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
The grand challenge of predicting human movement energetics. This Project aims to advance our understanding of how the neuromuscular system uses energy during movement by exploring the interplay of different factors that influence movement energetics. The Project will explore different levels of organisation; from how muscle fibres consume energy to how those fibres interact and are subsequently controlled within a complex neuromuscular system. Expected outcomes of this Project will be an improv ....The grand challenge of predicting human movement energetics. This Project aims to advance our understanding of how the neuromuscular system uses energy during movement by exploring the interplay of different factors that influence movement energetics. The Project will explore different levels of organisation; from how muscle fibres consume energy to how those fibres interact and are subsequently controlled within a complex neuromuscular system. Expected outcomes of this Project will be an improved capacity to predict energy expenditure of the vast array of movements that humans perform. This will enable accurate monitoring of human energy expenditure and will provide benefits for individualised exercise prescription, enhancing work productivity or designing devices to augment human performance.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
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
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
Structural and neural determinants of stress and strain in human muscle. This project aims to further our understanding of the biomechanical stress and strains experienced by contracting human muscles. Using innovative imaging techniques such as microendoscopy and supersonic shear imaging, we expect to generate new significant evidence on the structural and neural factors that lead to areas of high stress in human muscles. Outcomes of this project include not only a new understanding of muscle d ....Structural and neural determinants of stress and strain in human muscle. This project aims to further our understanding of the biomechanical stress and strains experienced by contracting human muscles. Using innovative imaging techniques such as microendoscopy and supersonic shear imaging, we expect to generate new significant evidence on the structural and neural factors that lead to areas of high stress in human muscles. Outcomes of this project include not only a new understanding of muscle design on multi-scale level, but also of muscle function and adaptation. This should provide significant benefits in better predicting muscle injury and prescribing safe exercise, knowledge that would benefit biomechanical engineers and sport and exercise professionals.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
Design of the cardiovascular system of living and fossil vertebrates. This project aims to understand how the heart and blood vessels evolved in mammals, birds, reptiles and fish to achieve efficiency. The heart is the most important organ for life. The project will study the structure and function of vertebrate animals’ hollow and spongy hearts to show how energetics shaped their evolution. It will measure arterial holes in bone to gauge brain and bone metabolism, which opens up a new way to me ....Design of the cardiovascular system of living and fossil vertebrates. This project aims to understand how the heart and blood vessels evolved in mammals, birds, reptiles and fish to achieve efficiency. The heart is the most important organ for life. The project will study the structure and function of vertebrate animals’ hollow and spongy hearts to show how energetics shaped their evolution. It will measure arterial holes in bone to gauge brain and bone metabolism, which opens up a new way to measure metabolism in extinct animals directly from fossils, rather than by inference from living relatives. The expected outcome is to correlate cardiovascular design and metabolic rates of organs.Read moreRead less
A new model for animal growth. This project aims to test and further develop a new theory for how animals grow. The new growth theory brings together the fields of physiology, ecology, and evolutionary biology, generating research publications, and training students. The proposed research is anticipated to provide a fundamentally new means for understanding how animals divide energy among growth and reproduction, paving the way for organismal allocation to these processes to be optimised by sele ....A new model for animal growth. This project aims to test and further develop a new theory for how animals grow. The new growth theory brings together the fields of physiology, ecology, and evolutionary biology, generating research publications, and training students. The proposed research is anticipated to provide a fundamentally new means for understanding how animals divide energy among growth and reproduction, paving the way for organismal allocation to these processes to be optimised by selective breeding or genetic manipulation, yielding potential benefits for aquaculture (enhanced growth) or re-introduction (enhanced reproduction).Read moreRead less
The recirculation of myeloid dendritic cells. This project aims to understand dendritic cell recirculation. It will use virological tools to track dendritic cell migration, and identify key decision points. Expected outcomes include enhanced capacity in basic research and greater interdisciplinary collaboration between virology and immunology research groups. Significant benefits will include a new understanding of how G protein coupled receptor signalling and other tissue cues guide dendritic c ....The recirculation of myeloid dendritic cells. This project aims to understand dendritic cell recirculation. It will use virological tools to track dendritic cell migration, and identify key decision points. Expected outcomes include enhanced capacity in basic research and greater interdisciplinary collaboration between virology and immunology research groups. Significant benefits will include a new understanding of how G protein coupled receptor signalling and other tissue cues guide dendritic cell recirculation, and what consequences the recirculation has for immune cell function. This understanding will significantly advance our basic understanding of the immune system.Read moreRead less