New Methods for Structural Biology in Solution. This project aims to expand the range of applications of nuclear magnetic resonance (NMR) spectroscopy in pharmaceutical research, where NMR spectroscopy is already used routinely for the identification of chemical compounds that bind to protein targets. The techniques developed aim at providing rapid and broadly applicable tools for 3D structure determinations of chemical compounds bound to their protein target, identification of protein-protein i ....New Methods for Structural Biology in Solution. This project aims to expand the range of applications of nuclear magnetic resonance (NMR) spectroscopy in pharmaceutical research, where NMR spectroscopy is already used routinely for the identification of chemical compounds that bind to protein targets. The techniques developed aim at providing rapid and broadly applicable tools for 3D structure determinations of chemical compounds bound to their protein target, identification of protein-protein interaction sites and characterization of protein motions. The limits of NMR spectroscopy will be pushed to analyse systems of significantly increased molecular weights. The project includes applications to drug targets such as the dengue virus NS2B/NS3 protease.Read moreRead less
New Methods for Structural Biology in Solution. New technologies will be developed that are sufficiently rapid and inexpensive to compete with and replace the mutagenesis experiments that biologists usually perform to identify and characterize the functionally important parts of a protein. Nuclear magnetic resonance (NMR) spectroscopy techniques in combination with various selective labelling schemes will be developed with the goal of identification and structural characterization of protein-lig ....New Methods for Structural Biology in Solution. New technologies will be developed that are sufficiently rapid and inexpensive to compete with and replace the mutagenesis experiments that biologists usually perform to identify and characterize the functionally important parts of a protein. Nuclear magnetic resonance (NMR) spectroscopy techniques in combination with various selective labelling schemes will be developed with the goal of identification and structural characterization of protein-ligand interactions at increased rates and enhanced accuracy. In addition, the three-dimensional structures of proteins and protein domains of biologically important functions and unknown fold will be determined by NMR. The project aims at techniques of direct impact in pharmaceutical industry.Read moreRead less
THE FIRST DEVELOPMENT OF MULTI-DIMENSIONAL SPECTRO-ELECTROCHEMISTRY AND ITS APPLICATION TO CRUCIAL TRANSFORMATIONS IN INORGANIC SYSTEMS. Electrolysis is a very widespread and efficient method of chemical synthesis both in industry and research. However, the link between the control voltage and the resultant current is often complicated and easily misinterpreted. To overcome this fundamental problem, we propose an optical spectro-electrochemistry instrument based on a two-dimensional CCD detectio ....THE FIRST DEVELOPMENT OF MULTI-DIMENSIONAL SPECTRO-ELECTROCHEMISTRY AND ITS APPLICATION TO CRUCIAL TRANSFORMATIONS IN INORGANIC SYSTEMS. Electrolysis is a very widespread and efficient method of chemical synthesis both in industry and research. However, the link between the control voltage and the resultant current is often complicated and easily misinterpreted. To overcome this fundamental problem, we propose an optical spectro-electrochemistry instrument based on a two-dimensional CCD detection array. This radically new approach enables simultaneous spectroscopic and spatial data mapping in the realm adjacent to an electrode surface. Important applications range from unequivocal identification of elusive molecules to monitoring metal corrosion. Our first objective is to elucidate certain crucial transformations of mono- and binuclear heavy metal complexes.Read moreRead less
Multiplexed bio-imaging mass spectrometry. This project aims to develop technology for simultaneous three-dimensional imaging of trace elements and molecules in biological tissues. This technology is an essential analytical and diagnostic advance to uncover latent mechanistic biology and will reveal subtle metabolic interactions between cells. The project will use laser ablation-inductively coupled plasma-mass spectrometry and lanthanide-conjugated probes to map the zinc metabolic pathway in the ....Multiplexed bio-imaging mass spectrometry. This project aims to develop technology for simultaneous three-dimensional imaging of trace elements and molecules in biological tissues. This technology is an essential analytical and diagnostic advance to uncover latent mechanistic biology and will reveal subtle metabolic interactions between cells. The project will use laser ablation-inductively coupled plasma-mass spectrometry and lanthanide-conjugated probes to map the zinc metabolic pathway in the ageing mouse brain. It is expected to result in a complete imaging solution for quantitative spatial determination of all important elements, co-factors, metabolites and other functional molecules to investigate metabolic pathways which current technologies find difficult or impossible to track. Ultimately this technology is expected to underpin investigations of diseases where trace metal and chemical species dysfunction is implicated.Read moreRead less
Characterization of metabolic networks in a microbial pathogen. New methods are needed to understand complex cellular processes such as metabolism. This proposal will support the development of methods in metabolite profiling and flux analysis that provide a global view of metabolic networks in cells and complement other profiling approaches, such as proteomics and transcriptomics. The development of these approaches (collectively termed Systems Biology) is essential for maintaining Australia sc ....Characterization of metabolic networks in a microbial pathogen. New methods are needed to understand complex cellular processes such as metabolism. This proposal will support the development of methods in metabolite profiling and flux analysis that provide a global view of metabolic networks in cells and complement other profiling approaches, such as proteomics and transcriptomics. The development of these approaches (collectively termed Systems Biology) is essential for maintaining Australia science at the forefront of international efforts (National Research Priority 3; Breakthrough science). This project will also directly contribute to our understanding of metabolism of an important human pathogen and provide training to young Australian scientists.Read moreRead less
