Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100142
Funder
Australian Research Council
Funding Amount
$500,000.00
Summary
An integrated liquid chromatography mass spectrometry nuclear magnetic resonance (LC-MS-NMR) facility for applications in proteomics and organic chemistry. This application completes the requested liquid chromatography mass spectrometry nuclear magnetic resonance (LCMS-NMR) facility and will allow the training of over 150 researchers, significantly enhancing their research productivity and translation of outcomes in areas of national importance. New breakthroughs in drug development, smart mate ....An integrated liquid chromatography mass spectrometry nuclear magnetic resonance (LC-MS-NMR) facility for applications in proteomics and organic chemistry. This application completes the requested liquid chromatography mass spectrometry nuclear magnetic resonance (LCMS-NMR) facility and will allow the training of over 150 researchers, significantly enhancing their research productivity and translation of outcomes in areas of national importance. New breakthroughs in drug development, smart materials, organic electronic materials and biomedical research require routine access to cutting edge technology. The LCMS-NMR augments the capabilities of our research teams at the forefront of these efforts. These include understanding the impact of the environment on plant and animal development, pest animal control, development of new biotechnology tools, new drugs and new methods for the detection of narcotics and explosives.Read moreRead less
Novel target of amiloride analogues - picornaviral RNA polymerase. Picornaviruses cause a range of diseases such as poliomyelitis, meningitis, myocarditis, hepatitis A, neonatal sepsis and common cold. No antiviral treatment is available for these infections. Nearly 50% of antiviral drugs used in medicine are viral polymerase inhibitors; however picornaviral RNA polymerase has been largely overlooked as a drug target. We have discovered a group of compounds that inhibit picornaviral RNA polymera ....Novel target of amiloride analogues - picornaviral RNA polymerase. Picornaviruses cause a range of diseases such as poliomyelitis, meningitis, myocarditis, hepatitis A, neonatal sepsis and common cold. No antiviral treatment is available for these infections. Nearly 50% of antiviral drugs used in medicine are viral polymerase inhibitors; however picornaviral RNA polymerase has been largely overlooked as a drug target. We have discovered a group of compounds that inhibit picornaviral RNA polymerase. This project aims to define the inhibition mechanism and to evaluate a potential use of these compounds for antiviral drug development.Read moreRead less
Membrane structure and lipid interactions of the pore-forming toxin Equinatoxin II by NMR. The structure of Equinatoxin II, a pore-forming protein, will be determined in model cell membranes using solid-state NMR spectroscopy. The relationship of molecular structure to bioactivity and the nature of the pore-forming mechanism of this toxin will be determined. The results will aid in understanding how toxins lyse cells and could lead to the design of improved antibiotic peptides. Currently the st ....Membrane structure and lipid interactions of the pore-forming toxin Equinatoxin II by NMR. The structure of Equinatoxin II, a pore-forming protein, will be determined in model cell membranes using solid-state NMR spectroscopy. The relationship of molecular structure to bioactivity and the nature of the pore-forming mechanism of this toxin will be determined. The results will aid in understanding how toxins lyse cells and could lead to the design of improved antibiotic peptides. Currently the structure of membrane proteins are difficult to determine and the newly developed techniques used for the structural determination of this membrane-associated protein will be suitable for studying other membrane proteins and receptors of pharmaceutical importance.Read moreRead less
New polymerisation processes for the synthesis of novel biopolymers. Synthetic peptide-based vaccines, formed via polymerisation of small bioactive motifs, possess several advantages over traditional approaches and promise to be the multi-disease targeting vaccines of the future. Disease targets will include influenza and hepatitis C viruses and a toxin from enteropathogenic Escherichia coli. These three diseases are in desperate need of novel vaccine approaches and the chemistries described in ....New polymerisation processes for the synthesis of novel biopolymers. Synthetic peptide-based vaccines, formed via polymerisation of small bioactive motifs, possess several advantages over traditional approaches and promise to be the multi-disease targeting vaccines of the future. Disease targets will include influenza and hepatitis C viruses and a toxin from enteropathogenic Escherichia coli. These three diseases are in desperate need of novel vaccine approaches and the chemistries described in this proposal represent a conceptual leap over traditional, and so far ineffective approaches investigated thus far. Synthetic antifreeze proteins and bioelastomers will also be constructed using our catalysis driven polymerisation process and applied to unmet medical and industrial needs.Read moreRead less
New methods for the synthesis of stable cyclic peptides. This proposal will design, synthesise and evaluate novel carbocyclic analogues of cyclic peptides which have application in the treatment of pain, diabetes management, malaria, and cancer therapy and diagnosis. The carbocyclic analogues will have improved biostability and will also provide the opportunity for oral administration. Carbacyclic analogues of insulin could lead to improved treatment of Australia's 1.2 million diabetics includi ....New methods for the synthesis of stable cyclic peptides. This proposal will design, synthesise and evaluate novel carbocyclic analogues of cyclic peptides which have application in the treatment of pain, diabetes management, malaria, and cancer therapy and diagnosis. The carbocyclic analogues will have improved biostability and will also provide the opportunity for oral administration. Carbacyclic analogues of insulin could lead to improved treatment of Australia's 1.2 million diabetics including many Aboriginal Australians who are particularly susceptible to Type II diabetes and its debilitating complications.Read moreRead less
