Molecular Probes for Bio-Metals. The nutrient trace metals are essential to life. Problems with the metabolism of iron, copper and zinc are associated with neuro-degenerative diseases such as Alzheimer's, Parkinson's and CJD (Creutzfeldt-Jakob disease). This proposal will develop molecular probes for detection of iron, zinc, copper, manganese and nickel within biological cells. The work will allow examination of the molecular roles of these bio-metals in unprecedented detail and lead to a bette ....Molecular Probes for Bio-Metals. The nutrient trace metals are essential to life. Problems with the metabolism of iron, copper and zinc are associated with neuro-degenerative diseases such as Alzheimer's, Parkinson's and CJD (Creutzfeldt-Jakob disease). This proposal will develop molecular probes for detection of iron, zinc, copper, manganese and nickel within biological cells. The work will allow examination of the molecular roles of these bio-metals in unprecedented detail and lead to a better understanding of their roles in normal metabolism and in disease.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
Synthetic Molybdenum Enzymes. This project aims to produce synthetic molybdenum (Mo) enzymes, small molecules that share structural and functional attributes with the crucially important molybdopterin?Mo enzymes. These ubiquitous enzymes are essential for plant and animal health, natural cycles involving carbon, nitrogen and sulfur, and global climate control and atmospheric albedo (reflectance); consequently, they impact heavily on commerce, the environment and society. The study will provid ....Synthetic Molybdenum Enzymes. This project aims to produce synthetic molybdenum (Mo) enzymes, small molecules that share structural and functional attributes with the crucially important molybdopterin?Mo enzymes. These ubiquitous enzymes are essential for plant and animal health, natural cycles involving carbon, nitrogen and sulfur, and global climate control and atmospheric albedo (reflectance); consequently, they impact heavily on commerce, the environment and society. The study will provide urgently needed insights into the fundamental Mo?sulfur chemistry of the enzyme active sites and inform efforts to reduce the negative impacts of enzyme dysfunction and the design of new commercial catalysts.Read moreRead less
Bioinorganic Chemistry of Molybdenum. Enzymes containing the trace element molybdenum play crucial roles in plant, animal and human health, drug metabolism, environmental processes and climate. This international, multidisciplinary project will advance our understanding of the structure and function of these enzymes at the atomic level and inform strategies to reduce the impact of crop, livestock and human diseases and adverse environmental (e.g. algal blooms, leaching of toxic arsenic) and clim ....Bioinorganic Chemistry of Molybdenum. Enzymes containing the trace element molybdenum play crucial roles in plant, animal and human health, drug metabolism, environmental processes and climate. This international, multidisciplinary project will advance our understanding of the structure and function of these enzymes at the atomic level and inform strategies to reduce the impact of crop, livestock and human diseases and adverse environmental (e.g. algal blooms, leaching of toxic arsenic) and climatic events. Effective strategies would be of enormous social and economic benefit to Australia. The training of skilled scientists and access to major overseas facilities are additional benefits of the project.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
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
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
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
Gallium, Copper and Metal Fluoride Complexes Designed for Brain Imaging. This project aims to develop fundamental synthetic coordination chemistry directed toward the development of new agents for imaging brain perfusion using positron emission tomography. The research will focus on developing new coordination complexes containing positron-emitting isotopes of copper, gallium and fluorine. The goal is incorporate in these radionuclides into small molecules that can be used for the molecular imag ....Gallium, Copper and Metal Fluoride Complexes Designed for Brain Imaging. This project aims to develop fundamental synthetic coordination chemistry directed toward the development of new agents for imaging brain perfusion using positron emission tomography. The research will focus on developing new coordination complexes containing positron-emitting isotopes of copper, gallium and fluorine. The goal is incorporate in these radionuclides into small molecules that can be used for the molecular imaging of the brain. This chemistry will have the potential to replace existing technologies that rely on single-photon emission from technetium and the technique of single photon emission computed tomography.Read moreRead less