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
The cellulose synthase complex of the Arabidopsis primary cell wall. The polysaccharide cellulose is the basis for the wood and cotton fibre industries of Australia and much of our research on the mechanism of synthesis has been supported by those industries over the past decade. The present project focuses on the proteins making cellulose and how they organised into functional complexes that are able to make cellulose. The knowledge it provides, together with that from other projects, will move ....The cellulose synthase complex of the Arabidopsis primary cell wall. The polysaccharide cellulose is the basis for the wood and cotton fibre industries of Australia and much of our research on the mechanism of synthesis has been supported by those industries over the past decade. The present project focuses on the proteins making cellulose and how they organised into functional complexes that are able to make cellulose. The knowledge it provides, together with that from other projects, will move us towards the situation where we can manipulate the rate at which cellulose is produced and change its detailed properties. This opens the way to industry producing fibres with more desirable properties and producing novel cellulose-based materials tailored to specific applications.Read moreRead less
Functional Genomic Analysis of Exported DNAJ Molecules in the Malaria Parasite Plasmodium falciparum. Malaria is not only a global health problem, but also affects countries surrounding Australia like PNG and Indonesia, reducing the region's stability and prosperity. Environmental changes and increased mobility of people (eg. aid and security personnel) make Australia itself more prone to malaria. The project will translate recent genomic data into functional insights using frontier technology t ....Functional Genomic Analysis of Exported DNAJ Molecules in the Malaria Parasite Plasmodium falciparum. Malaria is not only a global health problem, but also affects countries surrounding Australia like PNG and Indonesia, reducing the region's stability and prosperity. Environmental changes and increased mobility of people (eg. aid and security personnel) make Australia itself more prone to malaria. The project will translate recent genomic data into functional insights using frontier technology to identify new intervention targets for P. falciparum infection. Developing novel targets is mandated by humanity, and also to safeguard Australia's region against the social and economical implication of this disease. An Australian developed intervention would increase the global visibility of its science, leading to increased investments.Read moreRead less
Sustaining neuronal communication through bulk endocytosis. Brain activities such as learning and memory rely on the ability of neurons to communicate. This research will improve our understanding of how synaptic vesicles recycle during periods of intense synaptic activity. This is a fundamental process relevant to neuronal communication, insulin release, hormone secretion, and allergic responses in health and disease and therefore has broad significance. This work will enhance Australia's exist ....Sustaining neuronal communication through bulk endocytosis. Brain activities such as learning and memory rely on the ability of neurons to communicate. This research will improve our understanding of how synaptic vesicles recycle during periods of intense synaptic activity. This is a fundamental process relevant to neuronal communication, insulin release, hormone secretion, and allergic responses in health and disease and therefore has broad significance. This work will enhance Australia's existing strength in cell biology and neuroscience and provide high quality training for an undergraduate student and post-doctoral scientist.Read moreRead less
Polysaccharide Synthase Genes in Agro-Industrial Applications. Achievement of the project aims will generate valuable intellectual property and meet National Research Priorities by: enhancing our knowledge base for the production of renewable bio-fuels from crop residues, for an environmentally sustainable Australia; developing preventative healthcare through adoption of healthier diets, rich in non-starchy cell wall polysaccharides that help reduce the incidence and severity of cardiovascular d ....Polysaccharide Synthase Genes in Agro-Industrial Applications. Achievement of the project aims will generate valuable intellectual property and meet National Research Priorities by: enhancing our knowledge base for the production of renewable bio-fuels from crop residues, for an environmentally sustainable Australia; developing preventative healthcare through adoption of healthier diets, rich in non-starchy cell wall polysaccharides that help reduce the incidence and severity of cardiovascular disease, obesity, diabetes and some cancers; and by developing breakthrough science in emerging agricultural technologies. The alliance will foster an intellectual environment to provide world-class basic research outcomes and training of highly skilled graduates, thereby contributing to the 'knowledge nation'.Read moreRead less
Investigation of a Phagocytic Synapse in the Uptake of Apoptotic Cells. Rapid clearance of cells that die by apoptosis is crucial for embryonic development, tissue turnover, and after inflammatory events. Specialised phagocytes engulf the apoptotic cell corpses in a way that minimises inflammation and prevents autoimmunity. Genetic studies have identified the key evolutionary receptors involved, but the molecular basis of this phagocytosis is still poorly understood. We have developed, and seek ....Investigation of a Phagocytic Synapse in the Uptake of Apoptotic Cells. Rapid clearance of cells that die by apoptosis is crucial for embryonic development, tissue turnover, and after inflammatory events. Specialised phagocytes engulf the apoptotic cell corpses in a way that minimises inflammation and prevents autoimmunity. Genetic studies have identified the key evolutionary receptors involved, but the molecular basis of this phagocytosis is still poorly understood. We have developed, and seek to establish, an integrated model that incorporates new findings to explain how the distinctive functions of specialised receptors can be orchestrated to achieve this function. A successful outcome to the project will provide new knowledge of value to human health.Read moreRead less