Iron accumulation in the nematode C.elegans: a model of ageing. This project will investigate the role of biological metals in the process of ageing, the causes of which remain unresolved. The practical outcomes for society are broad; beyond improving understandings of the basic biology of ageing, this study will provide new insight and approaches that can be used to optimise lifespan.
Novel mechanisms for regulating the retinal vasculature. Tight control of the retinal vasculature is crucial for maintaining normal vision. Unlike most blood vessels in the body, those in the retina and brain receive no direct neural control. Rather they rely on support cells to communicate the needs of neurons. This project aims to examine the mechanisms by which resident immune cells, called microglia, regulate retinal capillaries in response to neural activity. New knowledge examining a novel ....Novel mechanisms for regulating the retinal vasculature. Tight control of the retinal vasculature is crucial for maintaining normal vision. Unlike most blood vessels in the body, those in the retina and brain receive no direct neural control. Rather they rely on support cells to communicate the needs of neurons. This project aims to examine the mechanisms by which resident immune cells, called microglia, regulate retinal capillaries in response to neural activity. New knowledge examining a novel mechanism will be generated. This information is crucial for enhancing our understanding of how blood vessels are controlled in the retina and brain and will guide the development of novel ways of examining blood vessel function.Read moreRead less
Defining how serotonin regulates gut motility. This project aims to deepen knowledge of gastrointestinal physiology, and reveal the mechanisms by which the major gastrointestinal signalling molecule, serotonin, regulates gut peristalsis. Almost all of the serotonin in our body is made in the gastrointestinal tract where it controls many functions, including how our gut wall contracts during peristalsis. Proper control of gut peristalsis and the transit of material through our bowel is important ....Defining how serotonin regulates gut motility. This project aims to deepen knowledge of gastrointestinal physiology, and reveal the mechanisms by which the major gastrointestinal signalling molecule, serotonin, regulates gut peristalsis. Almost all of the serotonin in our body is made in the gastrointestinal tract where it controls many functions, including how our gut wall contracts during peristalsis. Proper control of gut peristalsis and the transit of material through our bowel is important for our health. This project expects to define how serotonin controls peristalsis, where in the bowel this serotonin comes from, how serotonin communicates with the nervous system in our gastrointestinal tract, and how the cells that synthesise gut serotonin respond to contraction to trigger the secretion of serotonin.Read moreRead less
Microfluidic models of the CNS: Understanding cells, circuits & synapses. Aims: We aim to develop new cell culture platforms to form defined networks of brain cells. These platforms will be used to determine the critical mechanisms underpinning central nervous system function.
Significance: The devices developed will enable an unprecedented capacity to monitor changes throughout a network, with analysis at the level of the synapse, cell and circuit.
Expected outcomes: We will advance knowledge ....Microfluidic models of the CNS: Understanding cells, circuits & synapses. Aims: We aim to develop new cell culture platforms to form defined networks of brain cells. These platforms will be used to determine the critical mechanisms underpinning central nervous system function.
Significance: The devices developed will enable an unprecedented capacity to monitor changes throughout a network, with analysis at the level of the synapse, cell and circuit.
Expected outcomes: We will advance knowledge regarding the function of the CNS and deliver complex human cellular systems, that have both discovery and commercial applications.
Benefit: These platforms will have subsequent application revealing the mechanisms underlying numerous neurological diseases, with capacity to upscale for rapid drug screening.
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Molecular control of postnatal heart development. This project aims to improve our understanding of how the heart develops after birth and the molecules that control this process. Recent advances in tissue engineering have opened up opportunities for the generation of synthetic tissues but these studies have also highlighted a fundamental knowledge gap in our understanding of how complex tissues mature to prepare for life as an adult. Much is known about the molecules that control early embryoni ....Molecular control of postnatal heart development. This project aims to improve our understanding of how the heart develops after birth and the molecules that control this process. Recent advances in tissue engineering have opened up opportunities for the generation of synthetic tissues but these studies have also highlighted a fundamental knowledge gap in our understanding of how complex tissues mature to prepare for life as an adult. Much is known about the molecules that control early embryonic development but little is known about the molecules that control maturation after birth. This project aims to build new knowledge that is expected to improve our ability to generate mature heart muscle cells for stem cell applications, tissue repair and regeneration.Read moreRead less
Muscling in on the brain. This project investigates an enzyme that 'matures' neurotransmitters in the brain that regulate food intake, energy expenditure and blood pressure by the brain; these neurotransmitters arise from the same precursor molecule. This project will show the physiological relevance of this enzyme in obesity.
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
Advancing knowledge of microbial symbioses underpinning coral health and reef resilience and predicting their responses to climate change. Coral reefs are complex, diverse ecosystems in which microbial communities form associations with host corals. However, the roles these associations play in coral stress responses are unknown. This project unlocks the black-box of coral microbial complexity and determines how the reef’s smallest members have the greatest influence on reef health.
Skeletal endocrine signalling in the regulation of glucose metabolism. This project seeks to explore a highly novel and interesting recent development in bone biology: the fact that the skeleton is a central regulator of glucose metabolism. Currently, the mechanisms involved in this process remain unclear. mTORC1 has been identified as a signalling pathway in bone cells that modulates glucose metabolism. This project plans to selectively delete mTORC1 in the bone cells of mice to examine how ske ....Skeletal endocrine signalling in the regulation of glucose metabolism. This project seeks to explore a highly novel and interesting recent development in bone biology: the fact that the skeleton is a central regulator of glucose metabolism. Currently, the mechanisms involved in this process remain unclear. mTORC1 has been identified as a signalling pathway in bone cells that modulates glucose metabolism. This project plans to selectively delete mTORC1 in the bone cells of mice to examine how skeletal mTORC1 signalling regulates glucose metabolism, and identify novel pathways and circulating factors involved in this process. These studies may provide greater understanding of the basic biology of glucose metabolism, and may have applications in animal husbandry and the future management of diabetes.Read moreRead less
Aquaporin channels in cell migration. The project aims to determine the role of Aquaporin1 (AQP1) in enhancing rapid cell motility. Cell migration is important for development, repair, and protection in multicellular organisms. AQP1 is increased in some rapidly migrating cell types. Loss of AQP1 impairs migration, which is restored by reintroduction of AQP1 but not AQP4. Expected outcomes include defining the features of AQP1 that confer enhanced cell migration. The project will test the hypothe ....Aquaporin channels in cell migration. The project aims to determine the role of Aquaporin1 (AQP1) in enhancing rapid cell motility. Cell migration is important for development, repair, and protection in multicellular organisms. AQP1 is increased in some rapidly migrating cell types. Loss of AQP1 impairs migration, which is restored by reintroduction of AQP1 but not AQP4. Expected outcomes include defining the features of AQP1 that confer enhanced cell migration. The project will test the hypothesis that dual water and ion channel functions of AQP1 are needed for movement, using migration assays in cells with wild type and mutant AQP1, and selective pharmacological agents developed by the project team to dissect the essential channel properties that enable rapid migration in cancer and stem cells. The project seeks to build knowledge of AQP roles in development, regeneration and surveillance, potentially improving health care by revealing pathways in migration disorders such as metastasis.Read moreRead less