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
Relaxin: molecular mechanisms of action in the reversal of fibrosis. Defects in relaxin and relaxin receptors are increasingly implicated as a cause of fibrosis which is associated with many disease processes. This study will examine the molecular mechanisms linking relaxin and fibrosis and will determine whether relaxin can be used to reverse the condition.
REGULATION OF RYANODINE RECEPTOR CALCIUM CHANNELS BY THE CALCIUM BINDING PROTEIN CALSEQUESTRIN. The project is to examine the functional interaction between two proteins in skeletal muscle that are essential for Ca2+ regulation and hence contraction, respiration and movement in all vertebrate species. One protein, the ryanodine receptor, releases calcium from stores inside the muscle cell. The other protein, calsequestrin, binds and sequesters calcium ions. We have recently discovered that th ....REGULATION OF RYANODINE RECEPTOR CALCIUM CHANNELS BY THE CALCIUM BINDING PROTEIN CALSEQUESTRIN. The project is to examine the functional interaction between two proteins in skeletal muscle that are essential for Ca2+ regulation and hence contraction, respiration and movement in all vertebrate species. One protein, the ryanodine receptor, releases calcium from stores inside the muscle cell. The other protein, calsequestrin, binds and sequesters calcium ions. We have recently discovered that the proteins also bind to each other and that calsequestrin regulates Ca2+ release from the stores through the ryanodine receptor ion channel. This regulation is likely to be important in conserving store calcium during stress or fatigue.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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0347278
Funder
Australian Research Council
Funding Amount
$383,000.00
Summary
Brain Slice Macroscopic Imaging and Electrophysiology Recording System. Electrical signals are the primary mode of communication between excitable cells, in particular, the cells (neurons) that comprise the brain and central nervous system. Understanding of the processes of cell-to-cell communication between neurons is of primary importance to our understanding of fundamental phenomena such as voluntary and reflex movement, sensory responses and learning and memory, as well as providing fundamen ....Brain Slice Macroscopic Imaging and Electrophysiology Recording System. Electrical signals are the primary mode of communication between excitable cells, in particular, the cells (neurons) that comprise the brain and central nervous system. Understanding of the processes of cell-to-cell communication between neurons is of primary importance to our understanding of fundamental phenomena such as voluntary and reflex movement, sensory responses and learning and memory, as well as providing fundamental knowledge of numerous disease states. We are applying for equipment to monitor electrical signals (both visually and electrically) of small groups of cells (neurons) or large groups of interconnected cells (macroscopic complexes) within the brain. Facilities of this type for the visual and electrical recording of cell communication and brain activity will be unique to these Universities in Australia and extremely rare in the scientific world.Read moreRead less
FERTILIZATION IN VIVO AND IN VITRO IN AUSTRALIAN MARSUPIALS. Using reproductive technology previously undeveloped in Australian marsupials this study addresses the most significant question still unresolved in marsupial reproductive biology - 'How does fertilization occur?' We propose to investigate the morphological and functional characteristics of fertilisation and its roles in early development in marsupials, the uniqueness of these events and their evolutionary significance. These findings ....FERTILIZATION IN VIVO AND IN VITRO IN AUSTRALIAN MARSUPIALS. Using reproductive technology previously undeveloped in Australian marsupials this study addresses the most significant question still unresolved in marsupial reproductive biology - 'How does fertilization occur?' We propose to investigate the morphological and functional characteristics of fertilisation and its roles in early development in marsupials, the uniqueness of these events and their evolutionary significance. These findings will not only further our knowledge of reproduction in marsupials and shed light on the evolutionary factors underlying sperm and egg design but will provide tools for assisted breeding programs for threatened wildlife and for the regulation of over abundant species.Read moreRead less
Signalling cross-talk through Suppressors Of Cytokine Signalling (SOCS) initiates luteolysis in the ovary. Members of the newly discovered SOCS protein family block cytokine signal transduction pathways, including those for prolactin and GH. We have discovered that one of these proteins, SOCS-3, is upregulated in the corpus luteum of the ovary by prostaglandins and propose that induction of prolactin or GH resistance is a hitherto unrecognised and critical step in luteolysis. We have also disco ....Signalling cross-talk through Suppressors Of Cytokine Signalling (SOCS) initiates luteolysis in the ovary. Members of the newly discovered SOCS protein family block cytokine signal transduction pathways, including those for prolactin and GH. We have discovered that one of these proteins, SOCS-3, is upregulated in the corpus luteum of the ovary by prostaglandins and propose that induction of prolactin or GH resistance is a hitherto unrecognised and critical step in luteolysis. We have also discovered that this cross-talk between prostaglandin- and cytokine-receptor signalling pathways occurs in preadipocyte and breast cell lines and propose that this research will serve as a paradigm for understanding how sensitivity to cytokines can be controlled at a molecular level.Read moreRead less
Natriuretic peptide hormones and the stress response of fish. There are two main benefits of our research to Australia. Firstly, the team that we have assembled have international reputations, and include scientists from overseas. This team will be led by Australian Institutions and will put Australian science in the forefront of a competitive field, internationally. Secondly, our research examines questions that are critical in our understanding of how animals respond to stressful events. T ....Natriuretic peptide hormones and the stress response of fish. There are two main benefits of our research to Australia. Firstly, the team that we have assembled have international reputations, and include scientists from overseas. This team will be led by Australian Institutions and will put Australian science in the forefront of a competitive field, internationally. Secondly, our research examines questions that are critical in our understanding of how animals respond to stressful events. The response to stress, if excessive, leads to ill-health in both humans and other animals. Our research examines new connections between stress and fish biology, which could lead to discoveries that are valuable in managing stress and health in wild and farmed fishes.Read moreRead less
Cross-bridge cycling-dependent activation of force production in the absence of Ca2+ in fast- and slow-twitch skeletal muscle fibre types. The project will contribute new knowledge about how skeletal muscle works, which will be published in top international journals in biological sciences. This will increase the reputation of Australian science in muscle research and will have the potential to benefit Australian people and Australian athletes. The project will also provide several Australian re ....Cross-bridge cycling-dependent activation of force production in the absence of Ca2+ in fast- and slow-twitch skeletal muscle fibre types. The project will contribute new knowledge about how skeletal muscle works, which will be published in top international journals in biological sciences. This will increase the reputation of Australian science in muscle research and will have the potential to benefit Australian people and Australian athletes. The project will also provide several Australian research students the opportunity to develop sophisticated laboratory and reasoning skills.Read moreRead less