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.
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
Anti-ageing role for relaxin in blood vessels. Arteries stiffen with age. This is due to increased arterial smooth muscle tone and alterations in the extracellular matrix. In a sense, the artery undergoes ?fibrosis? with aging. In light of the anti-fibrotic attributes of the peptide hormone relaxin observed in other tissues, this collaborative project will investigate the potential role for relaxin in opposing arterial ?fibrosis? associated with aging. We will test the hypothesis that a reductio ....Anti-ageing role for relaxin in blood vessels. Arteries stiffen with age. This is due to increased arterial smooth muscle tone and alterations in the extracellular matrix. In a sense, the artery undergoes ?fibrosis? with aging. In light of the anti-fibrotic attributes of the peptide hormone relaxin observed in other tissues, this collaborative project will investigate the potential role for relaxin in opposing arterial ?fibrosis? associated with aging. We will test the hypothesis that a reduction in arterial relaxin expression in older animals is a major cause of arterial stiffening. Further studies will investigate the mechanisms by which relaxin administration can alleviate this phenomenon.Read moreRead less
Relaxin action in the heart, kidney, lung and uterus: understanding fibrosis. Relaxin is a peptide hormone associated with pregnancy. We have recently generated a relaxin gene knockout mouse and exciting preliminary data show that without relaxin, non-pregnant mice develop signs of fibrosis in the heart, lung and uterus. Combining our expertise in molecular biology, pharmacology and physiology, the overall objective of this project is to investigate the functions and mechanisms of relaxin action ....Relaxin action in the heart, kidney, lung and uterus: understanding fibrosis. Relaxin is a peptide hormone associated with pregnancy. We have recently generated a relaxin gene knockout mouse and exciting preliminary data show that without relaxin, non-pregnant mice develop signs of fibrosis in the heart, lung and uterus. Combining our expertise in molecular biology, pharmacology and physiology, the overall objective of this project is to investigate the functions and mechanisms of relaxin action in these organs. Our findings will provide important basic information on relaxin physiology and enable us to implement a long-term partnership with Connetics to understand how relaxin regulates collagen production and/or the development of fibrosis.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
Brain temperature regulation in mammals: mechanisms and consequences. Mammals detect increases in body temperature predominantly in the brain. Counterintuitively many mammals selectively cool the brain during heat stress, which appears to defeat the mechanism for inducing cooling responses. We intend to investigate this apparent anomaly which we believe is concerned with optimizing water use in hot conditions. We will further investigate the source of water for evaporative cooling by panting and ....Brain temperature regulation in mammals: mechanisms and consequences. Mammals detect increases in body temperature predominantly in the brain. Counterintuitively many mammals selectively cool the brain during heat stress, which appears to defeat the mechanism for inducing cooling responses. We intend to investigate this apparent anomaly which we believe is concerned with optimizing water use in hot conditions. We will further investigate the source of water for evaporative cooling by panting and discover if there has been convergent evolution in thermoregulatory strategies in the eutherian and marsupial lineages. The data we collect will be used to support a new model for thermoregulation in mammals.
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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
Epigenetic Regulation of Fetal and Placental Development. Perturbations of the environment of the early embryo can alter fetal and placental growth. The mechanisms by which the early environment alters development of the fetal adrenal-placental axis are unknown. This axis coordinates fetal growth and development to ensure a successful transition from intra- to extrauterine life. We propose a novel role for the epigenetic regulation of imprinted genes in the activation of the fetal adrenal and in ....Epigenetic Regulation of Fetal and Placental Development. Perturbations of the environment of the early embryo can alter fetal and placental growth. The mechanisms by which the early environment alters development of the fetal adrenal-placental axis are unknown. This axis coordinates fetal growth and development to ensure a successful transition from intra- to extrauterine life. We propose a novel role for the epigenetic regulation of imprinted genes in the activation of the fetal adrenal and in placental growth and differentiation. This proposal extends the 'genetic conflict' hypothesis of the role of imprinted genes beyond its current focus on the regulation of fetal nutrient supply and demand.Read moreRead less