Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882295
Funder
Australian Research Council
Funding Amount
$225,000.00
Summary
X-ray crystallography resource for membrane proteins and large macromolecular complexes. Structural biology is the underpinning of biotechnology, biopharmaceuticals and rational therapeutic design. The most successful technique for determining the structures of proteins and large macromolecular complexes is x-ray crystallography. This proposal will set up a network of state of the art resources in the Sydney region to capitalise on expertise in these areas. The facilities will foster basic re ....X-ray crystallography resource for membrane proteins and large macromolecular complexes. Structural biology is the underpinning of biotechnology, biopharmaceuticals and rational therapeutic design. The most successful technique for determining the structures of proteins and large macromolecular complexes is x-ray crystallography. This proposal will set up a network of state of the art resources in the Sydney region to capitalise on expertise in these areas. The facilities will foster basic research and collaborations with industry, which will enhance Australia's profile and commercialisation of research. The facility will enhance the usage of the Australian synchrotron, producing flagship projects on the edge of technical possibilities.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
Monolayer crystallization of membrane proteins. Membrane proteins comprise 25-40% of all proteins and conduct a myriad of finely tuned reactions in every cell. Despite their importance and diversity only ~40 membrane protein structures have been solved, due to the difficulty of producing high quality 2D and 3D crystals. We propose to develop and use the new monolayer crystallization technique, which employs a lipid monolayer as a crystallization template for 2D crystal production. A number of ....Monolayer crystallization of membrane proteins. Membrane proteins comprise 25-40% of all proteins and conduct a myriad of finely tuned reactions in every cell. Despite their importance and diversity only ~40 membrane protein structures have been solved, due to the difficulty of producing high quality 2D and 3D crystals. We propose to develop and use the new monolayer crystallization technique, which employs a lipid monolayer as a crystallization template for 2D crystal production. A number of important membrane proteins are available for these structural studies including ABC transporters, Caveolin-3 and the NS1 protein of Dengue virus, all of which are difficult to crystallize using conventional techniques.Read moreRead less
Function and regulation of the Na+,K+-ATPase. The Na+,K+-ATPase is the major energy-consuming enzyme of animal cells. Its ion pumping is essential for numerous physiological functions (e.g. heart, kidney, brain). Molecular detail of its pumping mechanism is, however, lacking and its regulation is still unclear. We will use rapid reaction methods on purified enzyme in vitro to locate the rate-determining step of the enzyme cycle, determine its mechanism, investigate its regulation by sodium conce ....Function and regulation of the Na+,K+-ATPase. The Na+,K+-ATPase is the major energy-consuming enzyme of animal cells. Its ion pumping is essential for numerous physiological functions (e.g. heart, kidney, brain). Molecular detail of its pumping mechanism is, however, lacking and its regulation is still unclear. We will use rapid reaction methods on purified enzyme in vitro to locate the rate-determining step of the enzyme cycle, determine its mechanism, investigate its regulation by sodium concentration, phosphorylation and membrane composition, and isolate its charge-transporting steps. The results will have immediate impact on the understanding of the enzyme's mechanism, its metabolic control and its role in disease.Read moreRead less
Three-dimensional structures, substrate specificities and catalytic mechanisms of polysaccharide synthases. Plant wall polysaccharides are extensively used for food and fibre, and are important dietary components in human nutrition. A precise knowledge of mechanisms used by plants to synthesize these polysaccharides is unavailable, but would reveal potential routes to manipulate their biosynthesis in important crop species. For example, the levels or structures of polysaccharides might be modif ....Three-dimensional structures, substrate specificities and catalytic mechanisms of polysaccharide synthases. Plant wall polysaccharides are extensively used for food and fibre, and are important dietary components in human nutrition. A precise knowledge of mechanisms used by plants to synthesize these polysaccharides is unavailable, but would reveal potential routes to manipulate their biosynthesis in important crop species. For example, the levels or structures of polysaccharides might be modified to improve their efficacy as anti-cancer agents in human diets, to enhance digestibility of animal stock feeds, or to synthesise pharmologically valuable compounds. Thus, economic, social and environmental benefits will flow to both producers and consumers. Read moreRead less
Role of 3'-phosphorylated phosphoinositides in neurosecretion. Neurons communicate through the release of neurotransmitter by synaptic vesicles. Minute changes underlie normal processes such as memory and modifications of neurotransmitter level contribute to a number of neurological diseases. I am interested in deciphering the role of phosphoinositides, an inner membrane-based lipid, during steps leading to the fusion of a synaptic vesicle with the plasma membrane. I have recently discovered tha ....Role of 3'-phosphorylated phosphoinositides in neurosecretion. Neurons communicate through the release of neurotransmitter by synaptic vesicles. Minute changes underlie normal processes such as memory and modifications of neurotransmitter level contribute to a number of neurological diseases. I am interested in deciphering the role of phosphoinositides, an inner membrane-based lipid, during steps leading to the fusion of a synaptic vesicle with the plasma membrane. I have recently discovered that phosphatidylinositol-3 phosphate production was critical for the vesicle to acquire the competence to fuse with the plasma membrane. This project aim to understand by which mechanism this lipid interacts with the release machinery to promote such priming step.Read moreRead less