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
Male to female sperm signalling – a new role for sperm in reproduction? Male seminal fluid is commonly thought simply to provide sperm for conception. This project aims to investigate a lesser known action of sperm: modifying the female immune response to increase the chances of reproductive success. The project aims to define the molecular pathway through which sperm interact with female cells, particularly how B-defensins on sperm bind to Toll-like receptors to stimulate female immune toleranc ....Male to female sperm signalling – a new role for sperm in reproduction? Male seminal fluid is commonly thought simply to provide sperm for conception. This project aims to investigate a lesser known action of sperm: modifying the female immune response to increase the chances of reproductive success. The project aims to define the molecular pathway through which sperm interact with female cells, particularly how B-defensins on sperm bind to Toll-like receptors to stimulate female immune tolerance. The project plans to use embryo transfer and genetic mouse models to determine the physiological benefit of sperm signalling. Evidence that seminal fluid signalling operates in mammals to ensure optimal female reproductive investment would advance knowledge of the male contribution to the reproductive process.Read moreRead less
Interactions between cells and extracellular matrix in the epithelial-mesenchymal transition of the ovarian follicular stratified epithelium. The lining of many mammalian organs and cavities contain cells that can transform into different cells to bring about organ development or repair but if it goes horribly wrong the cells become metastatic cancers. This project examines the key features of this process especially the roles of matrix that develops around the cells in this process.
Seminal fluid interferon-gamma: a potential inhibitor of reproductive success. This project aims to investigate mechanisms by which infection, heat stress and psycho-social stress interfere with fertility by inducing a signalling factor in seminal fluid that suppresses female immune adaptation for pregnancy. Factors in seminal fluid in addition to sperm parameters are known to affect male reproductive success, but these are not well defined. The cytokine interferon-gamma (IFNG) is variably prese ....Seminal fluid interferon-gamma: a potential inhibitor of reproductive success. This project aims to investigate mechanisms by which infection, heat stress and psycho-social stress interfere with fertility by inducing a signalling factor in seminal fluid that suppresses female immune adaptation for pregnancy. Factors in seminal fluid in addition to sperm parameters are known to affect male reproductive success, but these are not well defined. The cytokine interferon-gamma (IFNG) is variably present in seminal plasma of several mammalian species. It was recently discovered that IFNG interferes with the female immune response required for reproductive success. This project will investigate how seminal fluid IFNG alters female immune adaptation for pregnancy. This will define how environmental factors induce seminal fluid IFNG and determine whether inhibitory effects of IFNG can be overcome with pharmacological inhibitors to boost reproductive success.Read moreRead less
Mechanistic basis of a reproductive lesion in transforming growth factor beta-1 (TGFb1) null mutant mice. Null mutation in the gene encoding the cytokine transforming growth factor beta-1 (TGFb1) causes infertility in male and female mice. In recent experiments we have found that TGFb1 deficiency is associated with impaired ovarian and testicular steroidogenesis, arrested development of pre-implantation embryos and disrupted mammary gland morphogenesis. The aims of the current project are to un ....Mechanistic basis of a reproductive lesion in transforming growth factor beta-1 (TGFb1) null mutant mice. Null mutation in the gene encoding the cytokine transforming growth factor beta-1 (TGFb1) causes infertility in male and female mice. In recent experiments we have found that TGFb1 deficiency is associated with impaired ovarian and testicular steroidogenesis, arrested development of pre-implantation embryos and disrupted mammary gland morphogenesis. The aims of the current project are to unravel the mechanistic basis of the reproductive lesion in TGFb1 null mutant mice and to determine the effect of exogenous systemic delivery of TGFb1 in alleviating this lesion. It is expected that the project will provide new insight into key roles for TGFb1 in governing male and female fertility, and shed light on the prospects for exogenous supplementation of TGFb1 for improving reproductive performance in wild-type animals. This knowledge has potentially important applications in the livestock breeding industry, in devising novel contraceptive vaccine strategies, in the human pharmaceutical industry, and in devising novel contraceptive vaccine strategies.Read moreRead less
Environmental Control of Developmental Plasticity of Vertebrate Cardio-Pulmonary Systems. Our research will generate the first comprehensive picture of how environmental conditions are transduced to control the development of the vertebrate respiratory and cardiovascular systems over the perinatal period. The research will demonstrate how physiological systems are modified and hence evolve. Moreover, understanding the developmental pathology in embryos induced by changing environmental condition ....Environmental Control of Developmental Plasticity of Vertebrate Cardio-Pulmonary Systems. Our research will generate the first comprehensive picture of how environmental conditions are transduced to control the development of the vertebrate respiratory and cardiovascular systems over the perinatal period. The research will demonstrate how physiological systems are modified and hence evolve. Moreover, understanding the developmental pathology in embryos induced by changing environmental conditions (especially exposure to steroid-like pollutants) is crucial to support breeding programs of endangered species and may improve veterinary and medicinal treatment of premature animals and humans. This multi-disciplinary, international collaboration provides an international training ground and two-way exchange of students and postdocs.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
Unravelling the principles of bilateral brain wiring. This project seeks to investigate the molecular principles of brain wiring in mammals and how small changes can generate complex outcomes. Neurons in the mammalian brain must be precisely wired together for the brain to function correctly. The project aims to identify the molecular and cellular rules governing commissural wiring in the mammalian cortex to determine how the largest fibre tract in the human brain, the corpus callosum, evolved. ....Unravelling the principles of bilateral brain wiring. This project seeks to investigate the molecular principles of brain wiring in mammals and how small changes can generate complex outcomes. Neurons in the mammalian brain must be precisely wired together for the brain to function correctly. The project aims to identify the molecular and cellular rules governing commissural wiring in the mammalian cortex to determine how the largest fibre tract in the human brain, the corpus callosum, evolved. This may have involved modifications in mechanisms affecting axon guidance that differ between placentals and marsupials. The project investigates the regulatory gene networks determining commissural neuron fate, the regulation of axon guidance components, and the influence of surrounding brain tissue on the development of commissural connections.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
The developmental genetics of major evolutionary transitions: a multidisciplinary investigation of limb reduction and loss in lizards. The five-toed limb is an iconic evolutionary innovation of land vertebrates, yet has been lost repeatedly. This project will use anatomical, developmental and genetic approaches to understand how vertebrates lose their legs, whether limbs can be reacquired, and the degeneration of limb genes after they lose their function (analogous to 'vestigial organs').