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Special Research Initiatives - Grant ID: SR0354474
Funder
Australian Research Council
Funding Amount
$30,000.00
Summary
Metals in Medicine. Metal-based drugs account for several billion dollars of pharmaceutical sales worldwide, but proportionally much less research and development has focussed on this area than organic drugs. Australia has played a pivotal role in the early development of metal-based pharmaceuticals, which remains a research strength. The dual aims of the initiative are to provide a network for a vibrant industry based around metals in medicine and to improve the health of Australians. The ini ....Metals in Medicine. Metal-based drugs account for several billion dollars of pharmaceutical sales worldwide, but proportionally much less research and development has focussed on this area than organic drugs. Australia has played a pivotal role in the early development of metal-based pharmaceuticals, which remains a research strength. The dual aims of the initiative are to provide a network for a vibrant industry based around metals in medicine and to improve the health of Australians. The initiative will foster national and international cross-disciplinary collaborations to address the impediments holding back Australia's potential to take full advantage of our research strength in metals in medicine.Read moreRead less
Dinuclear Ruthenium Complexes as Sequence- and Structure-Selective Binding Agents for DNA. Studies of the interaction of mononuclear metal complexes with DNA have greatly increased our understanding of the ways that small molecules recognise particular sites on DNA. However, in order to design drugs that target specific genes, and hence be potentially capable of controlling gene expression, it is necessary to study the binding of metal complexes that can associate with larger segments of DNA. ....Dinuclear Ruthenium Complexes as Sequence- and Structure-Selective Binding Agents for DNA. Studies of the interaction of mononuclear metal complexes with DNA have greatly increased our understanding of the ways that small molecules recognise particular sites on DNA. However, in order to design drugs that target specific genes, and hence be potentially capable of controlling gene expression, it is necessary to study the binding of metal complexes that can associate with larger segments of DNA. Using the combined expertise of the applicants, it is proposed to stereospecifically synthesise dinuclear complexes and study their DNA binding. This will greatly assist in the development of drugs that can selectively target genes and altered DNA.Read moreRead less
The fate of dietary selenium in vivo; a direct approach to linking chemical form with biological activity. Dietary selenium supplementation has great potential as a preventative treatment for a range of human health conditions, including cancer, that widely affect the Australian population. However, the adverse effects of such treatments are not fully recognised. This project will increase our knowledge of how selenium compounds are stored and utilised in the body and relate the information to c ....The fate of dietary selenium in vivo; a direct approach to linking chemical form with biological activity. Dietary selenium supplementation has great potential as a preventative treatment for a range of human health conditions, including cancer, that widely affect the Australian population. However, the adverse effects of such treatments are not fully recognised. This project will increase our knowledge of how selenium compounds are stored and utilised in the body and relate the information to clinical observations regarding dietary intake of selenium and other compounds. The new understanding generated will delineate the conditions for safe intake, so that the beneficial effects associated with selenium supplementation may be harnessed more effectively.Read moreRead less
Microprobe and Nanoprobe Studies on Intracellular Disease Processes and Their Treatment. Breakthrough microprobe and nanoprobe technologies, involving X-ray, visible and infrared light can focus into different components of mammalian cells in order to interrogate the biochemistry that is occurring therein. Each of the different wavelengths of light provides complementary biochemical information that enables a deeper understanding of changes in cells that occur as a function of drug treatments an ....Microprobe and Nanoprobe Studies on Intracellular Disease Processes and Their Treatment. Breakthrough microprobe and nanoprobe technologies, involving X-ray, visible and infrared light can focus into different components of mammalian cells in order to interrogate the biochemistry that is occurring therein. Each of the different wavelengths of light provides complementary biochemical information that enables a deeper understanding of changes in cells that occur as a function of drug treatments and disease processes. This will provide unprecedented information as to where drugs go and how they are transformed inside cells that, in turn, may revolutionalise the way in which new drugs are designed that have higher specificity and fewer side effects.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
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
