Metal-Based Anti-inflammatory Drugs with High Efficacy and Low Side-Effects. Non-steroidal anti-inflammatory drugs (NSAIDs) have widespread human and veterinary applications for the treatment of arthritis and other inflammatory diseases, but their utility is limited by often severe gastrointestinal, renal and cardiac side-effects. The recently heralded COX-2 inhibitors have not lived up to their expectations in terms of efficacy and side-effects, therefore, there is a need to develop new potent ....Metal-Based Anti-inflammatory Drugs with High Efficacy and Low Side-Effects. Non-steroidal anti-inflammatory drugs (NSAIDs) have widespread human and veterinary applications for the treatment of arthritis and other inflammatory diseases, but their utility is limited by often severe gastrointestinal, renal and cardiac side-effects. The recently heralded COX-2 inhibitors have not lived up to their expectations in terms of efficacy and side-effects, therefore, there is a need to develop new potent, but safer, NSAIDs. This project is aimed at using the results from new lead compounds to design NSAIDs with much greater efficacy and much less side effects than those currently available.Read moreRead less
Synthesis and analysis of equine anabolic steroid metabolites. The Australian Racing Industry has an annual turnover of over $11,000M and is Australia's highest employing industry. Its credibility is dependent upon the enforcement of regulations relating to illicit substances. The aim of the project is to devise testing procedures for illicit drugs in the equine. To achieve this a variety of hydroxylated anabolic steroid equine metabolites are to be synthesised as reference standards and for ....Synthesis and analysis of equine anabolic steroid metabolites. The Australian Racing Industry has an annual turnover of over $11,000M and is Australia's highest employing industry. Its credibility is dependent upon the enforcement of regulations relating to illicit substances. The aim of the project is to devise testing procedures for illicit drugs in the equine. To achieve this a variety of hydroxylated anabolic steroid equine metabolites are to be synthesised as reference standards and for studies on analytical procedures. These analytical studies will involve production of antibodies, and of the appropriate testing procedures.Read moreRead less
Novel hybrid agricultural-byproduct/synthetic materials. The French partners have developed a method of converting low-value agricultural by-products into commodity plastics; however, the results are too water-sensitive to be useful. This project is to develop the science for grafting water-resistant moieties to this product, using mechanistically-based techniques developed by the Sydney group. The outcome would be technology for making useful materials from agricultural by-products that are cur ....Novel hybrid agricultural-byproduct/synthetic materials. The French partners have developed a method of converting low-value agricultural by-products into commodity plastics; however, the results are too water-sensitive to be useful. This project is to develop the science for grafting water-resistant moieties to this product, using mechanistically-based techniques developed by the Sydney group. The outcome would be technology for making useful materials from agricultural by-products that are currently of very low value in Australia.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0883030
Funder
Australian Research Council
Funding Amount
$450,000.00
Summary
High-Resolution Field Emission Scanning Electron Microscopy (FESEM) Platform for Characterisation at the Nanometre-Level. The Field Emission Scanning Electron Microscope (FESEM) is designed to provide fundamental insights into physical and biological systems though characterisation and analysis of structures on nanometre length scales. This versatile instrument will support a wide range of research projects covering all four national research priorities. These range from the characterisation of ....High-Resolution Field Emission Scanning Electron Microscopy (FESEM) Platform for Characterisation at the Nanometre-Level. The Field Emission Scanning Electron Microscope (FESEM) is designed to provide fundamental insights into physical and biological systems though characterisation and analysis of structures on nanometre length scales. This versatile instrument will support a wide range of research projects covering all four national research priorities. These range from the characterisation of light alloys to boost and intensify Australia's aluminium, magnesium and titanium alloy industries, to tissue engineering for the repair of human elastic tissues in skin, artery, bladder and lung, to the study of microtubules in plant cells for genetic manipulation of plants to withstand environmental stresses such as drought or salinity.Read moreRead less
Characterisation of two-pore domain potassium channels: structure-function studies of the M1-P1 loops of TASK channels. TWIK-related Acid Sensitive K+ (TASK) channels are members of the novel class of two-pore domain potassium channel family. They are potently inhibited by local anaesthetics and have been implicated as having important roles in many pathophysiological conditions such as heart arrythmias, stroke, epilepsy, breast and other cancers. The in depth structural and functional character ....Characterisation of two-pore domain potassium channels: structure-function studies of the M1-P1 loops of TASK channels. TWIK-related Acid Sensitive K+ (TASK) channels are members of the novel class of two-pore domain potassium channel family. They are potently inhibited by local anaesthetics and have been implicated as having important roles in many pathophysiological conditions such as heart arrythmias, stroke, epilepsy, breast and other cancers. The in depth structural and functional characterisation of this class of potassium channels is of great importance as they are interesting targets for new therapeutic developments. Advancement of knowledge in the structure and function of these channels will underpin drug targeting that will aid preventative healthcare, allowing Australians to age well and age productively.Read moreRead less
