Sterile inflammation as a determinant of adaptive immunity. When we injure ourselves, the site of injury becomes inflamed, which may help healing or cause trouble. This project aims to understand how the normal response to injury is controlled and why the process may sometimes go wrong.
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
Regulated muscle-based thermogenesis for body temperature regulation. Mammals maintain a constant core body temperature by generating heat in resting muscles in response to changes in the environmental temperatures. This project aims to show how the skeletal muscles that are closer to the body core contribute the majority of heat, how the muscles of the limbs have their heat generation curtailed as necessary, and how this is coordinated by the body in response to ambient temperature. Project out ....Regulated muscle-based thermogenesis for body temperature regulation. Mammals maintain a constant core body temperature by generating heat in resting muscles in response to changes in the environmental temperatures. This project aims to show how the skeletal muscles that are closer to the body core contribute the majority of heat, how the muscles of the limbs have their heat generation curtailed as necessary, and how this is coordinated by the body in response to ambient temperature. Project outcomes include defining, for the first time, how heat generation in the muscles of the body is regulated. This should provide critical knowledge of mammalian evolution and ways to manipulate metabolism, which may provide ways to assist the production of meat by managing hypothermia and hyperthermia risk in agriculture.Read moreRead less
Cross-bridge cycling-dependent activation of force production in the absence of Ca2+ in fast- and slow-twitch skeletal muscle fibre types. The project will contribute new knowledge about how skeletal muscle works, which will be published in top international journals in biological sciences. This will increase the reputation of Australian science in muscle research and will have the potential to benefit Australian people and Australian athletes. The project will also provide several Australian re ....Cross-bridge cycling-dependent activation of force production in the absence of Ca2+ in fast- and slow-twitch skeletal muscle fibre types. The project will contribute new knowledge about how skeletal muscle works, which will be published in top international journals in biological sciences. This will increase the reputation of Australian science in muscle research and will have the potential to benefit Australian people and Australian athletes. The project will also provide several Australian research students the opportunity to develop sophisticated laboratory and reasoning skills.Read moreRead less
Age-related mechanisms of amino acid signalling in skeletal muscle. This project aims to increase our understanding of the role of glycine receptor-mediated signalling and its metabolism in the amino acid sensing capacity of mTORC1, a key enzyme regulating muscle protein synthesis. Ageing is associated with a progressive decline in skeletal muscle mass, weakness, and impaired regeneration after injury. Impaired anabolic signalling after food intake has been proposed as a key contributor, yet the ....Age-related mechanisms of amino acid signalling in skeletal muscle. This project aims to increase our understanding of the role of glycine receptor-mediated signalling and its metabolism in the amino acid sensing capacity of mTORC1, a key enzyme regulating muscle protein synthesis. Ageing is associated with a progressive decline in skeletal muscle mass, weakness, and impaired regeneration after injury. Impaired anabolic signalling after food intake has been proposed as a key contributor, yet the metabolic pathways responsible for nutrient sensing and regulation of protein synthesis remain unresolved. The project will assess defective amino acid sensing and protein synthesis in old mammals, identifying the role of glycine signalling in these processes. The project expects to underpin development of muscle-specific modulators of muscle homeostasis with broad relevance to Australia’s ageing population.Read moreRead less
How tissues generate the peptide hormone angiotensin II. This project aims to investigate how local tissue renin-angiotensin systems operate. A blood-borne renin–angiotensin system (RAS) produces a peptide (AngII) to control blood pressure, and fluid/salt balance. Many tissues, such as the brain and heart, also possess an independent, tissue RAS, but how these function is not well understood. The project will use a model whereby infiltrating macrophages (following damage to the heart) drive the ....How tissues generate the peptide hormone angiotensin II. This project aims to investigate how local tissue renin-angiotensin systems operate. A blood-borne renin–angiotensin system (RAS) produces a peptide (AngII) to control blood pressure, and fluid/salt balance. Many tissues, such as the brain and heart, also possess an independent, tissue RAS, but how these function is not well understood. The project will use a model whereby infiltrating macrophages (following damage to the heart) drive the activation of this system to trigger the local generation of AngII. This project addresses the question of where exactly in the heart the RAS components are turned on, how they interact to generate AngII and whether the activation of the local RAS is beneficial or not to cardiac function. The findings should provide critical insights into an important hormonal system.Read moreRead less
Regulation of local lymphocyte trafficking and its role during infection. The study of early immune responses will contribute to the development of better vaccination strategies. In particular it will contribute by helping to understand the essential differences between reactogenicity and immunogenicity and how this relates to adjuvants. Using this understanding it will be possible to develop novel adjuvants that induce appropriate immunity with minimal side effects.
Novel ways of regulating epithelial transport. This project is intended to discover novel intracellular mechanisms that regulate the rate of ion transport by the lung, the gut and the kidney. It will not only provide new insights into how the body controls a process that is critical to animal life, but also provide new targets for the development of pharmaceuticals.
Structural Determinants of an Intracellular Calcium Store. Understanding the molecular interactions between key proteins in calcium signalling in muscle and the heart will allow calcium signalling to be used as a platform for a variety of purposes. These include reducing the debilitating effects of changes in calcium signalling and muscle performance in aging and in genetically- or drug-induced disorders. The project will have benefits for Australian biotechnology since it will facilitate the de ....Structural Determinants of an Intracellular Calcium Store. Understanding the molecular interactions between key proteins in calcium signalling in muscle and the heart will allow calcium signalling to be used as a platform for a variety of purposes. These include reducing the debilitating effects of changes in calcium signalling and muscle performance in aging and in genetically- or drug-induced disorders. The project will have benefits for Australian biotechnology since it will facilitate the design of novel compounds for treating muscle disorders in animals and humans, for improving meat quality and for use as insecticides. The project will facilitate graduate and undergraduate training in basic science with exposure to biotechnology, through our commercial partner Biotron.Read moreRead less
The sulfate anion transporter gene, Sat1: physiology, regulation and developmental expression. Sulfate is an essential nutrient for cell growth and survival. The kidneys and liver help regulate sulfate levels in the body, by yet unknown mechanisms. Recently, we cloned a gene, Sat1, expressed in mouse liver and kidneys, which may be responsible for body sulfate maintenance. In this study, we will determine the physiological importance of Sat1 in cell growth/survival and in controlling body sulfa ....The sulfate anion transporter gene, Sat1: physiology, regulation and developmental expression. Sulfate is an essential nutrient for cell growth and survival. The kidneys and liver help regulate sulfate levels in the body, by yet unknown mechanisms. Recently, we cloned a gene, Sat1, expressed in mouse liver and kidneys, which may be responsible for body sulfate maintenance. In this study, we will determine the physiological importance of Sat1 in cell growth/survival and in controlling body sulfate levels. We will generate and characterise a Sat1 lacking mouse, study its expression during development and its effects on other genes. We will elucidate how body sulfate levels are maintained and its importance in cell growth/development.Read moreRead less