Understanding the neuronal mechanisms underlying inherited epilepsies. Epilepsy is a serious disease that impacts severely on individuals and the community as a whole. Conservative estimates suggest a financial cost of more than $2 billion per annum. Drug treatment for this disease is often not adequate. Recent advances have allowed scientists to determine mutation in human genes that cause epilepsy. New models of epilepsy based on this knowledge will allow us to better understand what causes e ....Understanding the neuronal mechanisms underlying inherited epilepsies. Epilepsy is a serious disease that impacts severely on individuals and the community as a whole. Conservative estimates suggest a financial cost of more than $2 billion per annum. Drug treatment for this disease is often not adequate. Recent advances have allowed scientists to determine mutation in human genes that cause epilepsy. New models of epilepsy based on this knowledge will allow us to better understand what causes epilepsy enabling us to devise new and potent therapeutic strategies to treat the disease.Read moreRead less
The macrophage nucleus - its form and function during migration in vivo. As cells migrate through tissues, they encounter complex, 3-dimensional environments that provide cues to guide them and present obstacles in their path. This project focuses on macrophages, a large immune cell capable of both amoeboid and mesenchymal modes of migration. The nucleus is the largest organelle and its bulk and stiffness must be managed as migrating cells travel through constrictions. The project uses specialis ....The macrophage nucleus - its form and function during migration in vivo. As cells migrate through tissues, they encounter complex, 3-dimensional environments that provide cues to guide them and present obstacles in their path. This project focuses on macrophages, a large immune cell capable of both amoeboid and mesenchymal modes of migration. The nucleus is the largest organelle and its bulk and stiffness must be managed as migrating cells travel through constrictions. The project uses specialised high-end microscopy and genetic methods to examine how the nucleus of migrating zebrafish macrophages deforms, repositions and is restructured during migration in living tissues, and how this influences macrophage locomotion. The goal is to provide fundamental insights into the cell biology of macrophage migration.Read moreRead less
Transduction of neuronal signals by brain macroglial cells: implications for neuronal function. Study of mechanisms regulating brain cell (neuron and glial) communication is essential for understanding of normal brain function and transformations that occur in neurodegenerative states and age-related disorders. Mechanisms underlying neuron-glia communication are not well understood. By combining cell physiology, digital imaging technologies, and genetically designed and delivered molecules we w ....Transduction of neuronal signals by brain macroglial cells: implications for neuronal function. Study of mechanisms regulating brain cell (neuron and glial) communication is essential for understanding of normal brain function and transformations that occur in neurodegenerative states and age-related disorders. Mechanisms underlying neuron-glia communication are not well understood. By combining cell physiology, digital imaging technologies, and genetically designed and delivered molecules we will enhance our understanding of this brain cell communication and critical roles played by intracellular calcium. This will enhance international competitiveness of Australian biological research and provide novel insight of glial function in neurodegeneration and potential for specific therapeutic intervention in disease.Read moreRead less
Regulation of local lymphocyte trafficking and its role during infection. The study of early immune responses will contribute to the development of better vaccination strategies. In particular it will contribute by helping to understand the essential differences between reactogenicity and immunogenicity and how this relates to adjuvants. Using this understanding it will be possible to develop novel adjuvants that induce appropriate immunity with minimal side effects.
Development of novel vaccine delivery systems for induction of mucosal immunity in a large animal model. The induction of mucosal immune responses is a highly desirable goal in vaccine research and development, as it prevents entry of the large number of mucosal pathogens. This proposal aims to develop new mucosal vaccine delivery systems by combining intra-nasal, intra-lung and transcutaneous vaccine delivery with ISCOM-based adjuvants. The nature of the immune response will be analysed in real ....Development of novel vaccine delivery systems for induction of mucosal immunity in a large animal model. The induction of mucosal immune responses is a highly desirable goal in vaccine research and development, as it prevents entry of the large number of mucosal pathogens. This proposal aims to develop new mucosal vaccine delivery systems by combining intra-nasal, intra-lung and transcutaneous vaccine delivery with ISCOM-based adjuvants. The nature of the immune response will be analysed in real time using a sheep cannulation model. Subsequently, the efficacy of mucosal vaccination strategies will be tested in a chlamydia infection model.Read moreRead less
Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will ....Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will be a thorough characterisation of a novel regulatory paradigm in neurons that is likely to be crucial for neuronal development and regeneration, and will potentially provide novel therapeutic targets for various neuronal diseases.Read moreRead less
Assembly and function of arabinogalactan-proteins: a class of proteoglycans involved in plant growth and development. We aim to define the mechanisms by which a family of cell surface proteoglycans, the arabinogalactan-proteins (AGPs), are assembled and contribute to the regulation of plant growth and development using Arabidopsis, a model system amenable to a functional genomics strategy. This will be achieved through the application of bioinformatics for gene discovery and molecular, biochemi ....Assembly and function of arabinogalactan-proteins: a class of proteoglycans involved in plant growth and development. We aim to define the mechanisms by which a family of cell surface proteoglycans, the arabinogalactan-proteins (AGPs), are assembled and contribute to the regulation of plant growth and development using Arabidopsis, a model system amenable to a functional genomics strategy. This will be achieved through the application of bioinformatics for gene discovery and molecular, biochemical and genetics approaches to define gene function. Understanding mechanisms that control plant growth and development will ultimately impact on industries (agriculture, horticulture and forestry) vital to Australia's prosperity.Read moreRead less
Assembly and function of arabinogalactan-proteins: a class of proteoglycans involved in plant growth and development. Achievements of the Objectives will specifically address National Research Priority 3 by developing breakthrough science and utilising frontier technologies with application to Australia's agri-biotechnology industries. In addition to contributing to world class research outcomes, we will train highly skilled graduates and postdoctoral fellows in functional genomics technologies, ....Assembly and function of arabinogalactan-proteins: a class of proteoglycans involved in plant growth and development. Achievements of the Objectives will specifically address National Research Priority 3 by developing breakthrough science and utilising frontier technologies with application to Australia's agri-biotechnology industries. In addition to contributing to world class research outcomes, we will train highly skilled graduates and postdoctoral fellows in functional genomics technologies, thereby contributing to the "knowledge nation".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