Gas Phase Dynamics of a Biological Molecular Machine: Fundamentals, Stoichiometries and Stabilities. Over the last twenty years advanced molecular measurement techniques have enabled the characterization of individual biological molecules (proteins and DNA) within different types of cells and diseased tissues. This project uses a new technique that literally "weighs" groups of proteins and/or DNA to help us understand how such large molecules fit together and function within cells (sometimes ref ....Gas Phase Dynamics of a Biological Molecular Machine: Fundamentals, Stoichiometries and Stabilities. Over the last twenty years advanced molecular measurement techniques have enabled the characterization of individual biological molecules (proteins and DNA) within different types of cells and diseased tissues. This project uses a new technique that literally "weighs" groups of proteins and/or DNA to help us understand how such large molecules fit together and function within cells (sometimes referred to as molecular machinery). More detailed knowledge of processes such as those involved in copying DNA when new cells are produced will, in the long term, improve our understanding and treatment of conditions or diseases that result from errors in molecular machinery. Read moreRead less
Antifreeze Proteins and Glycoproteins. Antifreeze proteins and glycoproteins permit many species of fish to survive in sub-zero oceans without freezing. These antifreeze compounds have potential applications in the frozen food industry (eg. maintaining the texture of ice cream), medical science (eg., cryosurgery) and veterinary science (eg. storage of sperm). Commercial applications are limited by the amounts of compounds available from fish and the lack of understanding of how these proteins ....Antifreeze Proteins and Glycoproteins. Antifreeze proteins and glycoproteins permit many species of fish to survive in sub-zero oceans without freezing. These antifreeze compounds have potential applications in the frozen food industry (eg. maintaining the texture of ice cream), medical science (eg., cryosurgery) and veterinary science (eg. storage of sperm). Commercial applications are limited by the amounts of compounds available from fish and the lack of understanding of how these proteins work. This research will study how natural and synthetic antifreezes inhibit ice growth in order to allow the rational design of new antifreezes and will identify new compounds with potential commercial applications as cryoprotectants.Read moreRead less
Structure and activity of host-defence peptides from Australian anurans: anticancer agents, neuropeptides and nNOS inhibitors. We have discovered peptides that may have clinical applications. This is significant as these molecules may have one or more of the following properties. They may have anti-cancer effects; they may increase the effectiveness of the immune system by enhancing lymphocyte formation; and, they may act to reduce inflammation, stroke or cardiac conditions by controlling nitri ....Structure and activity of host-defence peptides from Australian anurans: anticancer agents, neuropeptides and nNOS inhibitors. We have discovered peptides that may have clinical applications. This is significant as these molecules may have one or more of the following properties. They may have anti-cancer effects; they may increase the effectiveness of the immune system by enhancing lymphocyte formation; and, they may act to reduce inflammation, stroke or cardiac conditions by controlling nitric oxide formation. Another national benefit is that personnel involved in this project are trained to the highest international standards in peptide chemistry/mass spectrometry/nuclear magnetic resonance: currently, there are not enough trained scientists in this area to meet demand.Read moreRead less
Biologically active peptides and proteins from anurans: the relationship between structure and activity. We have identified peptides (from glands of frogs and toads), some of which are amongst the most powerful biologically active compounds in the animal kingdom. The aims of this project are to investigate the relationship between the structure and bioactivity of chosen groups of peptides including pheromones, anticancer and antibiotic peptides, and peptides which inhibit neuronal nitric oxide ....Biologically active peptides and proteins from anurans: the relationship between structure and activity. We have identified peptides (from glands of frogs and toads), some of which are amongst the most powerful biologically active compounds in the animal kingdom. The aims of this project are to investigate the relationship between the structure and bioactivity of chosen groups of peptides including pheromones, anticancer and antibiotic peptides, and peptides which inhibit neuronal nitric oxide synthase. It would be of national benefit if any of these peptides have applied application, e.g. if we can use the sex pheromone of the cane toad to reduce its population, or if we can produce an anticancer active peptide of clinical applicability.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
