecular investigation into metabolite-mediated T cell immunity. This project aims to undertake discovery research to investigate the roles of metabolites in T cell immunity. This project expects to generate new knowledge in the areas of cellular biology and immunology by using cutting-edge molecular and immunological approaches. This will provide fundamental insights into the mechanisms that govern microbial metabolite-based T cell immunity, which may advise future research into vaccines or ....A molecular investigation into metabolite-mediated T cell immunity. This project aims to undertake discovery research to investigate the roles of metabolites in T cell immunity. This project expects to generate new knowledge in the areas of cellular biology and immunology by using cutting-edge molecular and immunological approaches. This will provide fundamental insights into the mechanisms that govern microbial metabolite-based T cell immunity, which may advise future research into vaccines or therapeutics. In addition to knowledge gains, expected outcomes of this project include the development of innovative methodology and building international collaborations to enhance national research capabilities. This will place Australia at the forefront of conceptually innovative discovery in the life sciences.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
Augmenting the activity of glyoxalase-1 to increase dicarbonyl clearance . Reactive intermediates generated during our metabolism contribute to ageing. Glyoxalase-1 is a key defence enzyme against these toxic intermediates and therefore ageing itself. This project aims to investigate novel pathways how the expression and activity of glyoxalase-1 are regulated. This interdisciplinary project expects to generate new understanding by combining relevant cell and animal models, protein chemistry, epi ....Augmenting the activity of glyoxalase-1 to increase dicarbonyl clearance . Reactive intermediates generated during our metabolism contribute to ageing. Glyoxalase-1 is a key defence enzyme against these toxic intermediates and therefore ageing itself. This project aims to investigate novel pathways how the expression and activity of glyoxalase-1 are regulated. This interdisciplinary project expects to generate new understanding by combining relevant cell and animal models, protein chemistry, epigenetics and structural biology. It is expected that this work will improve understanding of this fundamental biological defence. This will allow us to identify the potential means to enhance the capacity of glyoxalase-1 to the future benefit of biological ageing.Read moreRead less
Signaling in the crypt: a novel metabolic pathway in intestinal stem cells. The gut is the most rapidly renewing tissue in the body, driven by a highly active stem cell niche. Bile acids are emerging as critical regulators of this stem cell niche and disruption of bile acid homeostasis has profoundly adverse effects on intestinal renewal and hence gut health. We are addressing a critical gap in our understanding of how bile acids are controlled within stem cell niche. The aim of the project is ....Signaling in the crypt: a novel metabolic pathway in intestinal stem cells. The gut is the most rapidly renewing tissue in the body, driven by a highly active stem cell niche. Bile acids are emerging as critical regulators of this stem cell niche and disruption of bile acid homeostasis has profoundly adverse effects on intestinal renewal and hence gut health. We are addressing a critical gap in our understanding of how bile acids are controlled within stem cell niche. The aim of the project is to define the critical role of a novel enzyme called UGT8 in controlling intestinal stem cell response to bile acids; this is achieved by modulating UGT8 activity in intestinal stem cell models and determining the effects on stem cell function and the key signalling pathways that control intestinal homeostasis and renewal.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220100259
Funder
Australian Research Council
Funding Amount
$467,964.00
Summary
Interrogating the adaptive potential of skeletal muscle. Disruptions to muscle oxidative capacity and growth signalling underpin atrophy and dysfunction with ageing, which impacts on an individual’s quality of life. These biological processes are thought to be mutually exclusive and compete during muscle adaptation. This project aims to define how these processes regulate the extent of muscle adaptation, and how modifying these attributes influence functional capacity in the context of ageing. T ....Interrogating the adaptive potential of skeletal muscle. Disruptions to muscle oxidative capacity and growth signalling underpin atrophy and dysfunction with ageing, which impacts on an individual’s quality of life. These biological processes are thought to be mutually exclusive and compete during muscle adaptation. This project aims to define how these processes regulate the extent of muscle adaptation, and how modifying these attributes influence functional capacity in the context of ageing. This project will provide fundamental new knowledge in understanding how modifying muscle attributes influence successful ageing. This knowledge will improve resilience, productivity, and wellbeing of all Australians, with implications for reducing societal and economic burden.Read moreRead less