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
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
G-protein coupled receptor-mediated calcium signalling in parasympathetic neurons. External chemical stimuli act on specific cell-surface receptors of neurons resulting in an increase in the intracellular calcium ion concentration which acts as a second messenger to alter neuronal excitability. There are, however, many receptors acting through a number of closely related proteins involving complex intracellular signalling pathways which remain poorly understood. This project uses molecular, elec ....G-protein coupled receptor-mediated calcium signalling in parasympathetic neurons. External chemical stimuli act on specific cell-surface receptors of neurons resulting in an increase in the intracellular calcium ion concentration which acts as a second messenger to alter neuronal excitability. There are, however, many receptors acting through a number of closely related proteins involving complex intracellular signalling pathways which remain poorly understood. This project uses molecular, electrical and fluorescence techniques to elucidate the molecular basis for these interactions by identifying the roles individual proteins play in integrating diverse extracellular stimuli and neuronal excitablility in the peripheral nervous system.Read moreRead less
Probing the four photosynthetic membrane protein complexes at work in situ in leaves. This proposal aims at sustainable improvements in plant productivity and photosynthetic adaptation in drastic Australian climates. In photosynthesis, membranes with the four multiprotein complexes use sunlight to make compounds that drive carbon assimilation. Instead of the usual dissection of photosynthetic membranes, this project will develop and refine the applicant's rapid, reliable, non-intrusive technique ....Probing the four photosynthetic membrane protein complexes at work in situ in leaves. This proposal aims at sustainable improvements in plant productivity and photosynthetic adaptation in drastic Australian climates. In photosynthesis, membranes with the four multiprotein complexes use sunlight to make compounds that drive carbon assimilation. Instead of the usual dissection of photosynthetic membranes, this project will develop and refine the applicant's rapid, reliable, non-intrusive techniques to probe the four membrane complexes at work in their native state in leaves. Two portable commercial instruments will potentially emerge from the techniques. This novel non-reductionist approach will identify key limitations to photosynthetic performance under stress, and insights into improvements for primary plant productivity.Read moreRead less
Functional ubiquitination of neuronal voltage-gated sodium channels. Alterations in the electrical properties of excitable cells occur during tissue injury and regeneration as well as many disease states. Preventing or controlling these changes is a key strategic therapeutic aim. It is, however, only through a comprehensive understanding of the molecular mechanisms that regulate cellular excitability that we can identify these therapeutic targets. The major outcome of this project will be a thor ....Functional ubiquitination of neuronal voltage-gated sodium channels. Alterations in the electrical properties of excitable cells occur during tissue injury and regeneration as well as many disease states. Preventing or controlling these changes is a key strategic therapeutic aim. It is, however, only through a comprehensive understanding of the molecular mechanisms that regulate cellular excitability that we can identify these therapeutic targets. The major outcome of this project will be a thorough characterisation of a novel pathway that is potentially crucial in the development, homeostasis and regeneration of the nervous system. Disruption of normal function of this system may underlie the hyperexcitability observed in mannu neurodegenerative conditions.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
The Shape of Plants; Discovering factors that control morphology by organizing the cytoskeleton. Understanding how plants generate the huge diversity of shapes seen in nature is both a scientific challenge and a biotechnological opportunity. Microtubules dominate cell architecture, providing dynamic, yet rigid, frameworks for defining or changing growth polarity. We recently discovered and cloned MOR1, a gene that is essential for organizing microtubules and controlling morphogenesis. This place ....The Shape of Plants; Discovering factors that control morphology by organizing the cytoskeleton. Understanding how plants generate the huge diversity of shapes seen in nature is both a scientific challenge and a biotechnological opportunity. Microtubules dominate cell architecture, providing dynamic, yet rigid, frameworks for defining or changing growth polarity. We recently discovered and cloned MOR1, a gene that is essential for organizing microtubules and controlling morphogenesis. This places us in a strong position to resolve a long-standing mystery: how are microtubules organized? We intend to define MOR1's structural attributes, identify its interacting proteins and innovate an ambitious screen for additional genes that have related functions. This project should stimulate new ideas and applications.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