Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100109
Funder
Australian Research Council
Funding Amount
$530,000.00
Summary
Small molecule X-ray molecular structure elucidation facility. X-ray diffraction plays a key role in identification and molecular characterisation. X-ray techniques are the single most widely used analytical resource in structure determination and provide invaluable information for scientists working in the fields of synthesis, nanotechnology, polymer chemistry, and protein chemistry, amongst many others. The facility brings together a multidisciplinary team of scientists and provides state-of-t ....Small molecule X-ray molecular structure elucidation facility. X-ray diffraction plays a key role in identification and molecular characterisation. X-ray techniques are the single most widely used analytical resource in structure determination and provide invaluable information for scientists working in the fields of synthesis, nanotechnology, polymer chemistry, and protein chemistry, amongst many others. The facility brings together a multidisciplinary team of scientists and provides state-of-the-art research and training facilities for these techniques.Read moreRead less
Enzyme-Mediated Machining of Chelators to Bind and Recover Valuable Metals. Metals are critical components of electronic devices and electrical products. Rapid disposal cycles create a major problem in managing e-waste metals and identifies an opportunity in the circular economy for recovery and re-use. Organic compounds that bind metal ions (chelators) are useful but could be improved to select a target metal from a mixture. This project aims to dissect a method used by bacteria to biosynthesiz ....Enzyme-Mediated Machining of Chelators to Bind and Recover Valuable Metals. Metals are critical components of electronic devices and electrical products. Rapid disposal cycles create a major problem in managing e-waste metals and identifies an opportunity in the circular economy for recovery and re-use. Organic compounds that bind metal ions (chelators) are useful but could be improved to select a target metal from a mixture. This project aims to dissect a method used by bacteria to biosynthesize chelators and hijack this to bioengineer new classes of chelators. Outcomes include new chelators and advanced knowledge of metal selectivity, with potential environmental and economic benefits arising from recovery of valuable metals. The project will benefit chemical biology research training for real-world applications.Read moreRead less
Development of New Materials Based on Multinuclear Ruthenium Complexes. The program aims to design new materials for use in applications such as catalysis and light-activated devices (including light harvesting or solar energy conversion), for the detection and analysis of specific small molecules and anions of particular interest, and to provide an insight to the operation of biological systems such as metal-containing enzymes. The particular molecules will also be investigated for the developm ....Development of New Materials Based on Multinuclear Ruthenium Complexes. The program aims to design new materials for use in applications such as catalysis and light-activated devices (including light harvesting or solar energy conversion), for the detection and analysis of specific small molecules and anions of particular interest, and to provide an insight to the operation of biological systems such as metal-containing enzymes. The particular molecules will also be investigated for the development of a new type of therapeutic agent for the treatment of a range of diseases, with a particular interest in this work on a drug for the treatment of HIV-AIDS. 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
Formation, structure and chemistry of non-covalent complexes of biomolecules via mass spectrometry. The studies proposed address fundamental issues which are essential to developments in biotechnology and related industries and of implication for human health and disease, with special attention to mechanisms of Deoxyribonucleic acid (DNA) damage, for example through Ultraviolet (UV) A and B. This has a special resonance for our sunburnt nation. The work, using world class Australian Research Cou ....Formation, structure and chemistry of non-covalent complexes of biomolecules via mass spectrometry. The studies proposed address fundamental issues which are essential to developments in biotechnology and related industries and of implication for human health and disease, with special attention to mechanisms of Deoxyribonucleic acid (DNA) damage, for example through Ultraviolet (UV) A and B. This has a special resonance for our sunburnt nation. The work, using world class Australian Research Council funded instrumentation, will carry out breakthrough science, exploiting and enhancing existing national strength in biological science with a strong interdisciplinary element. This project will also maintain and enhance Australia's international research profile through its novelty and new overseas collaborations. The project will equip talented young scientists with a spectrum of skills.Read moreRead less
Gas phase studies of the interactions of electrons with peptide ions: structure assignment and fundamentals. Electron-induced reactions are fundamental to a wide range of processes that underlie many areas of science and technology, ranging from planetary atmospheres, industrial plasmas to living tissues. Since ionizing radiation is believed to be a major cause of damage to living cells, understanding electron interactions with biological molecules is essential to predict the consequences of ex ....Gas phase studies of the interactions of electrons with peptide ions: structure assignment and fundamentals. Electron-induced reactions are fundamental to a wide range of processes that underlie many areas of science and technology, ranging from planetary atmospheres, industrial plasmas to living tissues. Since ionizing radiation is believed to be a major cause of damage to living cells, understanding electron interactions with biological molecules is essential to predict the consequences of exposure. Structure determination of biomolecules is at the heart of identifying, diagnosing and potentially developing treatments for diseases, and thus another important reason for studying these interactions is the potential to develop new mass spectrometry based analytical methods.Read moreRead less
Gas Phase Reactivity of Charged Peptide and DNA Radicals: Fundamentals and Applications. Radicals derived from the "molecules of life", proteins and DNA, play both beneficial (e.g. enzyme catalysis) and deleterious roles (e.g. protein and DNA damage associated with disease). Two electrospray ionisation mass spectrometry approaches have been discovered to generate charged radicals of related models systems (e.g. peptides and nucleobases). The gas phase chemistry of these species is a largely unch ....Gas Phase Reactivity of Charged Peptide and DNA Radicals: Fundamentals and Applications. Radicals derived from the "molecules of life", proteins and DNA, play both beneficial (e.g. enzyme catalysis) and deleterious roles (e.g. protein and DNA damage associated with disease). Two electrospray ionisation mass spectrometry approaches have been discovered to generate charged radicals of related models systems (e.g. peptides and nucleobases). The gas phase chemistry of these species is a largely unchartered area! We will examine the fundamental chemistry (unimolecular and bimolecular reactions) of these systems and build upon some exciting preliminary results which suggest potential applications (e.g. as a proteomics tool to sequence and distinguish between leucine and isoleucine residues in peptides).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