The roles of metal ions in glucose metabolism and the treatment of diabetes. Metal supplements, such as chromium and vanadium are consumed widely for their purported fat reduction and anti-diabetic activities. However, much is still to be learnt about the efficacy and safety of such metal ions when they are taken in supplements and whether they have an essential role in the prevention of diabetes or, in some instances, are a risk factor for cancer. The research will provide an understanding of ....The roles of metal ions in glucose metabolism and the treatment of diabetes. Metal supplements, such as chromium and vanadium are consumed widely for their purported fat reduction and anti-diabetic activities. However, much is still to be learnt about the efficacy and safety of such metal ions when they are taken in supplements and whether they have an essential role in the prevention of diabetes or, in some instances, are a risk factor for cancer. The research will provide an understanding of how these metal complexes exert their anti-diabetic effects and how they can be made safer and/or more efficacious for the treatment of type 2 diabetes, which is a rapidly expanding epidemic in developed countries. Read moreRead less
Design and Mechanistic Studies of Metal-Based Anti-Diabetic Drugs. Metal supplements, such as chromium and vanadium, are consumed widely for their purported fat reduction and anti-diabetic activities. However, much is still to be learnt about the efficacy and safety of such metal ions and whether they have an essential role in the prevention of diabetes or, in some instances, are a risk factor for cancer. The research will provide a fundamental understanding of how these metal complexes exert th ....Design and Mechanistic Studies of Metal-Based Anti-Diabetic Drugs. Metal supplements, such as chromium and vanadium, are consumed widely for their purported fat reduction and anti-diabetic activities. However, much is still to be learnt about the efficacy and safety of such metal ions and whether they have an essential role in the prevention of diabetes or, in some instances, are a risk factor for cancer. The research will provide a fundamental understanding of how these metal complexes exert their anti-diabetic effects and how they can be made safer and/or more efficacious for the treatment of type 2 diabetes, which is a rapidly expanding epidemic in developed countries. 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
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
Metal complex-aminoglycoside conjugates for sequence-specific cleavage of ribonucleic acid (RNA). Ribonucleic acid (RNA) is emerging as an increasingly attractive drug target in the search for new approaches to combat diseases such as HIV/AIDS. This project will help position Australia at the forefront of research developments in the field of RNA-drug interactions, through the development of novel compounds that can cleave RNA molecules found in bacteria and retroviruses. In addition to a valuab ....Metal complex-aminoglycoside conjugates for sequence-specific cleavage of ribonucleic acid (RNA). Ribonucleic acid (RNA) is emerging as an increasingly attractive drug target in the search for new approaches to combat diseases such as HIV/AIDS. This project will help position Australia at the forefront of research developments in the field of RNA-drug interactions, through the development of novel compounds that can cleave RNA molecules found in bacteria and retroviruses. In addition to a valuable body of knowledge that will assist in the future development of new drugs, this project will provide high quality multi-disciplinary training for young scientists keenly sought by emerging medical and biotechnological industries, research organisations and universities.Read moreRead less
Nanosized peptide nucleic acid - metal complex hybrids as catalysts for the cleavage of phosphate ester bonds in biological molecules. The information from Human Genome Project is being used to generate molecules with a variety of therapeutic and diagnostic applications. The capability to design, synthesise and manipulate functional molecules that mimic biological processes will underpin many emerging applications. In this project, macrocyclic metal complexes that catalyse the cleavage of phosph ....Nanosized peptide nucleic acid - metal complex hybrids as catalysts for the cleavage of phosphate ester bonds in biological molecules. The information from Human Genome Project is being used to generate molecules with a variety of therapeutic and diagnostic applications. The capability to design, synthesise and manipulate functional molecules that mimic biological processes will underpin many emerging applications. In this project, macrocyclic metal complexes that catalyse the cleavage of phosphate ester bonds in biological molecules will be developed. Active complexes will be incorporated into nanosized peptide nucleic acid (PNA) - metal complex hybrids and applied as artificial enzymes in the sequence specific cleavage of RNA and DNA. Novel applications of these ?artificial enzymes? in biotechnology are anticipated.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
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