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
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
Modulating the molecular and cellular physiology of ageing skeletal muscle. Understanding the underlying mechanisms of how ageing affects muscle is of increasing importance to the community as the number of older persons in the population continues to escalate and the age of retirement increases. Old muscles are slower and weaker than young muscles, and are more easily injured. This proposal is focussed on developing safe therapies to prevent or reverse these age-related effects. Making old musc ....Modulating the molecular and cellular physiology of ageing skeletal muscle. Understanding the underlying mechanisms of how ageing affects muscle is of increasing importance to the community as the number of older persons in the population continues to escalate and the age of retirement increases. Old muscles are slower and weaker than young muscles, and are more easily injured. This proposal is focussed on developing safe therapies to prevent or reverse these age-related effects. Making old muscles young again, is a research strategy that will promote healthy ageing and enable older Australians to enjoy a better quality of life.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
The Immunoregulatory Role of the Endogenous Cannabinoid Anandamide. Anandamides are naturally occurring fatty acids that act at the cannabinoid receptor expressed in the brain and periphery. A new proposal by our research group challenges traditional models of the disease process by suggesting that the anandamide system is an important imunoregulatory system that can be targeted by invading pathogens. We propose that disruption to the anandamide system, by bacteria or viruses acting at the rece ....The Immunoregulatory Role of the Endogenous Cannabinoid Anandamide. Anandamides are naturally occurring fatty acids that act at the cannabinoid receptor expressed in the brain and periphery. A new proposal by our research group challenges traditional models of the disease process by suggesting that the anandamide system is an important imunoregulatory system that can be targeted by invading pathogens. We propose that disruption to the anandamide system, by bacteria or viruses acting at the receptor to block immunological responses, contributes to chronic illness states. At this point we have good evidence that anandamides are immunoregulators, however, we have very little knowledge of their precise physiological role. The aim of this research is to begin to characterise the immunoregulatory role of the anandamide system. This project will provide a comprehensive understanding of this endogenous control system, the immunological properties of which have not previously been described. The outcome of this research may lead to the identification of new avenues for the development of pharmaceutical interventions that can target this system.Read moreRead less
The recirculation of myeloid dendritic cells. This project aims to understand dendritic cell recirculation. It will use virological tools to track dendritic cell migration, and identify key decision points. Expected outcomes include enhanced capacity in basic research and greater interdisciplinary collaboration between virology and immunology research groups. Significant benefits will include a new understanding of how G protein coupled receptor signalling and other tissue cues guide dendritic c ....The recirculation of myeloid dendritic cells. This project aims to understand dendritic cell recirculation. It will use virological tools to track dendritic cell migration, and identify key decision points. Expected outcomes include enhanced capacity in basic research and greater interdisciplinary collaboration between virology and immunology research groups. Significant benefits will include a new understanding of how G protein coupled receptor signalling and other tissue cues guide dendritic cell recirculation, and what consequences the recirculation has for immune cell function. This understanding will significantly advance our basic understanding of the immune system.Read moreRead less
Calls and constraints: do male frogs signal direct benefits? There is international concern over recent declines and disappearances of many species of amphibians. Australia is a hotspot for declines, but causes of declines remain enigmatic. Approximately one quarter of Australia's 230 amphibian species breed in terrestrial situations, but processes such as salinity, wetland and urban developments and climate change are altering the hydrology of our landscape, and preventing the flood events nece ....Calls and constraints: do male frogs signal direct benefits? There is international concern over recent declines and disappearances of many species of amphibians. Australia is a hotspot for declines, but causes of declines remain enigmatic. Approximately one quarter of Australia's 230 amphibian species breed in terrestrial situations, but processes such as salinity, wetland and urban developments and climate change are altering the hydrology of our landscape, and preventing the flood events necessary for the completion of the lifecycle of many species. This research has important conservation implications because it examines the effects of variable moisture regimes on the physiology and reproductive behaviours of terrestrial breeding frogs.Read moreRead less