Mass Spectrometric Investigations of Conformation and Dynamics of Biological Complexes. The new collaboration between the leading mass spectrometry groups at University Wollongong and Cambridge University will benefit both partners. Researchers at Wollongong will have access to an ion mobility mass spectrometry technology not currently available in Australia that will contribute to our understanding of complicated cellular processes such as chromosome replication. The researchers' experience wit ....Mass Spectrometric Investigations of Conformation and Dynamics of Biological Complexes. The new collaboration between the leading mass spectrometry groups at University Wollongong and Cambridge University will benefit both partners. Researchers at Wollongong will have access to an ion mobility mass spectrometry technology not currently available in Australia that will contribute to our understanding of complicated cellular processes such as chromosome replication. The researchers' experience with this technology will pave the way for introduction of the technology to Australia and benefit the wider scientific community in wide-ranging projects such as development of new antibiotics and vaccines. Students from both institutions will benefit from experiencing science from an international perspective.Read moreRead less
Electro-active and migratory peptides in lipid bilayers: NMR and biophysical studies. All living things are characterized by the separation of inner space from the surrounding medium by a self-assembling membrane. Selective entry and exit of water, ions and solutes is a defining feature of each type of cell. Some proteins sense the voltage difference across the cell membrane and open or close in response to voltage changes. Others, like bacterial toxins assemble in the membrane as pores, while o ....Electro-active and migratory peptides in lipid bilayers: NMR and biophysical studies. All living things are characterized by the separation of inner space from the surrounding medium by a self-assembling membrane. Selective entry and exit of water, ions and solutes is a defining feature of each type of cell. Some proteins sense the voltage difference across the cell membrane and open or close in response to voltage changes. Others, like bacterial toxins assemble in the membrane as pores, while other peptides migrate across the membrane piggy-backing their peptide cargo. The aim is to understand the molecular mechanisms in examples of these membrane-active peptides and proteins with a view to enabling rational intervention into their operation in situ in normal and disease states.Read moreRead less
NMR studies of membrane proteins and peptides in novel amphiphilic mesophases. Membrane proteins are the next frontier in structural biology. Our goal is the structural and mechanistic characterization of the proteins and peptides from platypus venom and a cardiac potassium ion channel, HERG, that has a particular role in the suppression of cardiac arrhythmias. To do this we will refine and develop methods using amphiphilic mesophases and micelles and state-of-the-art NMR spectroscopy. Electrop ....NMR studies of membrane proteins and peptides in novel amphiphilic mesophases. Membrane proteins are the next frontier in structural biology. Our goal is the structural and mechanistic characterization of the proteins and peptides from platypus venom and a cardiac potassium ion channel, HERG, that has a particular role in the suppression of cardiac arrhythmias. To do this we will refine and develop methods using amphiphilic mesophases and micelles and state-of-the-art NMR spectroscopy. Electrophysiological analysis of ion channels and interactions with toxins will relate NMR structures to function. The NMR methodologies we develop will have broad applicability to membrane proteins in general.
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Nuclear magnetic resonance (NMR) studies of complex cellular responses: isotopomer sub-spaces, 'lost' ATP and 'tunable' anisotropy. Red blood cells (RBCs) transport oxygen around the body but they have other roles that are mediated by complex interconnecting metabolic pathways that generate myriad metabolites including ATP. A longstanding conundrum is the inability to account for ~60% of ATP turnover in human RBCs. Processes that may consume this 'lost' ATP, include autonomous motion of the cel ....Nuclear magnetic resonance (NMR) studies of complex cellular responses: isotopomer sub-spaces, 'lost' ATP and 'tunable' anisotropy. Red blood cells (RBCs) transport oxygen around the body but they have other roles that are mediated by complex interconnecting metabolic pathways that generate myriad metabolites including ATP. A longstanding conundrum is the inability to account for ~60% of ATP turnover in human RBCs. Processes that may consume this 'lost' ATP, include autonomous motion of the cell membrane called 'flickering', and maintenance of the biconcave-disc shape. NMR spectroscopy of quadrupolar nuclei in chiral aligned media, and isotopomer analysis will be used to define the kinetics of metabolism and membrane processes and thus help define the molecular basis of major blood disorders. Read moreRead less
NMR Spectroscopy of Complex Cellular Processes. The Theme is the cell viewed as a complex regulated molecular assembly. The Aim is to establish an integrated mathematical model of red cell metabolism, membrane transport, shape, and mechanical properties, principally by using NMR spectroscopy. The Significance will be discovery of new aspects of cellular structure and function, and new NMR theory for molecular bioscience. Outcomes will include new NMR measurements of kinetics of metabolic reactio ....NMR Spectroscopy of Complex Cellular Processes. The Theme is the cell viewed as a complex regulated molecular assembly. The Aim is to establish an integrated mathematical model of red cell metabolism, membrane transport, shape, and mechanical properties, principally by using NMR spectroscopy. The Significance will be discovery of new aspects of cellular structure and function, and new NMR theory for molecular bioscience. Outcomes will include new NMR measurements of kinetics of metabolic reactions, rates of membrane transport, solute diffusion, and functions of key membrane- and cytoskeletal proteins. Practical applications will include strategies for modelling complex biochemical systems, and circumventing metabolic defects arising from inheritance, the environment, and therapies.Read moreRead less