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Discovery and applications of circular proteins. The many national benefits that will flow from this program include (i) new knowledge in plant biochemistry, peptide chemistry and protein engineering protected by a strong intellectual property position that will give Australia a competitive edge in relevant biotechnology applications; (ii) the training of a new generation of skilled researchers to drive a sustainable biotechnology sector in Australia; (iii) economic benefits from royalty returns ....Discovery and applications of circular proteins. The many national benefits that will flow from this program include (i) new knowledge in plant biochemistry, peptide chemistry and protein engineering protected by a strong intellectual property position that will give Australia a competitive edge in relevant biotechnology applications; (ii) the training of a new generation of skilled researchers to drive a sustainable biotechnology sector in Australia; (iii) economic benefits from royalty returns on drugs and agricultural products that will likely arise from the program; (iv) environment benefits due to a reduced need for chemical insecticides; and (v) social benefits due to a reduction in suffering from diseases for which drugs are developed as a result of this program.Read moreRead less
The role of gamma glutamyl cyclotransferase in glutathione homeostasis. The aim of this study is to understand the structure and function of gamma-glutamyl cyclotransferase (GGCT) and its role in glutathione synthesis and turnover. Glutathione is essential for life and serves multiple biological functions protecting against oxidative stress, and aiding in the detoxification and excretion of foreign chemicals. This study will explore a new approach to changing intracellular glutathione concentra ....The role of gamma glutamyl cyclotransferase in glutathione homeostasis. The aim of this study is to understand the structure and function of gamma-glutamyl cyclotransferase (GGCT) and its role in glutathione synthesis and turnover. Glutathione is essential for life and serves multiple biological functions protecting against oxidative stress, and aiding in the detoxification and excretion of foreign chemicals. This study will explore a new approach to changing intracellular glutathione concentrations that has wide applications in the treatment of inherited enzyme deficiencies, cancer and the development of herbicide resistant crop plants. The study will also contribute to the training of scientists for the future development of the Australian biotechnology industryRead moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989374
Funder
Australian Research Council
Funding Amount
$550,000.00
Summary
South Australian High-Resolution and Ion-Mobility Mass Spectrometry Facility. The analytical facility will enhance (i) fundamental research to understand the mechanisms of the reactions of charged species with neutral molecules, and (ii) the provision of structural information, including the precise atomic composition of any molecule, small or large. Research supported by this facility includes (a)nanotechnology, including supramolecular chemistry, (b) bioscience: cancer research, neurodegenera ....South Australian High-Resolution and Ion-Mobility Mass Spectrometry Facility. The analytical facility will enhance (i) fundamental research to understand the mechanisms of the reactions of charged species with neutral molecules, and (ii) the provision of structural information, including the precise atomic composition of any molecule, small or large. Research supported by this facility includes (a)nanotechnology, including supramolecular chemistry, (b) bioscience: cancer research, neurodegenerate diseases (e.g. Parkinson's disease) osteoarthritis, inflammation, cardiac diseases and synthetic approaches to anticancer and other drugs.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE170101438
Funder
Australian Research Council
Funding Amount
$360,000.00
Summary
Application of boronate ester-appended scaffolds in drug-discovery. This project aims to improve carbohydrate synthesis. Glycochemistry is an increasingly important chemical science that combines organic synthesis with biology. This project will develop methodologies that incorporate boronate ester residues onto selected carbons of monosaccharides and transform them to obtain hitherto inaccessible scaffolds for drug discovery. This strategy can be used in the controlled assembly of other biologi ....Application of boronate ester-appended scaffolds in drug-discovery. This project aims to improve carbohydrate synthesis. Glycochemistry is an increasingly important chemical science that combines organic synthesis with biology. This project will develop methodologies that incorporate boronate ester residues onto selected carbons of monosaccharides and transform them to obtain hitherto inaccessible scaffolds for drug discovery. This strategy can be used in the controlled assembly of other biologically important compounds, including azacycles, oxacycles and inositols. The methods for the controlled diversification of carbohydrates are expected to be broadly applicable to scientific endeavours ranging from glycobiology to medicine. Successful execution will provide new drug-discovery tools and ensure Australia secures a competitive position in this rapidly expanding discipline.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0560751
Funder
Australian Research Council
Funding Amount
$432,474.00
Summary
Facility for the Analysis of Biomacromolecular Interactions. A facility for the analysis of biological macromolecules and their interactions with ligand molecules is required to support a large number of research projects in high priority areas including mechanisms of aging, drug development and bio/nanotechnology at three different universities. The instrumentation will (i) afford quantitative measurements of binding affinities between biological and chemical macromolecules, which are available ....Facility for the Analysis of Biomacromolecular Interactions. A facility for the analysis of biological macromolecules and their interactions with ligand molecules is required to support a large number of research projects in high priority areas including mechanisms of aging, drug development and bio/nanotechnology at three different universities. The instrumentation will (i) afford quantitative measurements of binding affinities between biological and chemical macromolecules, which are available only in small quantities, and small, drug related molecules (by microcalorimetry and dual polarization interferometry), and (ii) provide equipment necessary for sample characterization and purification prior to quantitative measurements (CD spectroscopy, and FPLC equipment).Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE170100075
Funder
Australian Research Council
