Refinement of dynamic combinatorial chemistry as a drug discovery tool. Medicinal chemistry is constantly being challenged to develop efficient methodologies for the synthesis of compounds for drug discovery. Following completion of the Human Genome project, the cloning and expression of new proteins will proceed at an accelerated rate. In the absence of biochemical knowledge of the target protein there is a growing interest in techniques that expand the structural and biological diversity of co ....Refinement of dynamic combinatorial chemistry as a drug discovery tool. Medicinal chemistry is constantly being challenged to develop efficient methodologies for the synthesis of compounds for drug discovery. Following completion of the Human Genome project, the cloning and expression of new proteins will proceed at an accelerated rate. In the absence of biochemical knowledge of the target protein there is a growing interest in techniques that expand the structural and biological diversity of compound libraries. Dynamic combinatorial chemistry is an innovative technology with the capacity for supporting the shift from focussed to diverse compound libraries. This application seeks funding to refine dynamic combinatorial chemistry into an effective drug discovery tool.Read moreRead less
Coenzyme Q as a measure of environmental stress in aquatic ecosystems. Australia's marine and freshwater water resources including high profile regions such as the Great Barrier Reef and the Murray-Darling River system are under increasing threat. This project is significant as it aims to provide a rapid tool to quantify low-level impacts in aquatic systems and provide a novel and accurate early-warning-system of stress within aquatic environments. Through the innovative development of an assay ....Coenzyme Q as a measure of environmental stress in aquatic ecosystems. Australia's marine and freshwater water resources including high profile regions such as the Great Barrier Reef and the Murray-Darling River system are under increasing threat. This project is significant as it aims to provide a rapid tool to quantify low-level impacts in aquatic systems and provide a novel and accurate early-warning-system of stress within aquatic environments. Through the innovative development of an assay system from proven biomedical technologies it will be possible to deliver a significant community benefit by providing an early warning mechanism for the combined effects of urban and industrial impacts on our invaluable marine and freshwater resources.Read moreRead less
New laser and mass spectrometry-based tools for comprehensive structural elucidation of lipids and their biomolecular interactions. Lipid-related disorders such as obesity, diabetes and heart disease are reaching epidemic proportions. We propose the development of specialised instrumentation to identify and quantify lipids (fats) in tissue and culture samples thus providing Australian scientists with unique capabilities to investigate the mechanisms of disease.
Pluses and minuses of lipid mass spectrometry. This project aims to investigate the structural diversity of lipids. Lipids are among the most structurally diverse of all the biomolecules and thus deciphering their many functions requires bio-analytical technologies capable of uniquely identifying and quantifying individual molecules in a milieu of many thousands of analogues. Mass spectrometry is the pre-eminent technique for contemporary lipid analysis but is challenged by the preference of cer ....Pluses and minuses of lipid mass spectrometry. This project aims to investigate the structural diversity of lipids. Lipids are among the most structurally diverse of all the biomolecules and thus deciphering their many functions requires bio-analytical technologies capable of uniquely identifying and quantifying individual molecules in a milieu of many thousands of analogues. Mass spectrometry is the pre-eminent technique for contemporary lipid analysis but is challenged by the preference of certain lipids to ionise with a polarity that affords sensitive detection but does not permit detailed structure elucidation. This project will develop advanced instrumentation capable of on-demand polarity switching of ionised lipids such that the detection and interrogation of molecular structure can take place in the optimal charge state.Read moreRead less
Developing next generation technologies for unmasking the lipidome. Recent discoveries suggest that the number and structural variety of lipids in nature may be far greater than previously imagined. This complexity arises from the presence of structurally similar, but functionally distinct, lipid isomers that are not readily distinguished using current lipidomics technologies. This project aims to develop unique instrumentation that combines ion mobility and mass spectrometry to enable the rapid ....Developing next generation technologies for unmasking the lipidome. Recent discoveries suggest that the number and structural variety of lipids in nature may be far greater than previously imagined. This complexity arises from the presence of structurally similar, but functionally distinct, lipid isomers that are not readily distinguished using current lipidomics technologies. This project aims to develop unique instrumentation that combines ion mobility and mass spectrometry to enable the rapid separation, identification and quantification of isomeric lipids. These next generation technologies will be deployed in the hope of unmasking the molecular diversity within the lipidomes of two important mammalian cell types, thus providing fundamental new insights into the structure and function of lipids within living systems.Read moreRead less
