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
Understanding the mechanisms of GABA type-A receptor activation and drug modulation. There is currently little understanding of how sedative and anxiolytic drugs, including valium, interact with their receptors in the brain. This project will dramatically increase our understanding of how these receptors work and how drugs affect their activity. This will provide new insights into drug discovery and design.
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
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
Discovering nature's photonic devices to control light and heat. This project aims to discover how and why beetles and butterflies reflect near-infrared light. Reflection of near-infrared radiation may be critical to prevent overheating, yet its role in thermal protection remains largely unexplored. The project will integrate evolutionary biology, optical physics and biophysics to reveal the diversity, mechanism, function and evolution of near-infrared signatures. Expected outcomes include the d ....Discovering nature's photonic devices to control light and heat. This project aims to discover how and why beetles and butterflies reflect near-infrared light. Reflection of near-infrared radiation may be critical to prevent overheating, yet its role in thermal protection remains largely unexplored. The project will integrate evolutionary biology, optical physics and biophysics to reveal the diversity, mechanism, function and evolution of near-infrared signatures. Expected outcomes include the discovery of nature’s solutions to selection for both optical (camouflage, communication) and thermal functions. The project will have significant benefits such as creating opportunities to develop biomimetic and bioinspired materials to enhance energy efficiency, which will have significant economic and environmental benefits.Read moreRead less
Molecular force sensing mechanisms of PIEZO channels. The aim of this project is to characterise the gating mechanism of Piezo mechanosensitive ion channels recently identified in animals and humans. Mechanotransduction is ancient, as indicated by the presence of mechanosensitive channels in bacteria where these channels are activated by the bilayer mechanism according to the force-from-lipids paradigm possibly applicable to gating of the Piezo channels as well. Piezo channels play a crucial rol ....Molecular force sensing mechanisms of PIEZO channels. The aim of this project is to characterise the gating mechanism of Piezo mechanosensitive ion channels recently identified in animals and humans. Mechanotransduction is ancient, as indicated by the presence of mechanosensitive channels in bacteria where these channels are activated by the bilayer mechanism according to the force-from-lipids paradigm possibly applicable to gating of the Piezo channels as well. Piezo channels play a crucial role in senses of touch and pain, and mutations in Piezo1 have been shown to cause Xerocytosis – a hereditary genetic disorder manifested in haemolytic anemia. This project aims to help answer fundamental questions in mechanotransduction in vertebrates.Read moreRead less
Single vesicle dynamics and the control of secretion. This project investigates secretion and tests a new model for secretory control. Its outcomes will further our knowledge in this important area and may be significant in the longer term for the treatment of secretory diseases.
A thermodynamic pathway to intracellular delivery. Cells transmit information through molecules. By delivering foreign molecules into cells, such as DNA and proteins, it is possible to engineer and reprogram cells just like a computer. This proposal aims to develop a novel microfluidic device for intracellular delivery. The device will work by exposing cells to rapid thermal shock to generate transient disruptions in cell membranes and thereby enable influx of foreign molecules into cells. To un ....A thermodynamic pathway to intracellular delivery. Cells transmit information through molecules. By delivering foreign molecules into cells, such as DNA and proteins, it is possible to engineer and reprogram cells just like a computer. This proposal aims to develop a novel microfluidic device for intracellular delivery. The device will work by exposing cells to rapid thermal shock to generate transient disruptions in cell membranes and thereby enable influx of foreign molecules into cells. To understand how the method can be optimized, the thermodynamic pathway of membrane disruption will be investigated at a single cell level. The methods and insights arising from this project could eventually lead to novel, patentable and lower-cost health technologies.Read moreRead less