Targeting Fungal Phospholipid Metabolism For Antifungal Drug Discovery
Funder
National Health and Medical Research Council
Funding Amount
$828,557.00
Summary
Invasive fungal infections are a serious and escalating health problem. They cause severe disease with a high death rate and are very costly to the health system. New antifungal drugs with novel properties are needed now because there are problems with current drugs. This project aims to develop potent new antifungal drugs that are effective in many fungal diseases and are well-tolerated.
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
Development of metal probes for the selective recognition of DNA. Transition metal complexes with large aromatic ligands have recently been shown to bind DNA by intercalation. However, controversy continues over their base sequence and groove selectivity. We will synthesise a range of chiral metal complexes and screen these against combinatorial oligonucleotide libraries to determine their base sequence selectivity. The information obtained will help us design better intercalators that can be us ....Development of metal probes for the selective recognition of DNA. Transition metal complexes with large aromatic ligands have recently been shown to bind DNA by intercalation. However, controversy continues over their base sequence and groove selectivity. We will synthesise a range of chiral metal complexes and screen these against combinatorial oligonucleotide libraries to determine their base sequence selectivity. The information obtained will help us design better intercalators that can be used as sensitive molecular probes and may find application as antitumour drugs. Binding interaction between the complex and DNA will be studied by NMR spectroscopy.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
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
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
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
Smart bio-mimetic self-assembled gels for biomedical applications. Advanced materials that can be used to deliver drugs, repair scars and damaged tissue are the holy grail of regenerative medicine. Recently, a class of materials called self-assembled gels have shown enormous potential in this regard. Self-assembled gels have already demonstrated their use in drug delivery and are showing great promise in the treatment of spinal injuries. This project will create an even smarter version of these ....Smart bio-mimetic self-assembled gels for biomedical applications. Advanced materials that can be used to deliver drugs, repair scars and damaged tissue are the holy grail of regenerative medicine. Recently, a class of materials called self-assembled gels have shown enormous potential in this regard. Self-assembled gels have already demonstrated their use in drug delivery and are showing great promise in the treatment of spinal injuries. This project will create an even smarter version of these gels with biological activity, especially targeting cancer and suppressing tumour growth after surgery. Our approach will help to ensure that Australians can take a leading role in this highly exciting new area of biomedical research.Read moreRead less
The discovery and validation of novel drug classes against parasites with the potential for major economic impacts. This project will develop a quality scientific and technological program in national priority areas, leading to a strong basic research, new concepts and the enhanced international collaborative links; strengthen links between basic and applied research, and academia and industry; develop excellence via pan-Australian collaborations, resulting in a more efficient use of resources i ....The discovery and validation of novel drug classes against parasites with the potential for major economic impacts. This project will develop a quality scientific and technological program in national priority areas, leading to a strong basic research, new concepts and the enhanced international collaborative links; strengthen links between basic and applied research, and academia and industry; develop excellence via pan-Australian collaborations, resulting in a more efficient use of resources in a national and international context; enhance the skills-base in biology, biotechnology and chemistry; increase global visibility with increased investment in Australian science; improve animal welfare and production via improved control of infectious diseases; producing commercial products with benefits to agricultural producers in regional & rural communities.Read moreRead less