Regulating calcium handling in skeletal muscle - implications for muscle contraction, injury and repair, ageing and development. Understanding the mechanisms regulating calcium in skeletal muscle has important relevance for studying muscle growth and development, injury and repair, and for identifying therapeutic targets and potential therapies for ageing-related disorders, reconstructive surgery, sporting and workplace injuries, and muscle diseases. Combining cell physiology, fluorescence micro ....Regulating calcium handling in skeletal muscle - implications for muscle contraction, injury and repair, ageing and development. Understanding the mechanisms regulating calcium in skeletal muscle has important relevance for studying muscle growth and development, injury and repair, and for identifying therapeutic targets and potential therapies for ageing-related disorders, reconstructive surgery, sporting and workplace injuries, and muscle diseases. Combining cell physiology, fluorescence microscopy and digital imaging technologies for studying multicellular tissues such as skeletal muscle will enhance the international competitiveness of Australian biological research. The research will optimise development of gene delivery systems that may find eventual application for muscle wasting disorders and conditions where muscle weakness compromises quality of life.Read moreRead less
Fluid Dynamics of Circulation: Focus on the Kidney. In Australia, about 30% of adults have hypertension, a major risk factor for heart disease, accounting for about 40% of all deaths. Problems in renal circulation are likely factors leading to hypertension. A detailed understanding of the renal circulation, of whose hydraulic characteristics we have limited knowledge, is required before we can cure or prevent hypertension. We will determine how the size, structure and geometry of the blood vesse ....Fluid Dynamics of Circulation: Focus on the Kidney. In Australia, about 30% of adults have hypertension, a major risk factor for heart disease, accounting for about 40% of all deaths. Problems in renal circulation are likely factors leading to hypertension. A detailed understanding of the renal circulation, of whose hydraulic characteristics we have limited knowledge, is required before we can cure or prevent hypertension. We will determine how the size, structure and geometry of the blood vessels influence the function of the kidney. This will lead to predictive models to aid the design and interpretation of physiological studies and the combat of hypertension. It will also help in the ongoing development of bioartificial kidneys to replace present dialysis systems. Read moreRead less
Plasticity in placental vasculature and the evolution of viviparity in lizards. This cross-disciplinary research will provide thorough understanding of the reproductive physiology of animals with different forms of reproduction, information critical for conservation and management of Australia's biodiversity. Australia's unique reptiles provide the best animal system in the world for research in this area. Our research on maternal-embryonic interactions in this animal model has direct implicatio ....Plasticity in placental vasculature and the evolution of viviparity in lizards. This cross-disciplinary research will provide thorough understanding of the reproductive physiology of animals with different forms of reproduction, information critical for conservation and management of Australia's biodiversity. Australia's unique reptiles provide the best animal system in the world for research in this area. Our research on maternal-embryonic interactions in this animal model has direct implications for understanding some medical disorders, such as human angiogenic disorders. The research will strengthen ties internationally through research in South Africa, and provide training in combined biological and medical technologies. It will maintain Australia's long-term leadership in this area of research.Read moreRead less
The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and ....The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and damaged proteins. This work is important because some diseases (eg, Alzheimers disease) involve the toxic effects of abnormal protein precipitation. Understanding how clusterin works may help in developing better treatments for these diseases.Read moreRead less
Transduction of neuronal signals by brain macroglial cells: implications for neuronal function. Study of mechanisms regulating brain cell (neuron and glial) communication is essential for understanding of normal brain function and transformations that occur in neurodegenerative states and age-related disorders. Mechanisms underlying neuron-glia communication are not well understood. By combining cell physiology, digital imaging technologies, and genetically designed and delivered molecules we w ....Transduction of neuronal signals by brain macroglial cells: implications for neuronal function. Study of mechanisms regulating brain cell (neuron and glial) communication is essential for understanding of normal brain function and transformations that occur in neurodegenerative states and age-related disorders. Mechanisms underlying neuron-glia communication are not well understood. By combining cell physiology, digital imaging technologies, and genetically designed and delivered molecules we will enhance our understanding of this brain cell communication and critical roles played by intracellular calcium. This will enhance international competitiveness of Australian biological research and provide novel insight of glial function in neurodegeneration and potential for specific therapeutic intervention in disease.Read moreRead less
