Mechanosensitive properties and modulation of N-methyl-D-aspartate (NMDA) receptors by lipid environment. This project will provide new information about the molecular determinants which influence NMDA receptor channel gating that will significantly advance our understanding of a link between NMDA receptor function and many neurodegenerative diseases as well as pain and learning and memory. The outcomes of this project may lead to the discovery of novel lipid-based biomaterials for application i ....Mechanosensitive properties and modulation of N-methyl-D-aspartate (NMDA) receptors by lipid environment. This project will provide new information about the molecular determinants which influence NMDA receptor channel gating that will significantly advance our understanding of a link between NMDA receptor function and many neurodegenerative diseases as well as pain and learning and memory. The outcomes of this project may lead to the discovery of novel lipid-based biomaterials for application in medicine and the drug industry. This research is highly significant in relation to human health. The biological and nutritional aspects of polyunsaturated lipids and dietary fish oils have long been recognized. Thus this project will provide further knowledge that could benefit the health of the nation with consequent reduced health care costs.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775613
Funder
Australian Research Council
Funding Amount
$467,000.00
Summary
Automated Patch Clamp System. Ion channels are membrane proteins that underlie cell function and are therefore important drug targets. The patch clamp technique is the most powerful tool available to study the function of single ion channels. The recent automation of this technology represents a quantum leap in our ability to perform high throughput screening of novel natural and synthetic compounds as drug leads. This will lead to an urgently needed increase in capacity, increasing the volume o ....Automated Patch Clamp System. Ion channels are membrane proteins that underlie cell function and are therefore important drug targets. The patch clamp technique is the most powerful tool available to study the function of single ion channels. The recent automation of this technology represents a quantum leap in our ability to perform high throughput screening of novel natural and synthetic compounds as drug leads. This will lead to an urgently needed increase in capacity, increasing the volume of research and its outcomes, which will benefit the Australian pharmaceutical industry and biosciences research community.
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The role of mechanosensitive (MS) ion channels in magnetoreception. The magnetic field of the Earth has for long been known to influence the behaviour and orientation of a variety of organisms. Experimental study of the magnetic sense has however, been impaired by the lack of a plausible cellular and/or molecular mechanism providing meaningful explanation for detection of magnetic fields by living organisms. Recently, mechanosensitive (MS) ion channels have been implied to play a role in magneto ....The role of mechanosensitive (MS) ion channels in magnetoreception. The magnetic field of the Earth has for long been known to influence the behaviour and orientation of a variety of organisms. Experimental study of the magnetic sense has however, been impaired by the lack of a plausible cellular and/or molecular mechanism providing meaningful explanation for detection of magnetic fields by living organisms. Recently, mechanosensitive (MS) ion channels have been implied to play a role in magnetoreception. Based on our preliminary investigations, which suggest that the activity of bacterial MS channels may be affected by magnetic fields, we propose to study effects of magnetic fields on MS ion channels in Gram-negative bacteria Escherichia coli and Magnetospirillum magnetotacticum. The project promises also to contribute towards better understanding of adverse effects of electromagnetic radiation on human health and towards understanding the mechanisms behind remote magnetic-nanoparticle mediated activation of MS ion channels.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
Molecular structure and function of the glycine receptor. This proposal will employ a cutting edge approach to reveal fundamental new insights into the ways that ligand-gated ion channels, and proteins in general, work. The new knowledge and technology developed here will broaden and strengthen Australia's research expertise across a number of basic scientific disciplines. The results will also have relevance to human health. Glycine receptors have an essential role in brain function and are ....Molecular structure and function of the glycine receptor. This proposal will employ a cutting edge approach to reveal fundamental new insights into the ways that ligand-gated ion channels, and proteins in general, work. The new knowledge and technology developed here will broaden and strengthen Australia's research expertise across a number of basic scientific disciplines. The results will also have relevance to human health. Glycine receptors have an essential role in brain function and are targets for anaesthetics and drugs of abuse. GlyRs are also important in modulating pain sensation by the brain. New insights into how natural agonists and drugs affect ion channel structure and function may lead to novel therapeutic opportunities and improved drug structure predictions.Read moreRead less
