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
Control of actin assembly by cell-cell adhesion: molecular effectors and higher order function. Functional cooperation between the actin cytoskeleton and cadherin cell-cell adhesion molecules plays critical roles during development and morphogenesis. This proposal builds on my lab's recent discovery that E-cadherin interacts with and regulates the Arp2/3 actin nucleator complex, a central determinant of actin assembly in cells. We will explore key implications of this finding, concentrating on d ....Control of actin assembly by cell-cell adhesion: molecular effectors and higher order function. Functional cooperation between the actin cytoskeleton and cadherin cell-cell adhesion molecules plays critical roles during development and morphogenesis. This proposal builds on my lab's recent discovery that E-cadherin interacts with and regulates the Arp2/3 actin nucleator complex, a central determinant of actin assembly in cells. We will explore key implications of this finding, concentrating on defining the molecular mechanisms that regulate Arp2/3 and actin assembly in cadherin-based adhesion. Our work combines molecular characterization of regulatory mechanisms and proteomic searches for new regulators, with tests of the higher-order function of this novel process in cell adhesion and recognition.Read moreRead less
Balancing cadherin-actin cooperation: the key regulatory role of Ena/VASP proteins. This project analyses a fundamental mechanism of how cells work together in tissues. Understanding the fundamental mechanisms of how cells work will provide important basic scientific information to enrich the scientific expertise in Australia and its part in the international community, generate insights relevant for understanding human disease and physical degeneration, and support the training of young scienti ....Balancing cadherin-actin cooperation: the key regulatory role of Ena/VASP proteins. This project analyses a fundamental mechanism of how cells work together in tissues. Understanding the fundamental mechanisms of how cells work will provide important basic scientific information to enrich the scientific expertise in Australia and its part in the international community, generate insights relevant for understanding human disease and physical degeneration, and support the training of young scientists in Australia.Read moreRead less
A microscopical examination of curdlan production by an Agrobacterium sp. We will investigate the secretion of the insoluble polysaccharide curdlan, a (1,3)-beta-glucan, from the surfaces of Agrobacterium cells and the assembly of the individual polysaccharide chains into microfibrils. Using state-of-the-art techniques in time lapse and electron microscopy we will compare the images of wild type curdlan-producing cells with those of mutants impaired in the production of curdlan. The outputs will ....A microscopical examination of curdlan production by an Agrobacterium sp. We will investigate the secretion of the insoluble polysaccharide curdlan, a (1,3)-beta-glucan, from the surfaces of Agrobacterium cells and the assembly of the individual polysaccharide chains into microfibrils. Using state-of-the-art techniques in time lapse and electron microscopy we will compare the images of wild type curdlan-producing cells with those of mutants impaired in the production of curdlan. The outputs will be information on the mechanics of curdlan production that will complement that emerging from our molecular biological and biochemical studies. These will have implications for understanding bacterial polysaccharide production in general and may have a commercial outcome in enhanced curdlan production.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0214135
Funder
Australian Research Council
Funding Amount
$492,000.00
Summary
High performance protein crystallography. This proposal will provide state of the art high performance facilities for protein crystallography, bringing together the major structural biology groups in NSW and the ACT. A renewed focus on protein crystal structures will stimulate new interpretation and utilization of the vast amount of data that has come from genomics, especially the sequencing of the human genome. The proposed facility will generate new research collaborations between the partn ....High performance protein crystallography. This proposal will provide state of the art high performance facilities for protein crystallography, bringing together the major structural biology groups in NSW and the ACT. A renewed focus on protein crystal structures will stimulate new interpretation and utilization of the vast amount of data that has come from genomics, especially the sequencing of the human genome. The proposed facility will generate new research collaborations between the partner institutions which will result in advances in basic life sciences, biotechnology and biopharmaceuticals. The facility will complement regional initiatives in functional genomics, bioinformatics, proteomics and high-field NMR spectroscopy.Read moreRead less
Lipid raft and cyotoskeleton organization: How membrane domains give cells direction. For a large number of cells in our body it is imperative that they are able to orientate themselves relative to their environment, sense direction and translate incoming signals. To do so it is hypothesised that lipids on the cell surface are redistributed to form specialized domains. An asymmetric distribution of membrane domains can provide cells with a front and rear end and can further concentrate and co-or ....Lipid raft and cyotoskeleton organization: How membrane domains give cells direction. For a large number of cells in our body it is imperative that they are able to orientate themselves relative to their environment, sense direction and translate incoming signals. To do so it is hypothesised that lipids on the cell surface are redistributed to form specialized domains. An asymmetric distribution of membrane domains can provide cells with a front and rear end and can further concentrate and co-ordinate signalling molecules to a specific site. The project will determine the role of lipid domain in stabilizing cell shape and their remodelling during cell migration, the digestion of foreign particles and the formation of cell-cell contacts.Read moreRead less
Structures and Functions of Bacterial Replisomal Proteins. DNA replication in all organisms requires many proteins to interact in a structure called the replisome. The bacterial replisome is assembled about the DnaB helicase, a motor protein that moves along DNA, separating the strands of duplex regions in its path. This project aims to develop understanding of the chemistry of DnaB and other replisomal proteins: their structures, how they work, and how they interact to assemble the replisome. T ....Structures and Functions of Bacterial Replisomal Proteins. DNA replication in all organisms requires many proteins to interact in a structure called the replisome. The bacterial replisome is assembled about the DnaB helicase, a motor protein that moves along DNA, separating the strands of duplex regions in its path. This project aims to develop understanding of the chemistry of DnaB and other replisomal proteins: their structures, how they work, and how they interact to assemble the replisome. This has the potential to lead to design of new antibacterial drugs.
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