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
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
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
Heat regulation by the fibre types in muscle. 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 fibre types that make up skeletal muscles regulate heat generation against other muscle function, to maintain core body temperature and the normal movement and posture of the mammal. Project outcomes include defining, for the first time, how heat generation in the muscles o ....Heat regulation by the fibre types in muscle. 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 fibre types that make up skeletal muscles regulate heat generation against other muscle function, to maintain core body temperature and the normal movement and posture of the mammal. 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 with achieving a desired meat quality and yield in beef and other commercially important animals.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
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
Sinusoidal voltage protocols for characterisation of ion channel kinetics. This project aims to implement an innovative approach to modelling ion channel behaviour that employs short, information-rich datasets and parameter inference. Using the hERG potassium channel as a test case, the project will show that this approach is more efficient than current methods and outperforms all published models in independent validations. The project aims to extend on initial implementation to probe the therm ....Sinusoidal voltage protocols for characterisation of ion channel kinetics. This project aims to implement an innovative approach to modelling ion channel behaviour that employs short, information-rich datasets and parameter inference. Using the hERG potassium channel as a test case, the project will show that this approach is more efficient than current methods and outperforms all published models in independent validations. The project aims to extend on initial implementation to probe the thermodynamics and pharmacology of ion channel gating. The anticipated outcomes are to grow fundamental knowledge of ion channel biophysics and ability to probe ion channel function in silico. The project will build on an emerging collaboration between international leaders in physiology, pharmacology, mathematics and computer modelling. The methodology and fundamental knowledge generated will significantly advance our understanding of the physiology and biophysics of ion channels, while the application of the method will have direct impact in the pharmaceutical industry and regulatory science.Read moreRead less
Understanding uterine contractility for reducing newborn lamb mortality. The project aims to elucidate the mechanisms underlying normal and dysfunctional uterine contractions in labouring ewes. Significantly, ~20% of newborn lambs die within days of birth, costing the Australian sheep industry more than $780 million annually. Difficult lambing is the leading cause of lamb mortality and weak uterine contractions are the most important contributor to difficult labour (dystocia). Intended outcomes ....Understanding uterine contractility for reducing newborn lamb mortality. The project aims to elucidate the mechanisms underlying normal and dysfunctional uterine contractions in labouring ewes. Significantly, ~20% of newborn lambs die within days of birth, costing the Australian sheep industry more than $780 million annually. Difficult lambing is the leading cause of lamb mortality and weak uterine contractions are the most important contributor to difficult labour (dystocia). Intended outcomes include a better understanding of dysfunctional labour contractions in sheep, and this knowledge could then contribute to the identification of more specific targets for genetic testing for dystocia. The benefits should include more specific aids for selective breeding programs for improved productivity and profitability.Read moreRead less
Multiscale and multimodal modelling of brain dynamics. This project aims to understand dynamics of how several brain regions work together to process information. This project will generate new knowledge in brain sciences by using state of the art computational modelling and neuroimaging methods like functional and diffusion magnetic resonance imaging and electromagnetic measurements. This project will develop technologies to compute multiscale, multimodal and directed connectivity in the brain. ....Multiscale and multimodal modelling of brain dynamics. This project aims to understand dynamics of how several brain regions work together to process information. This project will generate new knowledge in brain sciences by using state of the art computational modelling and neuroimaging methods like functional and diffusion magnetic resonance imaging and electromagnetic measurements. This project will develop technologies to compute multiscale, multimodal and directed connectivity in the brain. Expected outcomes of this project will enhance our understanding of the brain’s functional organization and dynamics. The benefits of this project will include breakthroughs in development of new neuro-technologies like brain-machine interfaces and neuroscience inspired artificial intelligence. Read moreRead less
Revealing the mechanobiology of neural tube formation. This project aims to understand the formation of the neural tube; a fundamental tissue structure that generates the brain and the spinal cord. Using interdisciplinary approaches and exploiting recent advances in transgenic and imaging technologies, we expect to reveal the complex interplay between cells and their environment that generates mechanical forces to direct neural tissue formation. Outcomes include knowledge of previously intractab ....Revealing the mechanobiology of neural tube formation. This project aims to understand the formation of the neural tube; a fundamental tissue structure that generates the brain and the spinal cord. Using interdisciplinary approaches and exploiting recent advances in transgenic and imaging technologies, we expect to reveal the complex interplay between cells and their environment that generates mechanical forces to direct neural tissue formation. Outcomes include knowledge of previously intractable developmental processes, training of future scientists and development of international collaborations. This should provide enhanced imaging capacity, a higher quality scientific workforce and position Australia at the forefront of cell and developmental biology.Read moreRead less