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
Pushing the Boundaries of Multi-modal Biospectroscopic Microscopies. In order to understand the fundamentals of life processes, diseases, and their treatments, it is essential to probe fundamental changes in molecular processes in cells, tissues and whole organisms. Much of our understanding of these processes has involved the introduction of chemical probes for biospectroscopy, but these have inherent problems because the probe can often change the biochemistry that is being probed. This projec ....Pushing the Boundaries of Multi-modal Biospectroscopic Microscopies. In order to understand the fundamentals of life processes, diseases, and their treatments, it is essential to probe fundamental changes in molecular processes in cells, tissues and whole organisms. Much of our understanding of these processes has involved the introduction of chemical probes for biospectroscopy, but these have inherent problems because the probe can often change the biochemistry that is being probed. This project will push the boundaries of a variety of micro and nano "probe-free" microscopies to provide fundamental insights into these life processes, which could ultimately lead to improvements in the diagnosis, prevention and treatment of diseases.Read moreRead less
Bioinorganic chemistry between immune cell and pathogen. This project aims to investigate the bioinorganic chemistry that occurs when immune system cells encounter pathogens and they try to kill one another, or in the case of a pathogen, to also modify the genetics of the mammalian cell to enable its intracellular survival. Pathogenic bacteria and fungi accumulate chromium (Cr) in their membranes and it was recently discovered that Cr is likely to be an important virulence factor. Similarly, H ....Bioinorganic chemistry between immune cell and pathogen. This project aims to investigate the bioinorganic chemistry that occurs when immune system cells encounter pathogens and they try to kill one another, or in the case of a pathogen, to also modify the genetics of the mammalian cell to enable its intracellular survival. Pathogenic bacteria and fungi accumulate chromium (Cr) in their membranes and it was recently discovered that Cr is likely to be an important virulence factor. Similarly, Hyperaccummulation of Nickel (Ni) is also involved in virulence. The project will investigate the roles of Cr and Ni in virulence using advanced spectroscopic imaging and biochemical techniques. These insights will provide new knowledge on the innate immune system and may lead to more efficacious treatments for serious infections.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
DNA Nanoshuttles: A New Class of DNA-Binding Molecules. The interaction of molecules with DNA, the molecule that controls genetic information, is fundamental to drug design, diagnosis of disease and the environment. DNA-nanoshuttles are ring-shaped molecules that thread onto DNA and shuttle from one end to the other. This threading interaction is without precedent and hence DNA-nanoshuttles have significant potential applications in all areas of medicine, biotechnology and nanotechnology that in ....DNA Nanoshuttles: A New Class of DNA-Binding Molecules. The interaction of molecules with DNA, the molecule that controls genetic information, is fundamental to drug design, diagnosis of disease and the environment. DNA-nanoshuttles are ring-shaped molecules that thread onto DNA and shuttle from one end to the other. This threading interaction is without precedent and hence DNA-nanoshuttles have significant potential applications in all areas of medicine, biotechnology and nanotechnology that involve DNA interactions. This research may lead to the design of new 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
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
Mechanistic Studies on Biologically Active Iron Chelators. The need for orally effective drugs as alternatives to invasive treatment regimens such as subcutaneous infusion is an ongoing concern in health care. This is particularly true in people suffering iron overload. In many cases this condition is present at birth and thus the administration of vital iron chelation therapy via the oral route is a much preferred option. We have unearthed a novel series of candidates for iron chelation therapy ....Mechanistic Studies on Biologically Active Iron Chelators. The need for orally effective drugs as alternatives to invasive treatment regimens such as subcutaneous infusion is an ongoing concern in health care. This is particularly true in people suffering iron overload. In many cases this condition is present at birth and thus the administration of vital iron chelation therapy via the oral route is a much preferred option. We have unearthed a novel series of candidates for iron chelation therapy (the pyridine-2-carboxaldehyde isonicotinoyl hydrazone [PCIH] analogues) which show oral activity. These chelators undergo some interesting iron catalysed oxidation chemistry and it is vital that the mechanism of this reaction be elucidated to determine whether it will be of biological significance upon administration of these compounds as iron chelators.Read moreRead less
Cation Ordering - A Strategy to Prepare Multiferroic Oxides. This project will produce new families of functional metal oxides with technologically relevant properties, especially multiferroic behavior. Such materials are highly sort-after in the rapidly emerging field of spintronics. Through comprehensive experimental studies of a number of such materials this project will enhance the ability of industry to develop new and improved materials.
A new metalloprotein-inspired methodology for energy-efficient chemical reduction. Chemical reduction, a core process in chemistry and industry, is carried out on an enormous scale using present-day technology that is extremely energy wasteful and irreversibly consumes resources. This project aims to provide a new sustainable methodology for chemical reduction using sophisticated bio-inspired metal (electro) catalysts.
Renewable solar hydrogen generated from waste streams. Sunlight is the largest available carbon-neutral energy source, with enough energy striking the planet in one hour to satisfy our current requirements for about a year. With the novel catalysts designed in this project, we will use this energy to simultaneously generate hydrogen and destroy organic pollutants by oxidation.