Refinement of dynamic combinatorial chemistry as a drug discovery tool. Medicinal chemistry is constantly being challenged to develop efficient methodologies for the synthesis of compounds for drug discovery. Following completion of the Human Genome project, the cloning and expression of new proteins will proceed at an accelerated rate. In the absence of biochemical knowledge of the target protein there is a growing interest in techniques that expand the structural and biological diversity of co ....Refinement of dynamic combinatorial chemistry as a drug discovery tool. Medicinal chemistry is constantly being challenged to develop efficient methodologies for the synthesis of compounds for drug discovery. Following completion of the Human Genome project, the cloning and expression of new proteins will proceed at an accelerated rate. In the absence of biochemical knowledge of the target protein there is a growing interest in techniques that expand the structural and biological diversity of compound libraries. Dynamic combinatorial chemistry is an innovative technology with the capacity for supporting the shift from focussed to diverse compound libraries. This application seeks funding to refine dynamic combinatorial chemistry into an effective drug discovery tool.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE150100203
Funder
Australian Research Council
Funding Amount
$860,000.00
Summary
South Australian High Throughput Screening Facility. High throughput screening facility: The project aims to establish a high throughput screening facility (including a confocal cell imager and surface plasmon resonance facility) to provide researchers with access to equipment that will enable cultured cells to be screened with large libraries of chemicals or nucleic acids (over-expression, RNA interference, microRNAs, long non-coding RNAs). Cellular responses can be monitored by biochemical ass ....South Australian High Throughput Screening Facility. High throughput screening facility: The project aims to establish a high throughput screening facility (including a confocal cell imager and surface plasmon resonance facility) to provide researchers with access to equipment that will enable cultured cells to be screened with large libraries of chemicals or nucleic acids (over-expression, RNA interference, microRNAs, long non-coding RNAs). Cellular responses can be monitored by biochemical assays or detailed imaging. These screens will enable dissection of biological pathways and discovery of genes that regulate fundamental biological processes. Models will include microbial, plant and mammalian cells. The facility will also study inter-molecular interactions. Fragment-based lead discovery screens will generate novel reagents for studying protein and membrane biology.Read moreRead less
A Gas Phase Study of Macromolecular Biological Complexes. Following the completion of the human genome project, increased attention has focussed on the elucidation of structure and function of biopolymers in cells. The project aims to use electrospray ionisation mass spectrometry (a rapidly developing analytical technique) to detail the processes governing the formation of macromolecular complexes (DNA-protein and DNA-metal-protein) in the gas phase. We aim to explore the relevance of gas pha ....A Gas Phase Study of Macromolecular Biological Complexes. Following the completion of the human genome project, increased attention has focussed on the elucidation of structure and function of biopolymers in cells. The project aims to use electrospray ionisation mass spectrometry (a rapidly developing analytical technique) to detail the processes governing the formation of macromolecular complexes (DNA-protein and DNA-metal-protein) in the gas phase. We aim to explore the relevance of gas phase studies of these large macromolecular complexes to interactions between biopolymers in solution and cells. Ultimately, this will aid in the development of improved therapeutics tha t act on DNA and/or DNA-binding proteins and provide new information on biological processes such as replicaton.Read moreRead less
Allosteric Enhancers: Leads for the Therapy of Cardiovascular Disease. Cardiovascular disease (CVD - heart, stroke and blood vessel disease) kills more people each year than cancer, AIDS and traffic accidents combined. Coronary heart disease (CHD), followed by stroke, is the largest single cause of death in Australia. Allosteric enhancers are particularly attractive drug targets for the prevention of CVD due to their ability to limit injury associated with ischaemic tissue trauma selectively ....Allosteric Enhancers: Leads for the Therapy of Cardiovascular Disease. Cardiovascular disease (CVD - heart, stroke and blood vessel disease) kills more people each year than cancer, AIDS and traffic accidents combined. Coronary heart disease (CHD), followed by stroke, is the largest single cause of death in Australia. Allosteric enhancers are particularly attractive drug targets for the prevention of CVD due to their ability to limit injury associated with ischaemic tissue trauma selectively in tissues where adenosine is elevated. Whilst the development of drugs that protect against heart attack and stroke is a difficult and long term objective, any advances toward this goal would clearly be of great benefit to the community.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