Multi-Colour Electrogenerated Chemiluminescence. This project plans to explore a new approach to chemical detection, in which molecules that emit different coloured light can be selectively switched on or switched off via the applied electrode potential. This would enable unprecedented numbers of simultaneous (multiplexed) detection events for time-critical analytical applications such as clinical diagnostics, environmental monitoring and biodefense assays. These assays could be performed on low ....Multi-Colour Electrogenerated Chemiluminescence. This project plans to explore a new approach to chemical detection, in which molecules that emit different coloured light can be selectively switched on or switched off via the applied electrode potential. This would enable unprecedented numbers of simultaneous (multiplexed) detection events for time-critical analytical applications such as clinical diagnostics, environmental monitoring and biodefense assays. These assays could be performed on low-cost microfluidic platforms operated by portable consumer devices such as mobile phones. Expected outcomes may provide new capabilities in rapid screening for disease biomarkers, environmental pollutants and bioterrorism agents, using simple, low-cost, portable instrumentation.Read moreRead less
Ultrasensitive chemical analysis of single cells by mass spectrometry. This project aims to significantly improve the analysis of single cells by mass spectrometry with ultrahigh sensitivity. Molecular differences between cells in large populations can be important in many processes, including cell differentiation and signalling. However, most measurements result in the chemical heterogeneity between cells being masked by the bulk population. Recent discoveries now make it feasible to measure th ....Ultrasensitive chemical analysis of single cells by mass spectrometry. This project aims to significantly improve the analysis of single cells by mass spectrometry with ultrahigh sensitivity. Molecular differences between cells in large populations can be important in many processes, including cell differentiation and signalling. However, most measurements result in the chemical heterogeneity between cells being masked by the bulk population. Recent discoveries now make it feasible to measure thousands of proteins and small molecules from single cells. This project aims to leverage these breakthroughs to allow heterogeneity to be characterised in single cells with unprecedented molecular detail. This is expected to be important for future biological discovery, as well as disease prediction and drug discovery.Read moreRead less
Differential Isotope Proteome Mapping of Transforming Growth Factor Beta Cell Signalling. Our research will capitalise on Australia's expertise and prior infrastructure investments in frontier, proteomic technologies to elucidate novel intracellular signalling pathways that contribute to the development of cancer. New approaches will be developed using isotopes to provide sensitive and accurate measurements of changes in protein expression levels. This technology will allow us to define complex ....Differential Isotope Proteome Mapping of Transforming Growth Factor Beta Cell Signalling. Our research will capitalise on Australia's expertise and prior infrastructure investments in frontier, proteomic technologies to elucidate novel intracellular signalling pathways that contribute to the development of cancer. New approaches will be developed using isotopes to provide sensitive and accurate measurements of changes in protein expression levels. This technology will allow us to define complex intracellular signalling networks. This is an important step towards identifying new drug targets that are responsible for tumour growth. Australian science will benefit from the training of new scientists in modern, post-genome technologies where there is currently a world shortage of experienced personnel.Read moreRead less
Homogenous Antibody-Metal Conjugates For Immuno-Mass Spectrometry Imaging. This project aims to use bespoke metal labels and high-resolution mass spectrometry imaging to address current shortcomings in approaches that visualise and measure proteins in cells and tissue. It expects to substantially increase the utility of immuno-mass spectrometry imaging technology to analyses that are refractory to current techniques and workflows. Expected outcomes include metal probes that facilitate the spatia ....Homogenous Antibody-Metal Conjugates For Immuno-Mass Spectrometry Imaging. This project aims to use bespoke metal labels and high-resolution mass spectrometry imaging to address current shortcomings in approaches that visualise and measure proteins in cells and tissue. It expects to substantially increase the utility of immuno-mass spectrometry imaging technology to analyses that are refractory to current techniques and workflows. Expected outcomes include metal probes that facilitate the spatial quantification of multiple biomolecules on a single histological section, providing significant benefits to bioscience laboratories that require complex workflows to visualise and obtain quantitative data on the expression of biomolecules.Read moreRead less
The Impact of Changing Climatic Conditions inferred from the Isotope Abundances of Trace Metals in Global Ice Sheets and Glaciers. In this project Greenland and Antarctic ice-cores more than 3 km long will be used to investigate climatic variation extending back more that 4 complete glacial cycles. Some of these ice-cores include sections of refrozen water formed from sub-glacial Antarctic lake water. This project will use naturally occurring lead and strontium isotopic tracers to fingerprint ....The Impact of Changing Climatic Conditions inferred from the Isotope Abundances of Trace Metals in Global Ice Sheets and Glaciers. In this project Greenland and Antarctic ice-cores more than 3 km long will be used to investigate climatic variation extending back more that 4 complete glacial cycles. Some of these ice-cores include sections of refrozen water formed from sub-glacial Antarctic lake water. This project will use naturally occurring lead and strontium isotopic tracers to fingerprint impurities in the ice, because they have the potential to simultaneously signal the timing and location of past episodes of climate change. This will lead to an improvement in our understanding of the processes that cause these changes.Read moreRead less