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
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
Understanding mechanisms of sex programming of cardiovascular development. The goal of this project is to track the influence of sex and sex hormones through crucial lifespan timepoints to define how specific patterns of gene signalling determine adult cardiovascular traits at cell, tissue and systems level. Sexually distinct cardiovascular traits are conserved across mammalian species. Early developmental events are known to be important in influencing later adult characteristics, but how adult ....Understanding mechanisms of sex programming of cardiovascular development. The goal of this project is to track the influence of sex and sex hormones through crucial lifespan timepoints to define how specific patterns of gene signalling determine adult cardiovascular traits at cell, tissue and systems level. Sexually distinct cardiovascular traits are conserved across mammalian species. Early developmental events are known to be important in influencing later adult characteristics, but how adult cardiovascular functions are ‘programmed’ differently for males and females is not understood. The project aims to uncover the importance of the placenta in regulating foetus exposure to sex steroids and the crucial effects of the pubertal hormone surge in shaping cardiovascular phenotypes of male and female offspring.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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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
How appetite-suppressing brain cells maintain normal function and prevent the development of obesity. The brain plays a critical role in body weight gain by balancing appetite-inducing and appetite-suppressing signals. An imbalance in this process causes obesity and promotes diabetes. The aim of this research is to identify how appetite-suppressing brain cells maintain normal function and prevent the development of obesity.
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.
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
Endogenous and environmental regulation of energy expenditure in skeletal muscle. Circadian and seasonal cycles impact on body weight; night shift workers have disrupted light-dark cycles and are predisposed to obesity. The project will investigate effects of both short and long term changes in day length on energy expenditure in skeletal muscle. Furthermore, the project will investigate mechanisms that control energy expenditure in muscle.
Novel anti-ageing peptides in the vascular system. The project will substantially improve basic understanding of the ageing process in blood vessels and provide scientific evidence to understand what preventative health care measures might work and why. It will also produce highly skilled and practically trained graduates, ready to contribute to the health industry.