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
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
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
HEN1 is a regulator of piRNA metabolism, transcriptional regulation and mammalian male fertility. This project is to define the biochemistry of a previously uncharacterized protein in male fertility using a unique mouse model and innovative DNA and protein technologies. This project will define a novel, and essential, pathway for male fertility and may ultimately have relevance to the maintenance of health or improving fertility.
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
Genetic control of spermatogenesis: defining the role of SOX3 in spermatogonial progenitor cells. The transcription factor (TF) SOX3 is a key regulator of neural stem/progenitor cells. Recently, this project has also shown that SOX3 is active in sperm progenitors (spermatogonia) and is required for spermatogenesis. Using our Sox3 KO mouse model and extensive expertise in spermatogonial cell culture, ChIP-seq technology and bioinformatics, this project will investigate crucial aspects of SOX3 fun ....Genetic control of spermatogenesis: defining the role of SOX3 in spermatogonial progenitor cells. The transcription factor (TF) SOX3 is a key regulator of neural stem/progenitor cells. Recently, this project has also shown that SOX3 is active in sperm progenitors (spermatogonia) and is required for spermatogenesis. Using our Sox3 KO mouse model and extensive expertise in spermatogonial cell culture, ChIP-seq technology and bioinformatics, this project will investigate crucial aspects of SOX3 function in the testes including stem versus progenitor cell activity and genome-wide target gene regulation. These studies will uncover the molecular and cellular mechanism by which SOX3 controls spermatogenesis and provide unique insight into how a single TF controls context-dependent differentiation in sperm versus brain progenitor cells.Read moreRead less
Immunisation to protect against transmissible cancers in Tasmanian devils. This project aims to identify the immune escape mechanisms that the transmissible cancers, Devil Facial Tumour Disease (DFTD) use to avoid being killed by the immune system. Since the discovery of the second transmissible cancer (DFT2) mystery surrounds whether the devils immune system can respond to this cancer, hence this project will investigate the immune response to DFT2. The final aims are to develop a vaccine with ....Immunisation to protect against transmissible cancers in Tasmanian devils. This project aims to identify the immune escape mechanisms that the transmissible cancers, Devil Facial Tumour Disease (DFTD) use to avoid being killed by the immune system. Since the discovery of the second transmissible cancer (DFT2) mystery surrounds whether the devils immune system can respond to this cancer, hence this project will investigate the immune response to DFT2. The final aims are to develop a vaccine with the potential to protect healthy devils and cure devils with DFTD.Read moreRead less
Evolution of the unique fauna of the Great Artesian Basin mound springs: the impact of aridification and climate change. The mound springs of the Great Artesian Basin represent one of Australia's most unique environments and are of national biodiversity, cultural and economic significance. Their conservation is a major issue following listing of the springs as a threatened ecological community. As economic productivity in the GAB intensifies, the mound springs are under increasing threat from es ....Evolution of the unique fauna of the Great Artesian Basin mound springs: the impact of aridification and climate change. The mound springs of the Great Artesian Basin represent one of Australia's most unique environments and are of national biodiversity, cultural and economic significance. Their conservation is a major issue following listing of the springs as a threatened ecological community. As economic productivity in the GAB intensifies, the mound springs are under increasing threat from escalating groundwater use. The results of this study on the evolution of two crustacean groups will provide significant biological information for management plans, facilitating conservation of mound springs communities, and helping to understand the impacts of water extraction and climate change on this unique habitat.Read moreRead less