From structures to systems: A hierachical approach to understanding sub-cellular components. This program will dramatically extend the range of biomolecular systems that can be modelled with near atomistic precision. It will provide a better understanding of the structure and function of proteins involved in the regulation of membrane fusion and fission as well as shedding light on the assembly of large-scale protein-protein and protein-membrane complexes in general. The work will help place Au ....From structures to systems: A hierachical approach to understanding sub-cellular components. This program will dramatically extend the range of biomolecular systems that can be modelled with near atomistic precision. It will provide a better understanding of the structure and function of proteins involved in the regulation of membrane fusion and fission as well as shedding light on the assembly of large-scale protein-protein and protein-membrane complexes in general. The work will help place Australia at the forefront of developing simulation techniques in biomolecular systems, which are widely used within the chemical and pharmaceutical industries for modelling processes ranging from protein-drug interactions to the phase behaviour of lipids and surfactants. Read moreRead less
A new model for secreton in epithelial cells. This proposal sets out to test a new model for secretion that we have developed in the light of recent experimental data. The project outcomes will advance our understanding of normal processes of secretion and may be important in understanding disease. We will develop cutting-edge techniques of microscopy which will place Australia at the forefront of this exciting field. The project will bring benefit to the Australian scientific community through ....A new model for secreton in epithelial cells. This proposal sets out to test a new model for secretion that we have developed in the light of recent experimental data. The project outcomes will advance our understanding of normal processes of secretion and may be important in understanding disease. We will develop cutting-edge techniques of microscopy which will place Australia at the forefront of this exciting field. The project will bring benefit to the Australian scientific community through interactions and collaborations with other scientists in Australia and internationally and will benefit early-career scientists, training them in novel methods and allowing them to develop their research expertise and profile and enabling them to compete on the world science stage. Read moreRead less
Increasing the Efficiency of Biomolecular Simulations. This program will extend the range of biomolecular systems that can be modelled with near atomistic precision. It will provide a better understanding of the structure and function of proteins involved in the regulation of membrane fusion and fission as well as shedding light on the assembly of large-scale protein-protein and protein-membrane complexes in general. The work will help place Australia at the forefront of developing simulation t ....Increasing the Efficiency of Biomolecular Simulations. This program will extend the range of biomolecular systems that can be modelled with near atomistic precision. It will provide a better understanding of the structure and function of proteins involved in the regulation of membrane fusion and fission as well as shedding light on the assembly of large-scale protein-protein and protein-membrane complexes in general. The work will help place Australia at the forefront of developing simulation techniques in biomolecular systems, which are widely used within the chemical and pharmaceutical industries. It will also provide opportunities for the training and development of young Australian researchers with top European laboratories. Read moreRead less
Development of cryopreservation for high value provenance collections of recalcitrant plant species used in post-mining restoration. This project will develop new and innovative ways to store highly valued native plant germplasm at ultra cold temperatures (-196 °C, in liquid nitrogen) as a means to ensure that elite genotypes used in minesite restoration and critically endangered species are not lost forever to extinction. This project will be the first of its type in Australia utilising a multi ....Development of cryopreservation for high value provenance collections of recalcitrant plant species used in post-mining restoration. This project will develop new and innovative ways to store highly valued native plant germplasm at ultra cold temperatures (-196 °C, in liquid nitrogen) as a means to ensure that elite genotypes used in minesite restoration and critically endangered species are not lost forever to extinction. This project will be the first of its type in Australia utilising a multidisciplinary approach to answer key storage questions and will provide significant national benefits to conservation programs and landcare groups, providing these with additional resources to ensure the long-term survival of native plant germplasm collections. Read moreRead less
Structural analysis of membrane proteins using template-mediated crystallization. A new frontier technology will be developed in the form of a systematic crystallization pipeline for membrane proteins. This high throughput monolayer template technology is particularly suited for the structure determination of proteins that are otherwise difficult to crystallize and has clear commercial potential. Membrane protein structures are themselves of value to the biotechnology and pharmaceutical industry ....Structural analysis of membrane proteins using template-mediated crystallization. A new frontier technology will be developed in the form of a systematic crystallization pipeline for membrane proteins. This high throughput monolayer template technology is particularly suited for the structure determination of proteins that are otherwise difficult to crystallize and has clear commercial potential. Membrane protein structures are themselves of value to the biotechnology and pharmaceutical industry for targeted drug design, which could realise benefits in the form of novel medical treatments and reduced side effects. The monolayer template technology will also extend the capabilities of the National Cryo-EM facility, the infrastructure of which, is open for all Australian researchers. Read moreRead less