Visualising vascular adaptation at the micro-scale in humans. The project aims to investigate fundamental issues in the mechanisms underlying vascular remodelling. It plans to develop novel optical scanning techniques to acquire high-resolution images of the cutaneous microvasculature, alongside absolute blood flow quantification. These novel tools would allow us to visualise and quantify functional and structural adaptations in the microvasculature in response to physiological stimuli such as h ....Visualising vascular adaptation at the micro-scale in humans. The project aims to investigate fundamental issues in the mechanisms underlying vascular remodelling. It plans to develop novel optical scanning techniques to acquire high-resolution images of the cutaneous microvasculature, alongside absolute blood flow quantification. These novel tools would allow us to visualise and quantify functional and structural adaptations in the microvasculature in response to physiological stimuli such as heat exposure and exercise. The non-invasive tool aims to enable us to assess adaptations in microvasculature health, improving our understanding of cardiovascular diseases and type 2 diabetes and potentially reducing the impact of costly and debilitating morbidities such as nephropathy, neuropathy, retinopathy, impotence and skin ulceration.Read moreRead less
Biological Role of Contraction-Induced Heat Shock Protein Expression. It is well known that mammalian skeletal muscle increases its expression of a group of highly conserved proteins, the heat shock proteins (HSP) in response to repeated contraction. However, the biological role of this expression is unclear. The aim of this project is to determine the biological role of contraction-induced HSP expression. We expect to show that HSP synthesis in response to exercise has three major roles; 1) to ....Biological Role of Contraction-Induced Heat Shock Protein Expression. It is well known that mammalian skeletal muscle increases its expression of a group of highly conserved proteins, the heat shock proteins (HSP) in response to repeated contraction. However, the biological role of this expression is unclear. The aim of this project is to determine the biological role of contraction-induced HSP expression. We expect to show that HSP synthesis in response to exercise has three major roles; 1) to act to repair damaged proteins in recovery from muscle injury 2) to act as a "molecular motor" to translocate proteins from one region of a muscle cell to another and 3) to be released into the circulation in order to act as a central signal to activate immune cells. Such a project will be significant because it will allow for a fundamental understanding as to why these proteins are produced in response to exercise. We expect to enhance our understanding of fundamental cell biology.Read moreRead less
Impact of shear stress on vascular adaptations in humans. Large arteries are important for the delivery of blood and oxygen to organs such as the heart and brain. A primary physiological stimulus which controls the size and function of these crucial arteries is the magnitude of flow or, more accurately, shear force that the inner wall of the artery is exposed to. We have developed novel software which enables non-invasive assessment of arterial wall velocity, diameter and blood flow. We will ass ....Impact of shear stress on vascular adaptations in humans. Large arteries are important for the delivery of blood and oxygen to organs such as the heart and brain. A primary physiological stimulus which controls the size and function of these crucial arteries is the magnitude of flow or, more accurately, shear force that the inner wall of the artery is exposed to. We have developed novel software which enables non-invasive assessment of arterial wall velocity, diameter and blood flow. We will assess the impact of acute and chronic changes in wall flow and shear on arterial size and function. We will also develop new software which measures other aspects of artery wall behaviour. These basic human physiology studies have direct implications for assessment of artery health in humans.Read moreRead less
A microfluidic approach to study the mechanobiology of ageing blood vessels. This project aims to study the effect of the stiffening of ageing arteries in endothelial cells. It explores the changes that occur in endothelial cells using a unique microfluidic technology with tuneable wall stiffness to mimic the biophysical and biochemical properties of ageing arteries. The expected outcome is the identification of the cellular mechanisms that control endothelial responses to arterial stiffening. T ....A microfluidic approach to study the mechanobiology of ageing blood vessels. This project aims to study the effect of the stiffening of ageing arteries in endothelial cells. It explores the changes that occur in endothelial cells using a unique microfluidic technology with tuneable wall stiffness to mimic the biophysical and biochemical properties of ageing arteries. The expected outcome is the identification of the cellular mechanisms that control endothelial responses to arterial stiffening. This should provide the fundamental knowledge required to assist in the development of new therapies to tackle age-related conditions such as cardiovascular disease and dementia.Read moreRead less
ZnT-1 regulates store operated calcium channels in salivary gland physiology and pathology. This project examines the hypothesis that the membrane protein ZnT-1 protects cardiac cells against the damage inflicted during ischemic reperfusion incidents, like in myocardial infarction (MI). The project is expected to elucidate the mechanism underlying cardiac cell protection, leading to the discovery of new drugs for protecting the heart against MI.