New analgesics based on µ-conotoxins: structure-based design of helical mimetics. Diseases in which voltage-gated sodium channels are implicated are contributors to morbidity and mortality in the Australian population, and this project promises to provide new leads for the future development of drugs to treat such diseases, in particular analgesics for the treatment of chronic pain. The generation of these leads will entail the development of new approaches to mimicking key regions of peptides a ....New analgesics based on µ-conotoxins: structure-based design of helical mimetics. Diseases in which voltage-gated sodium channels are implicated are contributors to morbidity and mortality in the Australian population, and this project promises to provide new leads for the future development of drugs to treat such diseases, in particular analgesics for the treatment of chronic pain. The generation of these leads will entail the development of new approaches to mimicking key regions of peptides and proteins in drug-like molecules. This is a highly interdisciplinary project, spanning structural biology, molecular design, medicinal chemistry, molecular biology and electrophysiology, and the training of PhD graduates with such broad experience represents another national benefit of the project.Read moreRead less
Protein And Peptide Alpha Turns. All life is controlled by the structures and functions of proteins. Major components of proteins are alpha helices that are combinations of alpha turns. Different types of alpha turns exist in proteins but have not been well studied. This project will discover and classify alpha turns in proteins, create the first small molecules that contain alpha turns outside of complex protein environments, and provide a better understanding of their chemical, structural and ....Protein And Peptide Alpha Turns. All life is controlled by the structures and functions of proteins. Major components of proteins are alpha helices that are combinations of alpha turns. Different types of alpha turns exist in proteins but have not been well studied. This project will discover and classify alpha turns in proteins, create the first small molecules that contain alpha turns outside of complex protein environments, and provide a better understanding of their chemical, structural and biological properties. Results will teach scientists important details about protein structure and function, train scientists at a frontier of chemistry-biology research, and may contribute to national priorities by triggering new approaches to medicines and novel materials.Read moreRead less
Development of Novel Detergents for Green Solvent Systems and Their Self-Assembly into Nanostructures. Successful outcomes from this collaborative project will lead to the development of new commercially viable green solvent systems for the chemical industry, e.g. dry cleaning. This has the potential to impact the community on the economic and environmental level, by significantly reducing the costs of current green solvent systems, resulting in greater likelihood of conventional toxic solvent ....Development of Novel Detergents for Green Solvent Systems and Their Self-Assembly into Nanostructures. Successful outcomes from this collaborative project will lead to the development of new commercially viable green solvent systems for the chemical industry, e.g. dry cleaning. This has the potential to impact the community on the economic and environmental level, by significantly reducing the costs of current green solvent systems, resulting in greater likelihood of conventional toxic solvents being replaced. The project will also expand the training of junior and early career scientists by allowing them to work in overseas laboratories.Read moreRead less
New Polymers for Cellulose-based Bioplastics. We will design new cellulose derivatives by combining carefully engineered synthetic polymers to cellulose. We will explore the fundamental science underpinning the manufacture of these bioplastics, and apply the concept to the design of two new materials, with (super)hydrophobic and antibacterial properties. These materials have the potential to replace synthetic plastics, which comprise one of the major outputs of the chemical industry worldwide. P ....New Polymers for Cellulose-based Bioplastics. We will design new cellulose derivatives by combining carefully engineered synthetic polymers to cellulose. We will explore the fundamental science underpinning the manufacture of these bioplastics, and apply the concept to the design of two new materials, with (super)hydrophobic and antibacterial properties. These materials have the potential to replace synthetic plastics, which comprise one of the major outputs of the chemical industry worldwide. Plastic is present everywhere in human life, but its manufacture and disposal have a strong negative impact on the environment; the new materials manufactured in this project are viable alternatives to plastics, and are sustainable from a production and disposal point of view.Read moreRead less
Synthesis and Characterisation of Encoded Hybrid Polymer/Gold Nanoparticles for Application in Bioassays. Bioassays are the cornerstone of in vitro diagnostic and biomedical research. This proposal will significantly contribute to these areas, by targeting an emerging technology that is crucial for their future development. The hybrid nanoparticles described in this project have the potential to replace conventional detection strategies that are currently used for bioassays. In doing so, they sh ....Synthesis and Characterisation of Encoded Hybrid Polymer/Gold Nanoparticles for Application in Bioassays. Bioassays are the cornerstone of in vitro diagnostic and biomedical research. This proposal will significantly contribute to these areas, by targeting an emerging technology that is crucial for their future development. The hybrid nanoparticles described in this project have the potential to replace conventional detection strategies that are currently used for bioassays. In doing so, they should provide significant advantages over conventional detection strategies. These advantages include increased sample throughput and conservation of biological samples, which makes possible the acceleration of patient diagnosis and drug discovery. Read moreRead less