New Frontiers in Molybdenum Chemistry: Electronic Structure and Molybdoenzyme Function. Molybdenum enzymes play key roles in biology and environmental, biogeochemical and meteorological processes. This international, multidisciplinary project will employ advanced synthetic, instrumental and theoretical techniques to establish the link between electronic structures and molybdenum enzyme behaviour and function. The insights gained will inform the continuing development of agricultural, veterinary ....New Frontiers in Molybdenum Chemistry: Electronic Structure and Molybdoenzyme Function. Molybdenum enzymes play key roles in biology and environmental, biogeochemical and meteorological processes. This international, multidisciplinary project will employ advanced synthetic, instrumental and theoretical techniques to establish the link between electronic structures and molybdenum enzyme behaviour and function. The insights gained will inform the continuing development of agricultural, veterinary and medical treatments for diseases associated with enzyme dysfunction; these outcomes would be of enormous economic and societal benefit to Australia. The training of skilled scientists, access to advanced overseas facilities, and international recognition of Australian research, are important immediate benefits of the project.Read moreRead less
Chemistry of the Transport of Nutrient Copper in Biological Cells. Nutrient trace metals such as copper are needed for enzymes by living organisms but are toxic in excess. Defects in copper metabolism cause Menkes and Wilson diseases in humans and there are direct connections to neurodegenerative diseases (eg, Alzheimer, Parkinson, Creutzfeldt-Jakob, motor neuron diseases). It is crucial to understand how healthy cells control toxic but essential copper so that enlightened intervention is possib ....Chemistry of the Transport of Nutrient Copper in Biological Cells. Nutrient trace metals such as copper are needed for enzymes by living organisms but are toxic in excess. Defects in copper metabolism cause Menkes and Wilson diseases in humans and there are direct connections to neurodegenerative diseases (eg, Alzheimer, Parkinson, Creutzfeldt-Jakob, motor neuron diseases). It is crucial to understand how healthy cells control toxic but essential copper so that enlightened intervention is possible when disturbances of copper metabolism become pathological. The chemistry of key molecules will be studied to reveal their essential properties and thereby to understand the molecular basis of the copper-linked diseases.Read moreRead less
Molecular Characterisation of Metal Transport Proteins. The trace metals are essential to life. The secrets of their catalytic and structural roles are under intensive scrutiny. The molecular mechanisms which regulate concentrations of nutrient metals in biological cells remain poorly understood. Errors in metal metabolism cause disease. For example, defects in copper metabolism cause Menkes and Wilson diseases in humans and there are connections of copper and zinc to neuro-degenerative disea ....Molecular Characterisation of Metal Transport Proteins. The trace metals are essential to life. The secrets of their catalytic and structural roles are under intensive scrutiny. The molecular mechanisms which regulate concentrations of nutrient metals in biological cells remain poorly understood. Errors in metal metabolism cause disease. For example, defects in copper metabolism cause Menkes and Wilson diseases in humans and there are connections of copper and zinc to neuro-degenerative diseases such as Alzheimer and Creutzfeldt-Jakob (mad cow). This project will study the chemistry of metabolic pathways responsible for import of nutrient copper and other metals into biological cells.Read moreRead less
Copper Radiopharmaceuticals for Molecular Imaging of Alzheimer's Disease. The expected outcome of this research is to develop molecular agents to allow non-invasive diagnostic imaging of senile plaques associated with the onset of Alzheimer's disease. This will contribute to a better understanding of the disease, assist in early diagnosis and help assess new intervention strategies. Alzheimer's disease is the most common form of dementia and affects over 160,000 Australians. The imaging agent ma ....Copper Radiopharmaceuticals for Molecular Imaging of Alzheimer's Disease. The expected outcome of this research is to develop molecular agents to allow non-invasive diagnostic imaging of senile plaques associated with the onset of Alzheimer's disease. This will contribute to a better understanding of the disease, assist in early diagnosis and help assess new intervention strategies. Alzheimer's disease is the most common form of dementia and affects over 160,000 Australians. The imaging agent market is a niche biotechnology industry in which Australia already has an international presence. The proposed research will lead to innovations to ensure Australia remains internationally competitive in this area. This research has potential social and economic benefits for the nation.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
Design, Evaluation, and Selection of Novel Pt(IV) Complexes as Anticancer Agents. Platinum anticancer drugs are arguably the most widely used anticancer agents in the world but serious problems remain with toxicity and resistance. Platinum(IV) compounds have numerous advantages in terms of stability and thereby, lower toxicity. In this project we will exploit these advantages along with others that we have discovered recently and our understanding of the chemistry and biology of platinum(IV) to ....Design, Evaluation, and Selection of Novel Pt(IV) Complexes as Anticancer Agents. Platinum anticancer drugs are arguably the most widely used anticancer agents in the world but serious problems remain with toxicity and resistance. Platinum(IV) compounds have numerous advantages in terms of stability and thereby, lower toxicity. In this project we will exploit these advantages along with others that we have discovered recently and our understanding of the chemistry and biology of platinum(IV) to develop novel platinum(IV) compounds to the point where the industry partner can commercialise them.Read moreRead less
Heavy Metal Chemistry Goes Nuclear: Radioactive Rhenium and Terbium Agents. This project aims to make fundamental advances in the basic knowledge of the bioinorganic chemistry of radioactive metals that have the potential to be used in the future as radioactive drugs. Technological advances in the production of radioactive isotopes of rhenium and terbium have increased the feasibility of using these radionuclides as radioactive drugs, but their use requires new basic knowledge in their fundament ....Heavy Metal Chemistry Goes Nuclear: Radioactive Rhenium and Terbium Agents. This project aims to make fundamental advances in the basic knowledge of the bioinorganic chemistry of radioactive metals that have the potential to be used in the future as radioactive drugs. Technological advances in the production of radioactive isotopes of rhenium and terbium have increased the feasibility of using these radionuclides as radioactive drugs, but their use requires new basic knowledge in their fundamental coordination chemistry. This project will develop new ways to synthesise radioactive rhenium and terbium complexes. The outcomes of this project will be an improved understanding of the coordination chemistry rhenium and terbium which is required to inform their future translation to new radiopharmaceuticals.Read moreRead less