Funding Amount
$315,000.00
Summary
Acoustic liquid handling robotics for bioactive compound discovery. This project aims to use a Labcyte Echo 550 acoustic dispenser with Combination Software to deliver sophisticated assay-ready screening. The Echo is the only liquid handling dispenser for 1536-well microplates and will allow Australian researchers to develop assay miniaturisation. The robotics will provide our nation’s researchers with a distinct competitive edge by enhancing assay sophistication, accuracy and reproducibility wh ....Acoustic liquid handling robotics for bioactive compound discovery. This project aims to use a Labcyte Echo 550 acoustic dispenser with Combination Software to deliver sophisticated assay-ready screening. The Echo is the only liquid handling dispenser for 1536-well microplates and will allow Australian researchers to develop assay miniaturisation. The robotics will provide our nation’s researchers with a distinct competitive edge by enhancing assay sophistication, accuracy and reproducibility while reducing cost. The expected benefits will advance the elucidation of molecular mechanisms involved in complex biological phenomena. The benefits of this are substantial, including reduction in test compound and reagents, which in turn reduces laboratory costs, conserves cells and increases data quality.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0453832
Funder
Australian Research Council
Funding Amount
$550,910.00
Summary
New directions in biomolecular mass spectrometry. The combined UoW/ANU mass spectrometry facility supports a range of research projects in high priority areas including proteomics, mechanisms of aging, anticancer drugs and pathogenicity. The facility has several key deficiencies: 1) the ability to study very high molecular weight biomolecular complexes, 2) the ability to study ion-molecule interactions that have implications in mechanisms of chemistry in nature, and 3) researchers at ANU lack es ....New directions in biomolecular mass spectrometry. The combined UoW/ANU mass spectrometry facility supports a range of research projects in high priority areas including proteomics, mechanisms of aging, anticancer drugs and pathogenicity. The facility has several key deficiencies: 1) the ability to study very high molecular weight biomolecular complexes, 2) the ability to study ion-molecule interactions that have implications in mechanisms of chemistry in nature, and 3) researchers at ANU lack essential walk-up access to high sensitivity protein sequence analysis (MS/MS). The placement of resources that address these deficiencies in one geographical region and collaboration between these institutions will produce a research interaction unique in Australia.Read moreRead less
Voltage-dependent structural changes in voltage-gated sodium channels. This project aims to provide insights into the structural rearrangements experienced by Nav channels, which are key components of animal nervous systems. Voltage-gated sodium (Nav) channels initiate action potentials in excitable cells. They open in response to membrane depolarisation then rapidly inactivate. Eukaryotic Nav channels contain four unique voltage-sensor domains (VSDs) that control how the channel responds to mem ....Voltage-dependent structural changes in voltage-gated sodium channels. This project aims to provide insights into the structural rearrangements experienced by Nav channels, which are key components of animal nervous systems. Voltage-gated sodium (Nav) channels initiate action potentials in excitable cells. They open in response to membrane depolarisation then rapidly inactivate. Eukaryotic Nav channels contain four unique voltage-sensor domains (VSDs) that control how the channel responds to membrane potential changes. Recently reported crystal structures of bacterial Nav channels have greatly advanced the field, but these channels contain four identical VSDs and have different inactivation properties. Thus, much remains to be learnt about the conformational plasticity of eukaryotic Nav channel VSDs. The project plans to use animal toxins to capture eukaryotic VSDs in defined states of the gating cycle for detailed structural analysis using nuclear magnetic resonance and X-ray crystallography.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882289
Funder
Australian Research Council
Funding Amount
$520,000.00
Summary
New generation mass spectrometers for characterisation of molecular shape and size. The ion mobility mass spectrometer (IMMS at UOW) will be the first of its kind in Australia, and together with the ion trap mass spectrometer (ITMS at ANU) will continue the tradition of this partnership in providing researchers with cutting-edge instrumentation for nationally and internationally important projects including: (i) fundamental understanding of the ways in which biomolecules recognize one another, ( ....New generation mass spectrometers for characterisation of molecular shape and size. The ion mobility mass spectrometer (IMMS at UOW) will be the first of its kind in Australia, and together with the ion trap mass spectrometer (ITMS at ANU) will continue the tradition of this partnership in providing researchers with cutting-edge instrumentation for nationally and internationally important projects including: (i) fundamental understanding of the ways in which biomolecules recognize one another, (ii) investigating the structure(s) of lipids (fats) in cardiovascular disease and cataract, (iii) developing anticancer drugs, and (iv) development of new materials.Read moreRead less
Selectively targeting cancer and infectious disease with fragment-based drug discovery. Finding better compounds as starting points is one of the major challenges for drug discovery research. Fragments are small, weak binding molecules that can be upsized into drug leads with better properties when compared to starting with larger molecules. This project addresses two weaknesses of current fragment based drug discovery (FBDD) methods: first, the limitations associated with screening fragments; a ....Selectively targeting cancer and infectious disease with fragment-based drug discovery. Finding better compounds as starting points is one of the major challenges for drug discovery research. Fragments are small, weak binding molecules that can be upsized into drug leads with better properties when compared to starting with larger molecules. This project addresses two weaknesses of current fragment based drug discovery (FBDD) methods: first, the limitations associated with screening fragments; and second, the quality of commercial fragment libraries. This project anticipates that the findings will establish a commanding role for both mass spectrometry and three-dimensional fragments in advancing FBDD approaches. It also expects to identify fragments with favourable development prospects towards the next generation of therapeutics.Read moreRead less