Investigation of the fundamental roles of class Ib MHC (major histocompatibility complex) molecules in immunity. The proposed research program, using laboratory-based and synchrotron-based radiation, will provide insight into the roles of a poorly understood class of immune molecules. This will improve our understanding of the regulation of immunity, and the knowledge gained will increase Australia's international research profile.
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
Cell death by self-eating: Autophagy-dependent tissue removal. This project aims to study the mechanisms and regulation of autophagy-dependent cell death. Cell death maintains cell and tissue homeostasis. Although most cell death is mediated by apoptosis, other modes of cell deletion have emerged recently. One form of cell death involves autophagy, the catabolic process of cellular self-digestion through lysosomal enzymes. As autophagy is a default mechanism of cell survival under stress, the id ....Cell death by self-eating: Autophagy-dependent tissue removal. This project aims to study the mechanisms and regulation of autophagy-dependent cell death. Cell death maintains cell and tissue homeostasis. Although most cell death is mediated by apoptosis, other modes of cell deletion have emerged recently. One form of cell death involves autophagy, the catabolic process of cellular self-digestion through lysosomal enzymes. As autophagy is a default mechanism of cell survival under stress, the idea of autophagy-dependent cell death has been controversial. This proposal aims to resolve this question and provide highly topical knowledge of broad biological significance.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
Symbiotic transport proteins in legumes. Some plants form a symbiosis with soil bacteria (rhizobia) that convert atmospheric nitrogen to ammonia which is then supplied to the plant. This enables legumes to grow without application of nitrogen-based fertilizer, avoiding environmental problems such as run-off and land degradation, thereby contributing to sustainable agriculture practise. We will investigate the interactions between plant and rhizobia, focusing on identifying genes and proteins wh ....Symbiotic transport proteins in legumes. Some plants form a symbiosis with soil bacteria (rhizobia) that convert atmospheric nitrogen to ammonia which is then supplied to the plant. This enables legumes to grow without application of nitrogen-based fertilizer, avoiding environmental problems such as run-off and land degradation, thereby contributing to sustainable agriculture practise. We will investigate the interactions between plant and rhizobia, focusing on identifying genes and proteins which govern nutrient exchange between the partners and development of the special structures in the roots that house the bacteria. Subsequent manipulation of these genes and proteins may allow us to identify control points and enhance nitrogen fixation.
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The role of the ammonium transport bHLHm1/AMF1 regulatory loci in plants. This project aims to investigate the role of a regulatory locus in the regulation of ammonium transport in plants and the interacting genetic and biochemical signalling promoting the interaction. Ammonium is an important nutrient source for plant growth and development. It has been recently identified that a new transport mechanism (AMF1 ) mediates ammonium transport across legume root nodule cellular membranes. AMF1 was i ....The role of the ammonium transport bHLHm1/AMF1 regulatory loci in plants. This project aims to investigate the role of a regulatory locus in the regulation of ammonium transport in plants and the interacting genetic and biochemical signalling promoting the interaction. Ammonium is an important nutrient source for plant growth and development. It has been recently identified that a new transport mechanism (AMF1 ) mediates ammonium transport across legume root nodule cellular membranes. AMF1 was identified through a transcriptional interaction with a membrane localised bHLHm1 transcription factor. Both bHLHm1 and AMF1 belong to a unique chromosomal regulatory locus common across sequenced dicot plant species.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.
Transcription factor nuclear residency as a driver of gene expression. Persistently active proteins can stay in the nucleus to drive cell growth and prevent cell death. This project will define how one specific active protein can remain in the nucleus and regulate gene expression through the action of unique ribonucleic acid (RNA) molecules. The results will enable persistent gene activation to be manipulated in cancer.
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