Synthesis and Applications of Antifreeze Proteins and Glycoproteins. Many cells are damaged when they are chilled below body temperatures thus limiting shelf-life for applications. For example, storage of human blood platelets is limited to 5 days at 22 degrees. This research will produce molecules that can be used in the fields of agriculture (in vitro fertilization techniques, development of improved blood lines), aquaculture and human reproductive technologies, where ice crystal growth and fr ....Synthesis and Applications of Antifreeze Proteins and Glycoproteins. Many cells are damaged when they are chilled below body temperatures thus limiting shelf-life for applications. For example, storage of human blood platelets is limited to 5 days at 22 degrees. This research will produce molecules that can be used in the fields of agriculture (in vitro fertilization techniques, development of improved blood lines), aquaculture and human reproductive technologies, where ice crystal growth and freezing are damaging. This outcome will be achieved by the synthesis of molecules that mimic natural products that allow fish to survive in the icy Arctic and Arctic Oceans and study how they are able to protect cells and tissues from damage in these extreme environments.Read moreRead less
Escaping Bio-Assay Guided Isolation: Nature's Tools for Chemical Biology. The project aims to transform the approach to identify novel biologically active compounds that occur in nature. For decades, natural product chemistry has centred on bio-assay guided isolation, but it has become increasingly difficult to isolate novel compounds. While de-replication strategies detect the presence of known compounds using databases, more impact would be achieved by directly detecting novel compounds. Nucle ....Escaping Bio-Assay Guided Isolation: Nature's Tools for Chemical Biology. The project aims to transform the approach to identify novel biologically active compounds that occur in nature. For decades, natural product chemistry has centred on bio-assay guided isolation, but it has become increasingly difficult to isolate novel compounds. While de-replication strategies detect the presence of known compounds using databases, more impact would be achieved by directly detecting novel compounds. Nuclear magnetic resonance (NMR) spectroscopy detects every molecule that has a proton and is quantitative. This project plans to develop a NMR technique to escape bio-assay guided isolation by analysing a fraction library. Biotechnology innovation is dependent on novel compounds to provide new products. Replacing ‘grind and find’ with a technique that never lies would be transformational.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
Nicotinic acetylcholine receptors as targets in inflammatory and neurodegenerative processes. The national/community benefits that are expected to arise from this research are economic and social in nature. The novel approach employed in this project to identify inflammatory pathways and regulation has the potential to provide information that is critical in the design of novel peptide/protein based drugs. With blockbuster protein-based drugs having sales in excess of $10 billion per annum this ....Nicotinic acetylcholine receptors as targets in inflammatory and neurodegenerative processes. The national/community benefits that are expected to arise from this research are economic and social in nature. The novel approach employed in this project to identify inflammatory pathways and regulation has the potential to provide information that is critical in the design of novel peptide/protein based drugs. With blockbuster protein-based drugs having sales in excess of $10 billion per annum this proposal has the potential for very significant economic benefits for Australia. Furthermore, novel therapeutic agents for inflammatory diseases would have social benefits for Australia by decreasing the number of individuals affected and thereby reducing the physical and emotional stress associated with inflammatory diseases. Read moreRead less
Novel Sodium Ion Channel Modulators From Australian Cephalopods. Many Australian cephalopods (octopuses, squids, cuttlefishes and nautiluses) use potent toxins to rapidly paralyse diverse prey and defend against predators. These toxins act by the efficient blocking of ion channels critical to the transmission of nerve impulses. Knowledge of these toxins can lead to safer and better drugs for the relief of chronic pain.
Towards an influenza virus glycan interaction map (Glycointeractome). This project will use nuclear magnetic resonance (NMR) spectroscopy to map carbohydrate interaction used by the virus to cause infection and spread. This information will provide new direction in anti-influenza drug discovery.
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
To gain insight into the molecular mechanisms involved in antibiotic resistance shown by Gram-negative bacteria. Bacterial infections can strike anyone and usually the body's immune system, which is designed to fight infection, defeats the invading bacteria. Sometimes however, the burden of infection proves too great, so these infections can prove fatal. For 50 years, we have relied on antibiotics to successfully treat the majority of common bacterial infections. As a result, emphasis must be pl ....To gain insight into the molecular mechanisms involved in antibiotic resistance shown by Gram-negative bacteria. Bacterial infections can strike anyone and usually the body's immune system, which is designed to fight infection, defeats the invading bacteria. Sometimes however, the burden of infection proves too great, so these infections can prove fatal. For 50 years, we have relied on antibiotics to successfully treat the majority of common bacterial infections. As a result, emphasis must be placed on the disquieting reality whilst enjoy the use of antibiotics, an inescapable cost is the development of bacterial resistance. The increasing prevalence of bacterial tolerance against beta-lactams is a problem and as a result is a most pressing health issue. Read moreRead less
Experimental Charge Density Studies of Hydrogen Bonding. Hydrogen bonds, vital to all biological systems, exhibit extreme variation in chemical properties. Experimental analysis of hydrogen bonds, independent from previous theories and hypotheses, by using an expansion of current high resolution, ultra-low temperature X-ray crystallography is now possible. This allows experimental observation of electronic and electrostatic properties of previously unstudied hydrogen bonds, including weak hydrog ....Experimental Charge Density Studies of Hydrogen Bonding. Hydrogen bonds, vital to all biological systems, exhibit extreme variation in chemical properties. Experimental analysis of hydrogen bonds, independent from previous theories and hypotheses, by using an expansion of current high resolution, ultra-low temperature X-ray crystallography is now possible. This allows experimental observation of electronic and electrostatic properties of previously unstudied hydrogen bonds, including weak hydrogen bonds and those involving metal atoms. Comparison of experimental observations with predictions from high-level theoretical calculations and finally incorporation of these parameters into a prototype force field for computational chemistry will allow better predictions to be made in a range of areas including medicinal and materials chemistry.Read moreRead less
Targeting DNA with Dynamic Combinatorial Chemistry. The interaction of molecules with DNA, the molecule that controls genetic information, is fundamental to drug design, diagnosis of disease and the environment. Chemists usually synthesise these molecules in the laboratory. We will use an innovative new approach to producing molecules that interact with DNA, that as fast and efficient and mirrors the processes used by Nature to make natural products. This research may lead to the design of new ....Targeting DNA with Dynamic Combinatorial Chemistry. The interaction of molecules with DNA, the molecule that controls genetic information, is fundamental to drug design, diagnosis of disease and the environment. Chemists usually synthesise these molecules in the laboratory. We will use an innovative new approach to producing molecules that interact with DNA, that as fast and efficient and mirrors the processes used by Nature to make natural products. This research may lead to the design of new therapeutics, diagnostics and applications that will benefit the Australian community, and will provide excellent training of researchers in skills required for employment in the biotechnology and pharmaceutical fields.Read moreRead less