Metalloproteins and metalloenzymes. Most of the chemical reactions and physical movements in living systems are carried out by proteins. The information for producing proteins from amino acids is stored in the genes, but many biological processes depend on additional atoms or molecules ('cofactors') that are added to a protein after it is assembled. For example, more than 30% of all proteins contain metal atoms which are essential for their function. We are studying the structures of such meta ....Metalloproteins and metalloenzymes. Most of the chemical reactions and physical movements in living systems are carried out by proteins. The information for producing proteins from amino acids is stored in the genes, but many biological processes depend on additional atoms or molecules ('cofactors') that are added to a protein after it is assembled. For example, more than 30% of all proteins contain metal atoms which are essential for their function. We are studying the structures of such metalloproteins and metalloenzymes so that we can better understand their activities with long term aims of creating new molecules for biotechnology and/or drugs.Read moreRead less
Probing and Developing Hypoxia-Selective Anti-Cancer Agents. The development of compounds that are effective in the treatment of cancer and are less toxic than existing drugs depends on the selective targeting of tumours. Solid tumours have poorly oxygenated regions which represent unique chemical environments that can be targeted using selectively activated compounds. In this project we will develop the first in situ methods for monitoring the activation state in solid tumours to establish the ....Probing and Developing Hypoxia-Selective Anti-Cancer Agents. The development of compounds that are effective in the treatment of cancer and are less toxic than existing drugs depends on the selective targeting of tumours. Solid tumours have poorly oxygenated regions which represent unique chemical environments that can be targeted using selectively activated compounds. In this project we will develop the first in situ methods for monitoring the activation state in solid tumours to establish the selectivity of activation. These results will be used to tune the properties of two novel classes of selectively activated compounds and thereby develop agents able to treat the most problematic of cancers.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0560680
Funder
Australian Research Council
Funding Amount
$901,862.00
Summary
Vibrational Spectroscopy Microprobe/FESEM/AFM Imaging of Cells, Tissues and Materials. State-of-the-art vibrational mapping and imaging equipment (integrated with a field-emission scanning electron microscope (FESEM) and an atomic force microscope (AFM)) will provide enabling technologies for cutting-edge research in disease diagnosis, identification of pathogens, mapping of the entry and distribution of pharmaceutics into cells, and materials research. An InVia Renishaw Raman spectrometer (sub ....Vibrational Spectroscopy Microprobe/FESEM/AFM Imaging of Cells, Tissues and Materials. State-of-the-art vibrational mapping and imaging equipment (integrated with a field-emission scanning electron microscope (FESEM) and an atomic force microscope (AFM)) will provide enabling technologies for cutting-edge research in disease diagnosis, identification of pathogens, mapping of the entry and distribution of pharmaceutics into cells, and materials research. An InVia Renishaw Raman spectrometer (sub-micron spatial positioning and micron spatial resolution) will be interfaced to an FEI Quanta FESEM for combined Raman (spectroscopic), EDS and SEM (morphological) imaging/mapping at the sub-cellular level. Complementary new-generation Raman and IR spectrometer upgrades will provide an integrated world-class equipment platform.Read moreRead less
Understanding biological nitrogen fixation: an investigation of multi-electron reduction catalysis at novel iron-sulfur clusters. A new class of iron-sulfur clusters held together by a central light atom will be prepared and their reactions thoroughly studied. These clusters are important because they will have the same structure as the iron-molybdenum cluster of the enzyme nitrogenase. This enzyme fixes atmospheric nitrogen as ammonia. It is the primary route of nitrogen entry into all living s ....Understanding biological nitrogen fixation: an investigation of multi-electron reduction catalysis at novel iron-sulfur clusters. A new class of iron-sulfur clusters held together by a central light atom will be prepared and their reactions thoroughly studied. These clusters are important because they will have the same structure as the iron-molybdenum cluster of the enzyme nitrogenase. This enzyme fixes atmospheric nitrogen as ammonia. It is the primary route of nitrogen entry into all living systems. Industrially ammonia is produced in an energy-demanding process on a vast scale. The studies will provide insights into how nitrogenase works and how to design new multi-electron reduction catalysts. The research may lead to new energy-efficient routes to ammonia and to other new alternative fuel sources. Such processes would transform Australian industry and how we live.Read moreRead less