Regulatory mechanisms for calcium release-activated calcium channels. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, growth factors and other physiological stimuli. The aims of this project are to elucidate the mechanisms that regulate the activity of store-operated channels and how their properties can be modulated by different pharmacological agents. Using chiefly the techniques of ele ....Regulatory mechanisms for calcium release-activated calcium channels. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, growth factors and other physiological stimuli. The aims of this project are to elucidate the mechanisms that regulate the activity of store-operated channels and how their properties can be modulated by different pharmacological agents. Using chiefly the techniques of electrophysiology and molecular biology we expect to learn the fundamental mechanisms that modulate the opening and closing of store-operated calcium channels and to gain an important information that can be used for determining the molecular structure of these channelsRead moreRead less
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
Gating and permeation in ClC channels. Chloride ion channels are essential proteins in all living cells but, compared to other channels, little is known of their structure or how this defines and controls chloride transport. We will produce both normal and structurally modified (mutant and known to cause disease) chloride channels in cultured cells by genetic engineering so that we can analyse channel function using a combination of electrophysiological and chemical methods. We expect to learn ....Gating and permeation in ClC channels. Chloride ion channels are essential proteins in all living cells but, compared to other channels, little is known of their structure or how this defines and controls chloride transport. We will produce both normal and structurally modified (mutant and known to cause disease) chloride channels in cultured cells by genetic engineering so that we can analyse channel function using a combination of electrophysiological and chemical methods. We expect to learn which channel parts are fundamental and how subtle changes in structure can alter the opening and closing of these channels and the way that chloride passes through them.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
Activation mechanisms of store-operated calcium channels in liver cells. Currently, one of the most active areas of research in biology involves the molecular mechanisms that control the activity of cells. Defining these will provide a deeper understanding of normal function and disease, and provide potential therapeutic targets. This group has an international reputation for its work and it makes a major input to maintaining Australia as a significant contributor to this field. While its resea ....Activation mechanisms of store-operated calcium channels in liver cells. Currently, one of the most active areas of research in biology involves the molecular mechanisms that control the activity of cells. Defining these will provide a deeper understanding of normal function and disease, and provide potential therapeutic targets. This group has an international reputation for its work and it makes a major input to maintaining Australia as a significant contributor to this field. While its research has broad application in biology, its specific focus, calcium signalling in the liver, will provide the basis for understanding liver function and disease and, potentially, for developing new treatments for liver disease associated with abnormal calcium homeostasis.Read moreRead less
Structural and functional characterisation of PI3Kgamma, uniquely activated by p101. The movement of cells is involved in all aspects of life including development, growth and maintenance of organisms. In spite of this, our understanding of the mechanism involved in cell migration is limited. There are a number of conditions in which the ability to control cell movement would be of significant benefit. Examples include autoimmune conditions, asthma and cancer, the social and economic burdens ....Structural and functional characterisation of PI3Kgamma, uniquely activated by p101. The movement of cells is involved in all aspects of life including development, growth and maintenance of organisms. In spite of this, our understanding of the mechanism involved in cell migration is limited. There are a number of conditions in which the ability to control cell movement would be of significant benefit. Examples include autoimmune conditions, asthma and cancer, the social and economic burdens of which account for billions of dollars and millions of Australians. This project aims to understand one of the major mechanisms that controls cell migration, which is expected to produce significant economic and social outcomes in the areas of basic science knowledge, human health, and biotechnology. Read moreRead less
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
Development Of An Artificial Vision System For Motion Detection. This work will have a broader impact beyond the advancement of a particular area of neurophysiology since it aims to produce a simple, robust velocity estimator in computer models and subsequently in silicon chips. We have already demonstrated the feasibility of transferring our basic preliminary models onto VLSI chips. Consistent with National Research Priorities 3 (Frontier Technologies), 4 (Defence Technologies) & 2 (Promoting a ....Development Of An Artificial Vision System For Motion Detection. This work will have a broader impact beyond the advancement of a particular area of neurophysiology since it aims to produce a simple, robust velocity estimator in computer models and subsequently in silicon chips. We have already demonstrated the feasibility of transferring our basic preliminary models onto VLSI chips. Consistent with National Research Priorities 3 (Frontier Technologies), 4 (Defence Technologies) & 2 (Promoting and Maintaining Good Health) our work has applications in the area of miniature autonomous systems in defence and civilian roles, including miniature unmanned aerial vehicles and collision avoidance detectors, while in the longer term it will serve as the basis for designing implantable artificial eyes.Read moreRead less