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
Aquaporin channels in cell migration. The project aims to determine the role of Aquaporin1 (AQP1) in enhancing rapid cell motility. Cell migration is important for development, repair, and protection in multicellular organisms. AQP1 is increased in some rapidly migrating cell types. Loss of AQP1 impairs migration, which is restored by reintroduction of AQP1 but not AQP4. Expected outcomes include defining the features of AQP1 that confer enhanced cell migration. The project will test the hypothe ....Aquaporin channels in cell migration. The project aims to determine the role of Aquaporin1 (AQP1) in enhancing rapid cell motility. Cell migration is important for development, repair, and protection in multicellular organisms. AQP1 is increased in some rapidly migrating cell types. Loss of AQP1 impairs migration, which is restored by reintroduction of AQP1 but not AQP4. Expected outcomes include defining the features of AQP1 that confer enhanced cell migration. The project will test the hypothesis that dual water and ion channel functions of AQP1 are needed for movement, using migration assays in cells with wild type and mutant AQP1, and selective pharmacological agents developed by the project team to dissect the essential channel properties that enable rapid migration in cancer and stem cells. The project seeks to build knowledge of AQP roles in development, regeneration and surveillance, potentially improving health care by revealing pathways in migration disorders such as metastasis.Read moreRead less
Fundamental roles of aquaporin-1 channels in cell migration and morphology. This project aims to investigate cell migration mechanisms and the roles of aquaporin channels in controlling cell motility and morphology. The ability of cells to move and maintain proper shape is important for development, repair and survival in multicellular organisms. This project will test the role of mammalian aquaporin-1 channels in enabling rapid migration in normal and cancer cells, in repairing barrier layers i ....Fundamental roles of aquaporin-1 channels in cell migration and morphology. This project aims to investigate cell migration mechanisms and the roles of aquaporin channels in controlling cell motility and morphology. The ability of cells to move and maintain proper shape is important for development, repair and survival in multicellular organisms. This project will test the role of mammalian aquaporin-1 channels in enabling rapid migration in normal and cancer cells, in repairing barrier layers in kidney and brain, and in allowing red blood cells to maintain the classic disk-shape needed for optimal transport. Outcomes will define features of aquaporin-1 that provide these functions, using molecular, optical and pharmacological tools. Results will define aquaporin channel properties that enable optimal cellular function.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
Huntingtin-associated protein 1 controls cell communication. The purpose of this study is to identify the mechanisms by which a novel regulator of cell communication which we have identified is able to control the release of chemical signals from a cell. This project will provide critical insight into a cellular pathway that underlies hormone secretion, neurotransmission and higher brain functions.
Environmental control of genetic/phenotypic interactions in lung development: An evolutionary perspective. Vertebrate lungs all contain morphologically and functionally similar lung lining cells. However, the cellular arrangement (i.e. lung morphology) and the function of the surfactant these cells produce, differs dramatically between species. Hence, a subset of highly conserved lung-specific genes coincides with spectacular phenotypic diversity. How has this diversity evolved? Do environmental ....Environmental control of genetic/phenotypic interactions in lung development: An evolutionary perspective. Vertebrate lungs all contain morphologically and functionally similar lung lining cells. However, the cellular arrangement (i.e. lung morphology) and the function of the surfactant these cells produce, differs dramatically between species. Hence, a subset of highly conserved lung-specific genes coincides with spectacular phenotypic diversity. How has this diversity evolved? Do environmental conditions, birth strategy or phylogenetic relationships determine lung phenotype? We will experimentally manipulate developing lungs and cells to demonstrate how environmental conditions (temperature, oxygen, lung-fluid regulation and neuro-hormonal input) promote evolutionary processes by altering gene expression, protein/lipid synthesis, cellular differentiation and hence lung morphology/function in animals with different birth strategies.Read moreRead less
Matching of gas exchanger structure and function with activity and environment in air-breathing fishes. This project will investigate the physiology and structure of Australian fishes that use gills and breathe air. It will measure the partitioning of oxygen and carbon dioxide exchange between the aquatic (gills) and aerial (lung, swim-bladder or mouth) respiratory organs, in relation to dissolved oxygen in the water and metabolic energy demands by the fish. Rates of gas exchange, biochemical ....Matching of gas exchanger structure and function with activity and environment in air-breathing fishes. This project will investigate the physiology and structure of Australian fishes that use gills and breathe air. It will measure the partitioning of oxygen and carbon dioxide exchange between the aquatic (gills) and aerial (lung, swim-bladder or mouth) respiratory organs, in relation to dissolved oxygen in the water and metabolic energy demands by the fish. Rates of gas exchange, biochemical characteristics of the blood, anatomy and physiology of the exchange organs, and respiratory/locomotory coupling will be measured in three selected species during graded exercise. The results will help us understand the factors influencing the evolution of air-breathing.Read moreRead less
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