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
Coping With Pressure: Respiratory Biology of Marine Mammals. Many marine mammals undergo severe, protracted lung collapse during deep dives. They also exhibit prolonged periods of apnea during sleep. In humans, lung collapse and sleep apnea both represent severe respiratory dysfunction. Pulmonary surfactant, a complex mixture that lines the lung, stabilises the lungs in terrestrial mammals, preventing lung collapse. Here, we propose a comprehensive examination of respiratory function in marine m ....Coping With Pressure: Respiratory Biology of Marine Mammals. Many marine mammals undergo severe, protracted lung collapse during deep dives. They also exhibit prolonged periods of apnea during sleep. In humans, lung collapse and sleep apnea both represent severe respiratory dysfunction. Pulmonary surfactant, a complex mixture that lines the lung, stabilises the lungs in terrestrial mammals, preventing lung collapse. Here, we propose a comprehensive examination of respiratory function in marine mammals. This study will significantly advance our knowledge of the diving physiology of Australian marine mammals. A detailed examination of the respiratory and surfactant systems of marine mammals may also reveal adaptations that enable these animals to endure sleep apnea and lung collapse.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
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
Dissecting the impact of stress on reproduction: Novel peptide mediates inhibitory effects of stress on female reproduction. This research proposal offers a pioneering opportunity to develop treatments that overcome the negative impact of stress on reproduction. Specifically, knowledge generated in this project will be vital in the development of strategic defences against the impact of stress on reproduction. This project fundamentally addresses Research Priority 2: Promoting and maintaining go ....Dissecting the impact of stress on reproduction: Novel peptide mediates inhibitory effects of stress on female reproduction. This research proposal offers a pioneering opportunity to develop treatments that overcome the negative impact of stress on reproduction. Specifically, knowledge generated in this project will be vital in the development of strategic defences against the impact of stress on reproduction. This project fundamentally addresses Research Priority 2: Promoting and maintaining good health. Given that suppression of reproduction by stress occurs in all mammalian species including humans, domestic animals and wildlife, being able to prevent or overcome stress-induced reproductive dysfunction will generate significant health, social, economic and ecological benefits. Read moreRead less
Investigating the evolution of innate and adaptive cellular immunity. This proposal aims to assess the impact of geographical and genetic isolation of the Australian Indigenous population on adaptive and innate immune systems. The project will use novel DNA sequencing approaches to generate the high resolution sequences of two genetic loci that regulate innate and adaptive immune responses, the major histocompatibility complex locus and the killer cell immunoglobulin-like receptor locus. In an i ....Investigating the evolution of innate and adaptive cellular immunity. This proposal aims to assess the impact of geographical and genetic isolation of the Australian Indigenous population on adaptive and innate immune systems. The project will use novel DNA sequencing approaches to generate the high resolution sequences of two genetic loci that regulate innate and adaptive immune responses, the major histocompatibility complex locus and the killer cell immunoglobulin-like receptor locus. In an initial screen, distinct variants and combinations of these genes were identified. This project aims to interrogate how variation in these critical genes impacts on the function of cytotoxic lymphocytes, providing insights into the evolutionary drivers of immune recognition mechanisms.Read moreRead less
Gas Phase Reactivity of Charged Peptide and DNA Radicals: Fundamentals and Applications. Radicals derived from the "molecules of life", proteins and DNA, play both beneficial (e.g. enzyme catalysis) and deleterious roles (e.g. protein and DNA damage associated with disease). Two electrospray ionisation mass spectrometry approaches have been discovered to generate charged radicals of related models systems (e.g. peptides and nucleobases). The gas phase chemistry of these species is a largely unch ....Gas Phase Reactivity of Charged Peptide and DNA Radicals: Fundamentals and Applications. Radicals derived from the "molecules of life", proteins and DNA, play both beneficial (e.g. enzyme catalysis) and deleterious roles (e.g. protein and DNA damage associated with disease). Two electrospray ionisation mass spectrometry approaches have been discovered to generate charged radicals of related models systems (e.g. peptides and nucleobases). The gas phase chemistry of these species is a largely unchartered area! We will examine the fundamental chemistry (unimolecular and bimolecular reactions) of these systems and build upon some exciting preliminary results which suggest potential applications (e.g. as a proteomics tool to sequence and distinguish between leucine and isoleucine residues in peptides).Read moreRead less
Structure and activity of host-defence peptides from Australian anurans: anticancer agents, neuropeptides and nNOS inhibitors. We have discovered peptides that may have clinical applications. This is significant as these molecules may have one or more of the following properties. They may have anti-cancer effects; they may increase the effectiveness of the immune system by enhancing lymphocyte formation; and, they may act to reduce inflammation, stroke or cardiac conditions by controlling nitri ....Structure and activity of host-defence peptides from Australian anurans: anticancer agents, neuropeptides and nNOS inhibitors. We have discovered peptides that may have clinical applications. This is significant as these molecules may have one or more of the following properties. They may have anti-cancer effects; they may increase the effectiveness of the immune system by enhancing lymphocyte formation; and, they may act to reduce inflammation, stroke or cardiac conditions by controlling nitric oxide formation. Another national benefit is that personnel involved in this project are trained to the highest international standards in peptide chemistry/mass spectrometry/nuclear magnetic resonance: currently, there are not enough trained scientists in this area to meet demand.Read moreRead less
Biologically active peptides and proteins from anurans: the relationship between structure and activity. We have identified peptides (from glands of frogs and toads), some of which are amongst the most powerful biologically active compounds in the animal kingdom. The aims of this project are to investigate the relationship between the structure and bioactivity of chosen groups of peptides including pheromones, anticancer and antibiotic peptides, and peptides which inhibit neuronal nitric oxide ....Biologically active peptides and proteins from anurans: the relationship between structure and activity. We have identified peptides (from glands of frogs and toads), some of which are amongst the most powerful biologically active compounds in the animal kingdom. The aims of this project are to investigate the relationship between the structure and bioactivity of chosen groups of peptides including pheromones, anticancer and antibiotic peptides, and peptides which inhibit neuronal nitric oxide synthase. It would be of national benefit if any of these peptides have applied application, e.g. if we can use the sex pheromone of the cane toad to reduce its population, or if we can produce an anticancer active peptide of clinical applicability.Read moreRead less
Tree-mediated methane fluxes: A new frontier in the global carbon cycle. Methane is an extremely potent greenhouse gas. Recent evidence suggests that tree-mediated fluxes may be a significant, but overlooked source of methane to the atmosphere. This project aims to quantify the magnitude and drivers of tree-mediated methane fluxes from Australia’s dominant forest types. Innovatively, we will be using a novel combination of empirical field based measurements, gas tracer experiments, microbial ana ....Tree-mediated methane fluxes: A new frontier in the global carbon cycle. Methane is an extremely potent greenhouse gas. Recent evidence suggests that tree-mediated fluxes may be a significant, but overlooked source of methane to the atmosphere. This project aims to quantify the magnitude and drivers of tree-mediated methane fluxes from Australia’s dominant forest types. Innovatively, we will be using a novel combination of empirical field based measurements, gas tracer experiments, microbial analysis and modelling methods. Expected outcomes are a mechanistic understanding of tree-mediated methane fluxes, helping to constrain regional, national and global methane budgets. The results of this study will help inform publicly funded greenhouse gas abatement strategies, ensuring a maximal return on investment.Read moreRead less