Physiology of oxygen transport in the mammalian kidney. This project aims to improve understanding of oxygen regulation in renal tissue and knowledge of the physiology of the kidney. The mammalian kidney receives more oxygen than it uses or needs, and yet renal tissue is commonly found to be hypoxic. This project proposes that oxygen transport to the renal tissue is limited by blood vessel surface area. The project expects to generate anatomical data currently missing from the renal physiology c ....Physiology of oxygen transport in the mammalian kidney. This project aims to improve understanding of oxygen regulation in renal tissue and knowledge of the physiology of the kidney. The mammalian kidney receives more oxygen than it uses or needs, and yet renal tissue is commonly found to be hypoxic. This project proposes that oxygen transport to the renal tissue is limited by blood vessel surface area. The project expects to generate anatomical data currently missing from the renal physiology community, and potentially change the accepted story of oxygen homeostasis in the kidney. This will provide significant benefits, such as the provision of the foundational physiological science behind a determinant of kidney health and its flow-on impact to quality of life.Read moreRead less
Anandamide activated chloride channels in sensory neurons. We are seeking to understand how the nerve cells that sense our environment are regulated by signalling molecules produced by our body. Understanding how these cells function in normal conditions is essential as basis for understanding how they may function abnormally in physically stressful situations or in chronic pain conditions. The work may eventually lead to better treatments for a wide range of disorders that involve the sensory ....Anandamide activated chloride channels in sensory neurons. We are seeking to understand how the nerve cells that sense our environment are regulated by signalling molecules produced by our body. Understanding how these cells function in normal conditions is essential as basis for understanding how they may function abnormally in physically stressful situations or in chronic pain conditions. The work may eventually lead to better treatments for a wide range of disorders that involve the sensory nervous system. Read moreRead less
Intracellular calcium in intact muscle during fatigue and stretch-induced damage. Confocal microscopes can investigate intact tissues during normal function. We will develop and apply this novel approach to muscle. We expect this new approach to become a fundamental new tool for exploring muscle function under near normal conditions. Muscle pain and weakness are common disabilities in humans and we expect this new approach to provide insights into the causes and treatment of these common cond ....Intracellular calcium in intact muscle during fatigue and stretch-induced damage. Confocal microscopes can investigate intact tissues during normal function. We will develop and apply this novel approach to muscle. We expect this new approach to become a fundamental new tool for exploring muscle function under near normal conditions. Muscle pain and weakness are common disabilities in humans and we expect this new approach to provide insights into the causes and treatment of these common conditions.Read moreRead less
Resurgent Sodium Currents in Peripheral Nerve Axons and Sensory Neurones. This project seeks evidence that unusual gating of sodium channels contributes to the hyperexcitability that results in spontaneous impulse activity in sensory axons. It asks whether axons normally behave as if they have this gating mode, whether it can be induced, whether any such behaviour is more prominent with sensory axons than motor, and whether the current can be measured directly in sensory neurones. The project is ....Resurgent Sodium Currents in Peripheral Nerve Axons and Sensory Neurones. This project seeks evidence that unusual gating of sodium channels contributes to the hyperexcitability that results in spontaneous impulse activity in sensory axons. It asks whether axons normally behave as if they have this gating mode, whether it can be induced, whether any such behaviour is more prominent with sensory axons than motor, and whether the current can be measured directly in sensory neurones. The project is the first to involve correlation of patch-clamp recordings with the behaviour of intact axons. Its outcomes will affect thought about sodium channel behaviour and may alter approaches to disorders of axonal excitability.Read moreRead less
Sarcoplasmic reticulum-mitochondrial functional interactions in muscle. Muscle in the body of animals and human has the ability to adapt to stress placed on it, to improve performance. This allows new physical tasks that have been unfamiliar to become easier. One form of stress on the muscle is the demand to work longer without fatigue. This can be important for animal survival or athletes training for sport. A single session of intense muscle contractions can lead to the muscle increasing its c ....Sarcoplasmic reticulum-mitochondrial functional interactions in muscle. Muscle in the body of animals and human has the ability to adapt to stress placed on it, to improve performance. This allows new physical tasks that have been unfamiliar to become easier. One form of stress on the muscle is the demand to work longer without fatigue. This can be important for animal survival or athletes training for sport. A single session of intense muscle contractions can lead to the muscle increasing its capacity for endurance within 24 hrs. This project aims to examine this phenomenon in animals and human to decipher the mechanism involved in the beneficial muscle changes experienced in such a brief time. It will provide benefits such as the potential to manipulate human muscle condition and animal muscle (meat) quality.Read moreRead less
Physiological activation and targets of calcium signaling in muscle. The skeletal muscle fibre is a highly specialised cell for the rapid delivery of calcium to elicit contraction, required for posture, movement and thus one's independence. Calcium is also a signal for other purposes, such as triggering other processes within the muscle for its own maintenance. These calcium signals are poorly understood. This project aims to determine when the calcium signals are turned on during normal muscle ....Physiological activation and targets of calcium signaling in muscle. The skeletal muscle fibre is a highly specialised cell for the rapid delivery of calcium to elicit contraction, required for posture, movement and thus one's independence. Calcium is also a signal for other purposes, such as triggering other processes within the muscle for its own maintenance. These calcium signals are poorly understood. This project aims to determine when the calcium signals are turned on during normal muscle activity and what the end result of the signals is for the muscle.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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The comparative physiology of oxygen delivery to the kidney. The kidney is in danger of hyperoxia because the kidney receives so much blood relative to its mass. It is proposed that shunting oxygen between arteries and veins substantially mitigates the risk of hyperoxia, but under certain circumstances shunting substantially increases the risk of kidney hypoxia. Using a combination of synchrotron and histological imaging, This project will carefully define the three-dimensional vasculature of th ....The comparative physiology of oxygen delivery to the kidney. The kidney is in danger of hyperoxia because the kidney receives so much blood relative to its mass. It is proposed that shunting oxygen between arteries and veins substantially mitigates the risk of hyperoxia, but under certain circumstances shunting substantially increases the risk of kidney hypoxia. Using a combination of synchrotron and histological imaging, This project will carefully define the three-dimensional vasculature of the renal cortex in several different species and interpret its functional significance using computational modeling. The outcome of this project will be a new understanding in the comparative physiology of oxygen transport and shunting in the kidney.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
Investigating the mechanisms of flavonoid actions on glycine receptors. The research to be conducted in this project will use state-of-the-art electrophysiological and molecular biological approaches to carefully characterise the actions of certain flavonoid compounds on the glycine-receptor channel. These compounds have recently been reported to act as modulators of ligand-gated ion channels, proteins integral to brain function and disease. However, no-one has studied in any detail the mechan ....Investigating the mechanisms of flavonoid actions on glycine receptors. The research to be conducted in this project will use state-of-the-art electrophysiological and molecular biological approaches to carefully characterise the actions of certain flavonoid compounds on the glycine-receptor channel. These compounds have recently been reported to act as modulators of ligand-gated ion channels, proteins integral to brain function and disease. However, no-one has studied in any detail the mechanisms by which these compounds act. By discovering their site and mechanisms of action we will further our understanding of these important proteins and their modulation, maintain Australia's significant expertise in this field and provide leads for future development of drugs with potential therapeutic value.Read moreRead less