New biosensing strategies based on bipolar electrochemiluminescence. Chemical analysis is a vital activity in our society, which is to a large extent confined to scientific laboratories and carried out with complex instrumentation. The breakthrough technology envisioned in this proposal will pave the way for simple, low-cost tests which can be used by non-scientists. The development of small, portable sensors for applications ranging from pollution monitoring to health testing, will enable ordi ....New biosensing strategies based on bipolar electrochemiluminescence. Chemical analysis is a vital activity in our society, which is to a large extent confined to scientific laboratories and carried out with complex instrumentation. The breakthrough technology envisioned in this proposal will pave the way for simple, low-cost tests which can be used by non-scientists. The development of small, portable sensors for applications ranging from pollution monitoring to health testing, will enable ordinary people to gain knowledge about the concentrations of molecular compounds in their environments and in themselves. This will stimulate economic and social benefits related to environmental testing and early disease diagnosis and generate new commercial opportunities for the Australian biotechnology industry.Read moreRead less
The photons take charge: Elucidating the structure and stability of distonic radical anions by mass spectrometry and photoelectron spectroscopy. Recent work has discovered that certain radical anions have electronic configurations that defy chemical convention and exhibit exceptional radical stability. Exploitation of this breakthrough first requires experimental elucidation of the intrinsic electronic structure of these compounds and how it relates to their remarkable properties. This project w ....The photons take charge: Elucidating the structure and stability of distonic radical anions by mass spectrometry and photoelectron spectroscopy. Recent work has discovered that certain radical anions have electronic configurations that defy chemical convention and exhibit exceptional radical stability. Exploitation of this breakthrough first requires experimental elucidation of the intrinsic electronic structure of these compounds and how it relates to their remarkable properties. This project will probe the fundamental structure and energetics of radical anions by modifying instrumentation to enable multi-step gas-phase ion synthesis to be efficiently coupled with anion photoelectron spectroscopy. These investigations are essential to revealing the scope of this phenomenon in free radical chemistry and biology and could inform future development of new catalysts for polymerisation.Read moreRead less
Tuneable “Nano-Shearing”: An Innovative Mechanism for the Accurate and Specific Capture of Cells and Molecules. Recent investigations have discovered a tuneable electro-hydrodynamic force which drives lateral fluid motion within a few nanometers of an electrode surface. Because the magnitude of this fluid shear force can be tuned externally (for example, via the application of an AC electric field), it provides a new capability to physically displace weakly (non-specifically) bound cellular and ....Tuneable “Nano-Shearing”: An Innovative Mechanism for the Accurate and Specific Capture of Cells and Molecules. Recent investigations have discovered a tuneable electro-hydrodynamic force which drives lateral fluid motion within a few nanometers of an electrode surface. Because the magnitude of this fluid shear force can be tuned externally (for example, via the application of an AC electric field), it provides a new capability to physically displace weakly (non-specifically) bound cellular and molecular analytes. By performing research to further understand and develop this tuneable effect, this project aims to build and test a new platform technology to enable highly efficient capture and specific detection of low concentration pathogenic molecules and circulating tumour cells (CTCs).Read moreRead less
Understanding and controlling bioavailability: passive dosing of persistent organic pollutants into recombinant cell bioassays. Bioassays with mammalian cell lines may replace animal testing in chemical risk assessment if issues with limited sensitivity can be overcome for very hydrophobic chemicals such as polychlorinated dibenzodioxins. The project will solve this problem by developing a polymer-release dosing technique that assures defined and constant exposure.
Synthesis and Characterisation of Encoded Hybrid Polymer/Gold Nanoparticles for Application in Bioassays. Bioassays are the cornerstone of in vitro diagnostic and biomedical research. This proposal will significantly contribute to these areas, by targeting an emerging technology that is crucial for their future development. The hybrid nanoparticles described in this project have the potential to replace conventional detection strategies that are currently used for bioassays. In doing so, they sh ....Synthesis and Characterisation of Encoded Hybrid Polymer/Gold Nanoparticles for Application in Bioassays. Bioassays are the cornerstone of in vitro diagnostic and biomedical research. This proposal will significantly contribute to these areas, by targeting an emerging technology that is crucial for their future development. The hybrid nanoparticles described in this project have the potential to replace conventional detection strategies that are currently used for bioassays. In doing so, they should provide significant advantages over conventional detection strategies. These advantages include increased sample throughput and conservation of biological samples, which makes possible the acceleration of patient diagnosis and drug discovery. Read moreRead less