Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668526
Funder
Australian Research Council
Funding Amount
$542,000.00
Summary
Biomolecular discovery and analysis facility. This facility will provide Australian researchers with unrivalled access to advanced cell visualisation and analysis tools, which until very recently were only available to the pharmaceutical industry and large US and European institutions. The facility will allow new approaches to identifying novel natural products and understanding cell signalling pathways. Knowledge of these pathways and the identification of molecules that can affect them are key ....Biomolecular discovery and analysis facility. This facility will provide Australian researchers with unrivalled access to advanced cell visualisation and analysis tools, which until very recently were only available to the pharmaceutical industry and large US and European institutions. The facility will allow new approaches to identifying novel natural products and understanding cell signalling pathways. Knowledge of these pathways and the identification of molecules that can affect them are keys to understanding normal cellular physiology and identifying drug-like molecules able to inhibit malfunctioning pathways found in different disease such as cancer. The facility will accellerate drug discovery and basic research in cell biology and underpin National Research Priorities.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882864
Funder
Australian Research Council
Funding Amount
$260,000.00
Summary
High Speed Fluorescence Imaging coupled with Total Internal Reflection Microscopy and Fluorescence Recovery After Photobleaching System. The addition of the TIRF equipment will provide researchers with access to one of Australia's most technologically advanced light microscopy systems. This system will support research across a number of high profile areas, and promote strategic collaborations in cell and neurobiology. The high resolution fast acquisition TIRF system will significantly enhance r ....High Speed Fluorescence Imaging coupled with Total Internal Reflection Microscopy and Fluorescence Recovery After Photobleaching System. The addition of the TIRF equipment will provide researchers with access to one of Australia's most technologically advanced light microscopy systems. This system will support research across a number of high profile areas, and promote strategic collaborations in cell and neurobiology. The high resolution fast acquisition TIRF system will significantly enhance research capacity and research excellence. Its acquisition will allow Australia to play a major role in the global challenge to advance understanding of cellular and molecular events, contributing significantly to the National Research Priority Area of Frontier Technologies for Building and Transforming Australian Industries.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
Early evolutionary origins of mechanosensory transduction: structure, function and phylogenetic studies of the family of mechanosensitive channels in cell-walled organisms. The proposed project is based on the recent progress the applicants have made by (i) identifying a novel family of mechanosensitive (MS) channels in cell-walled organisms, which include Archaea and Bacteria (prokaryotes), as well as fungi and plants (eukaryotes), and (ii) determining basic aspects of the structural dynamics ....Early evolutionary origins of mechanosensory transduction: structure, function and phylogenetic studies of the family of mechanosensitive channels in cell-walled organisms. The proposed project is based on the recent progress the applicants have made by (i) identifying a novel family of mechanosensitive (MS) channels in cell-walled organisms, which include Archaea and Bacteria (prokaryotes), as well as fungi and plants (eukaryotes), and (ii) determining basic aspects of the structural dynamics of MscL, the prototype MS channel, using electronparamagnetic resonance spectroscopy and molecular dynamics simulations in combination with the patch clamp technique. The aim of the project is to elucidate the molecular principles underlying the function of MS channels, which is of fundamental importance for understanding of the biophysics and physiology of mechanosensory transduction throughout the biological world.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
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
Membrane excitability and cellular calcium regulation in the peripheral nervous system under different (patho)-physiological conditions and in inflammatory disease. Studies of cytokine action on neurons and muscle give new insights into functional responses of the nervous system to systemic inflammation and sepsis. In some countries, sepsis is the third most frequent cause of death following heart attack. Elucidating the pathomechanisms allows to develop therapeutic strategies. Electrophysiology ....Membrane excitability and cellular calcium regulation in the peripheral nervous system under different (patho)-physiological conditions and in inflammatory disease. Studies of cytokine action on neurons and muscle give new insights into functional responses of the nervous system to systemic inflammation and sepsis. In some countries, sepsis is the third most frequent cause of death following heart attack. Elucidating the pathomechanisms allows to develop therapeutic strategies. Electrophysiology, Ca2+ regulation and optical membrane potentiometry allow us to monitor early changes in disease on a (sub)cellular level. Experiments on Ca2+ regulation and ion channel function in muscle with different cholesterol membrane contents will help to understand pathomechanisms in high cholesterol diseases, e.g. obesity, on the membrane level long before cardiovascular effects become prominent.Read moreRead less
Alpha-Conotoxins: Selective Probes For Nicotinic Receptor Subtype Structure And Function. Marine snails from the waters off the Australian coast produce an amazing variety of mini-proteins in their venoms called conotoxins that they use to capture prey. These conotoxins bind very specifically to receptors in our body associated with the transmission of nerve signals. We will use natural and synthetically modified conotoxins to selectively block particular types of neuronal 'receptors' to gain a ....Alpha-Conotoxins: Selective Probes For Nicotinic Receptor Subtype Structure And Function. Marine snails from the waters off the Australian coast produce an amazing variety of mini-proteins in their venoms called conotoxins that they use to capture prey. These conotoxins bind very specifically to receptors in our body associated with the transmission of nerve signals. We will use natural and synthetically modified conotoxins to selectively block particular types of neuronal 'receptors' to gain a greater understanding of how the nervous system functions. This knowledge will help in the design of new drugs to treat a variety of diseases and disorders. Essentially we will use a chemical armoury developed by the cone snail to design state-of-the-art mini-protein drugs.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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Conotoxins: Novel probes for ion channel structure and function. Voltage-dependent and ligand-gated ion channels are intrinsic membrane proteins that play a central role in communication in excitable cells, particularly in the nervous system. The primary goals of this project are (i) to define at a molecular level, the structural and functional determinants of ion channel/conotoxin interactions and (ii) develop new probes that advance neurophysiological research. The diversity and distribution o ....Conotoxins: Novel probes for ion channel structure and function. Voltage-dependent and ligand-gated ion channels are intrinsic membrane proteins that play a central role in communication in excitable cells, particularly in the nervous system. The primary goals of this project are (i) to define at a molecular level, the structural and functional determinants of ion channel/conotoxin interactions and (ii) develop new probes that advance neurophysiological research. The diversity and distribution of ion channel types and subtypes being uncovered through the use of molecular biology and conotoxin probes presents an exciting opportunity for the future development of novel ion channel therapeutics.Read moreRead less