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
Characterisation of bone and bone marrow resident tissue macrophages. This project aims to elucidate the identities of tissue macrophages involved in bone and blood system (bone marrow) homeostasis and function, and the molecular signatures underpinning their functional specialisation. It will then investigate whether decline in the function of these specialised macrophages occurs during skeletal and blood system ageing. Both skeletal and blood system decline contribute to age-associated loss of ....Characterisation of bone and bone marrow resident tissue macrophages. This project aims to elucidate the identities of tissue macrophages involved in bone and blood system (bone marrow) homeostasis and function, and the molecular signatures underpinning their functional specialisation. It will then investigate whether decline in the function of these specialised macrophages occurs during skeletal and blood system ageing. Both skeletal and blood system decline contribute to age-associated loss of productivity, and paralleled decline in the resident macrophages in these organs may be a common ageing mechanism. Demonstration that altered macrophage biology unpins decline in blood and bone may prolong peak health and increase productivity in the ageing population.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.
Read moreRead less
The comparative physiology of oxygen delivery to the kidney. The kidney is in danger of hyperoxia because the kidney receives so much blood relative to its mass. It is proposed that shunting oxygen between arteries and veins substantially mitigates the risk of hyperoxia, but under certain circumstances shunting substantially increases the risk of kidney hypoxia. Using a combination of synchrotron and histological imaging, This project will carefully define the three-dimensional vasculature of th ....The comparative physiology of oxygen delivery to the kidney. The kidney is in danger of hyperoxia because the kidney receives so much blood relative to its mass. It is proposed that shunting oxygen between arteries and veins substantially mitigates the risk of hyperoxia, but under certain circumstances shunting substantially increases the risk of kidney hypoxia. Using a combination of synchrotron and histological imaging, This project will carefully define the three-dimensional vasculature of the renal cortex in several different species and interpret its functional significance using computational modeling. The outcome of this project will be a new understanding in the comparative physiology of oxygen transport and shunting in the kidney.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