Calcium regulation in the skeletal muscle triad and along the fibre. The fundamental role of skeletal muscle is posture and movement. Alterations in the normal way calcium regulates skeletal muscle function in fatigue, age and disease states causes loss of normal function. Preventing or controlling these changes is a key therapeutic aim. However, we currently lack full understanding of key mechanisms of calcium regulation in healthy skeletal muscle. This project will define key aspects of cal ....Calcium regulation in the skeletal muscle triad and along the fibre. The fundamental role of skeletal muscle is posture and movement. Alterations in the normal way calcium regulates skeletal muscle function in fatigue, age and disease states causes loss of normal function. Preventing or controlling these changes is a key therapeutic aim. However, we currently lack full understanding of key mechanisms of calcium regulation in healthy skeletal muscle. This project will define key aspects of calcium regulation that could be crucial to developing targets for improving function of skeletal muscle under stressed states.Read moreRead less
Competition between regulatory processes in Amphibians: Testing the effects of physical and physiological factors on thermoregulation and hydroregulation. Regulation of body temperature is important for many animals, and it influences processes such as growth and reproduction. However, it is not clear to what extent wet-skinned animals can control body temperature because of evaporation. Understanding this about frogs is crucial to understanding their habitat requirements and the effects of clim ....Competition between regulatory processes in Amphibians: Testing the effects of physical and physiological factors on thermoregulation and hydroregulation. Regulation of body temperature is important for many animals, and it influences processes such as growth and reproduction. However, it is not clear to what extent wet-skinned animals can control body temperature because of evaporation. Understanding this about frogs is crucial to understanding their habitat requirements and the effects of climate change, habitat modification, and the invasion of cane toads on their populations. Amphibians are in decline worldwide, and research into the basic ways that these animals interact with the physical environment is needed before effective management plans can be produced. The unique physiological characteristics of Australian frogs make this is the best place in the world to do this research.Read moreRead less
Novel regulation of TRP channels by oxygen-dependent hydroxylation. Factor inhibiting HIF-1 (FIH-1) is an oxygen-sensing asparaginyl hydroxylase. A bioinformatic search identified specific transient receptor potential (TRP) ion channels as likely substrates. The hypothesis is that TRP channels are regulated by hypoxia, mediated through a novel mechanism of oxygen-dependent hydroxylation by FIH. The aim of this project is to investigate how hydroxylation by FIH mediates the hypoxic regulation of ....Novel regulation of TRP channels by oxygen-dependent hydroxylation. Factor inhibiting HIF-1 (FIH-1) is an oxygen-sensing asparaginyl hydroxylase. A bioinformatic search identified specific transient receptor potential (TRP) ion channels as likely substrates. The hypothesis is that TRP channels are regulated by hypoxia, mediated through a novel mechanism of oxygen-dependent hydroxylation by FIH. The aim of this project is to investigate how hydroxylation by FIH mediates the hypoxic regulation of TRP channels. Preliminary data show that the first candidate, TRPV3, is activated in hypoxia, is hydroxylated by FIH, and hydroxylation mediates changes in activity. Ion channels are important for the physiological response to hypoxia, and this project aims to define a novel mechanism for this response, with relevance to mammalian physiology.Read moreRead less
Do frogs hydroregulate? Regulation versus tolerance of thermal and hydric states. Amphibians are in decline in Australia and worldwide. Frogs are a middle link in terrestrial and aquatic food chains (as predators and prey) so are important for the sustainability of Australia's biodiversity and as indicators of environmental problems. Basic research about the ways Australian frogs interact with the physical environment to balance body water and temperature is crucial to predicting the effects of ....Do frogs hydroregulate? Regulation versus tolerance of thermal and hydric states. Amphibians are in decline in Australia and worldwide. Frogs are a middle link in terrestrial and aquatic food chains (as predators and prey) so are important for the sustainability of Australia's biodiversity and as indicators of environmental problems. Basic research about the ways Australian frogs interact with the physical environment to balance body water and temperature is crucial to predicting the effects of climate change or habitat modification on frogs. This basic information is needed to produce effective conservation plans for native frogs and management plans for invasive cane toads. We will train students in techniques and concepts in ecology, conservation biology, and animal physiology.Read moreRead less
Responses of reptiles to fluctuating thermal environments: behaviour or biochemistry? I propose a conceptual shift in the way thermal physiology of reptiles is interpreted, questioning the predominant role of behaviour in reptilian thermoregulation. I will test the hypothesis that changes in cellular biochemistry are an important mechanism by which reptiles respond to environmental fluctuations. I will determine the relationship between metabolic enzyme activity and performance functions, and ....Responses of reptiles to fluctuating thermal environments: behaviour or biochemistry? I propose a conceptual shift in the way thermal physiology of reptiles is interpreted, questioning the predominant role of behaviour in reptilian thermoregulation. I will test the hypothesis that changes in cellular biochemistry are an important mechanism by which reptiles respond to environmental fluctuations. I will determine the relationship between metabolic enzyme activity and performance functions, and the results may call for a re-assessment of current concepts such as the notion that reptiles must achieve "preferred" body temperatures to maintain performance.Read moreRead less