How Spinal Afferent Neurons Control Appetite and Thirst . This project aims to provide major new insights about how the gut communicates with the brain, to regulate how much food and fluids have been consumed. The proposal expects to generate new knowledge about gut-brain communication and how one of the major sensory nerves from the gut relays information about thirst and appetite sensations. The project addresses fundamental questions that rely on techniques only recently developed in our labo ....How Spinal Afferent Neurons Control Appetite and Thirst . This project aims to provide major new insights about how the gut communicates with the brain, to regulate how much food and fluids have been consumed. The proposal expects to generate new knowledge about gut-brain communication and how one of the major sensory nerves from the gut relays information about thirst and appetite sensations. The project addresses fundamental questions that rely on techniques only recently developed in our laboratory. We expect to demonstrate a major new sensory nerve pathway from the gut to the brain that plays a major role in appetite and thirst sensations. We will learn how gut to brain communication underlies the feeling of "fullness" when people consume food and drink.
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Age-related mechanisms of amino acid signalling in skeletal muscle. This project aims to increase our understanding of the role of glycine receptor-mediated signalling and its metabolism in the amino acid sensing capacity of mTORC1, a key enzyme regulating muscle protein synthesis. Ageing is associated with a progressive decline in skeletal muscle mass, weakness, and impaired regeneration after injury. Impaired anabolic signalling after food intake has been proposed as a key contributor, yet the ....Age-related mechanisms of amino acid signalling in skeletal muscle. This project aims to increase our understanding of the role of glycine receptor-mediated signalling and its metabolism in the amino acid sensing capacity of mTORC1, a key enzyme regulating muscle protein synthesis. Ageing is associated with a progressive decline in skeletal muscle mass, weakness, and impaired regeneration after injury. Impaired anabolic signalling after food intake has been proposed as a key contributor, yet the metabolic pathways responsible for nutrient sensing and regulation of protein synthesis remain unresolved. The project will assess defective amino acid sensing and protein synthesis in old mammals, identifying the role of glycine signalling in these processes. The project expects to underpin development of muscle-specific modulators of muscle homeostasis with broad relevance to Australia’s ageing population.Read moreRead less
Activity-based chemogenetics: a novel approach to modulating brain function. Aim: To unravel the astounding complexity of the vertebrate brain by developing a completely novel method, that enables manipulation of the activity of defined nerve cells to study behaviour. Significance: Such technical advances are essential for understanding the intricate function of the brain. Expected outcomes: We will provide a technical advance of broad scope that will lead to novel neuroscience throughout the wo ....Activity-based chemogenetics: a novel approach to modulating brain function. Aim: To unravel the astounding complexity of the vertebrate brain by developing a completely novel method, that enables manipulation of the activity of defined nerve cells to study behaviour. Significance: Such technical advances are essential for understanding the intricate function of the brain. Expected outcomes: We will provide a technical advance of broad scope that will lead to novel neuroscience throughout the world. We will also increase understanding of body weight control through the experiments planned to validate our tool. Benefit: Our technical advance has the potential to alter experimental protocols, and the information obtained by experimental neuroscience, across all areas attempting to understand brain function.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
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