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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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.
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
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
Understanding the determinants of age-related muscle wasting in females . This project aims to investigate the fundamental mechanisms underlying age-related muscle wasting in females. Females live longer than males and are more susceptible to the consequences of muscle ageing. Yet, our current knowledge is overwhelmingly inferred from findings from male cohorts. By comprehensively mapping the functional, molecular and epigenetic mechanisms of ageing in female muscle, this project will generate n ....Understanding the determinants of age-related muscle wasting in females . This project aims to investigate the fundamental mechanisms underlying age-related muscle wasting in females. Females live longer than males and are more susceptible to the consequences of muscle ageing. Yet, our current knowledge is overwhelmingly inferred from findings from male cohorts. By comprehensively mapping the functional, molecular and epigenetic mechanisms of ageing in female muscle, this project will generate new, fundamental knowledge that will allow a unique interpretation of previous research through a sex-specific lens. This knowledge will contribute to better inform sex-specific models of research and practice in the future, ultimately delivering economic and social benefits for Australia and international communities.Read moreRead less
Muscle fibre excitability and calcium regulation in skeletal muscle of amphibians and mammals. The fundamental role of skeletal muscle is posture and movement. Essential for this is a specialised cell structure and a complex regulation of function. This project will define key aspects of muscle structure and functional regulation crucial to developing targets for improving function under stressed states such as fatigue, disease and age.
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
Discovery Early Career Researcher Award - Grant ID: DE150100538
Funder
Australian Research Council
Funding Amount
$342,000.00
Summary
Understanding the role of miRNAs in the biology of ageing muscle. Skeletal muscle is the largest organ in the body and plays a vital role in maintaining independent living and social interaction. As it ages, skeletal muscle loses its ability to build up new muscle proteins. However, the principles underlying the biology of skeletal muscle ageing are not well understood. MicroRNAs (MiRNAs) are essential regulators of skeletal muscle biology. Whether they play a role in the ageing process and how ....Understanding the role of miRNAs in the biology of ageing muscle. Skeletal muscle is the largest organ in the body and plays a vital role in maintaining independent living and social interaction. As it ages, skeletal muscle loses its ability to build up new muscle proteins. However, the principles underlying the biology of skeletal muscle ageing are not well understood. MicroRNAs (MiRNAs) are essential regulators of skeletal muscle biology. Whether they play a role in the ageing process and how they regulate muscle protein synthesis as we age has not been investigated. This project aims to identify the MiRNA species involved in muscle protein synthesis and will provide a better understanding of the biology of ageing skeletal muscle.Read moreRead less