Defining the direct effects of exercise on arterial adaptation. Understanding the mechanisms responsible for the beneficial effects of exercise is fundamental to optimising the design of preventative programs aimed at healthy ageing. These experiments will contribute to our understanding of the direct effects of changes in blood flow and pressure during exercise on vascular adaptations in humans.
Environmental Control of Developmental Plasticity of Vertebrate Cardio-Pulmonary Systems. Our research will generate the first comprehensive picture of how environmental conditions are transduced to control the development of the vertebrate respiratory and cardiovascular systems over the perinatal period. The research will demonstrate how physiological systems are modified and hence evolve. Moreover, understanding the developmental pathology in embryos induced by changing environmental condition ....Environmental Control of Developmental Plasticity of Vertebrate Cardio-Pulmonary Systems. Our research will generate the first comprehensive picture of how environmental conditions are transduced to control the development of the vertebrate respiratory and cardiovascular systems over the perinatal period. The research will demonstrate how physiological systems are modified and hence evolve. Moreover, understanding the developmental pathology in embryos induced by changing environmental conditions (especially exposure to steroid-like pollutants) is crucial to support breeding programs of endangered species and may improve veterinary and medicinal treatment of premature animals and humans. This multi-disciplinary, international collaboration provides an international training ground and two-way exchange of students and postdocs.Read moreRead less
Coping With Pressure: Respiratory Biology of Marine Mammals. Many marine mammals undergo severe, protracted lung collapse during deep dives. They also exhibit prolonged periods of apnea during sleep. In humans, lung collapse and sleep apnea both represent severe respiratory dysfunction. Pulmonary surfactant, a complex mixture that lines the lung, stabilises the lungs in terrestrial mammals, preventing lung collapse. Here, we propose a comprehensive examination of respiratory function in marine m ....Coping With Pressure: Respiratory Biology of Marine Mammals. Many marine mammals undergo severe, protracted lung collapse during deep dives. They also exhibit prolonged periods of apnea during sleep. In humans, lung collapse and sleep apnea both represent severe respiratory dysfunction. Pulmonary surfactant, a complex mixture that lines the lung, stabilises the lungs in terrestrial mammals, preventing lung collapse. Here, we propose a comprehensive examination of respiratory function in marine mammals. This study will significantly advance our knowledge of the diving physiology of Australian marine mammals. A detailed examination of the respiratory and surfactant systems of marine mammals may also reveal adaptations that enable these animals to endure sleep apnea and lung collapse.Read moreRead less
Modulating the molecular and cellular physiology of ageing skeletal muscle. Understanding the underlying mechanisms of how ageing affects muscle is of increasing importance to the community as the number of older persons in the population continues to escalate and the age of retirement increases. Old muscles are slower and weaker than young muscles, and are more easily injured. This proposal is focussed on developing safe therapies to prevent or reverse these age-related effects. Making old musc ....Modulating the molecular and cellular physiology of ageing skeletal muscle. Understanding the underlying mechanisms of how ageing affects muscle is of increasing importance to the community as the number of older persons in the population continues to escalate and the age of retirement increases. Old muscles are slower and weaker than young muscles, and are more easily injured. This proposal is focussed on developing safe therapies to prevent or reverse these age-related effects. Making old muscles young again, is a research strategy that will promote healthy ageing and enable older Australians to enjoy a better quality of life.Read moreRead less
Brain temperature regulation in mammals: mechanisms and consequences. Mammals detect increases in body temperature predominantly in the brain. Counterintuitively many mammals selectively cool the brain during heat stress, which appears to defeat the mechanism for inducing cooling responses. We intend to investigate this apparent anomaly which we believe is concerned with optimizing water use in hot conditions. We will further investigate the source of water for evaporative cooling by panting and ....Brain temperature regulation in mammals: mechanisms and consequences. Mammals detect increases in body temperature predominantly in the brain. Counterintuitively many mammals selectively cool the brain during heat stress, which appears to defeat the mechanism for inducing cooling responses. We intend to investigate this apparent anomaly which we believe is concerned with optimizing water use in hot conditions. We will further investigate the source of water for evaporative cooling by panting and discover if there has been convergent evolution in thermoregulatory strategies in the eutherian and marsupial lineages. The data we collect will be used to support a new model for thermoregulation in mammals.
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