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
Periodic nano-ratchets: a new paradigm for biomolecule separation. This project proposes the theoretical and experimental study of a new separation principle. The platform technologies developed from this research will see wide ranging applications. They will reveal new insights into fundamental phenomena of membranes and separation processes underpinning development of new generation of separation technologies. New membranes and microchip separation devices which can be applied to genomic, prot ....Periodic nano-ratchets: a new paradigm for biomolecule separation. This project proposes the theoretical and experimental study of a new separation principle. The platform technologies developed from this research will see wide ranging applications. They will reveal new insights into fundamental phenomena of membranes and separation processes underpinning development of new generation of separation technologies. New membranes and microchip separation devices which can be applied to genomic, proteomic, forensic and a range medical, biotechnological and analytical applications will be readily achievable. This is an international and interdisciplinary research project and its outcomes will enhance Australia's ability in frontier technologies, advanced materials.Read moreRead less
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
Novel approaches to the forensic identification of human remains: integration of studies of bone form and chemistry. In a global era of terrorism, crime and even natural disasters, new approaches to identify victims, and prosecute offenders, are greatly required and long overdue. The combination of new computer and chemical methods will help identify unknowns, reconstruct missing parts and separate commingled remains. Its affect on understanding bones may be like that of DNA on soft tissues. The ....Novel approaches to the forensic identification of human remains: integration of studies of bone form and chemistry. In a global era of terrorism, crime and even natural disasters, new approaches to identify victims, and prosecute offenders, are greatly required and long overdue. The combination of new computer and chemical methods will help identify unknowns, reconstruct missing parts and separate commingled remains. Its affect on understanding bones may be like that of DNA on soft tissues. The results will update our ability as forensic scientists to strengthen Australian security systems by improving our ability to manage accidents, disasters, terrorism and crime. This project will start international collaborations and train a new generation of Australian forensic experts.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
Fluorine-labelled proteins for NMR spectroscopy. The technique developed in this project has direct impact on pharmaceutical research: NMR spectroscopy is used routinely to identify chemical compounds that bind to protein targets. This project includes the development of novel assignment techniques of 19F-labelled proteins, so that 19F-NMR can be used to detect specific binding interactions. One of the methods proposed here is designed to reveal structural information about the binding mode in s ....Fluorine-labelled proteins for NMR spectroscopy. The technique developed in this project has direct impact on pharmaceutical research: NMR spectroscopy is used routinely to identify chemical compounds that bind to protein targets. This project includes the development of novel assignment techniques of 19F-labelled proteins, so that 19F-NMR can be used to detect specific binding interactions. One of the methods proposed here is designed to reveal structural information about the binding mode in solution with atomic detail. This knowledge can significantly accelerate drug development. It is otherwise only available from crystal structures that can not always be determined.Read moreRead less
Molecular Framework Materials: Nanoporosity and Anomalous Thermal Expansion. The design and construction of advanced nanomaterials represents both a key area of fundamental research and a critical step in the push towards smarter and more efficient high-level technologies. Here we explore the strategic assembly of molecular materials that have entirely new and highly useful properties, namely, nanoporosity and anomalous thermal expansion. This innovative work will lead to important fundamental ....Molecular Framework Materials: Nanoporosity and Anomalous Thermal Expansion. The design and construction of advanced nanomaterials represents both a key area of fundamental research and a critical step in the push towards smarter and more efficient high-level technologies. Here we explore the strategic assembly of molecular materials that have entirely new and highly useful properties, namely, nanoporosity and anomalous thermal expansion. This innovative work will lead to important fundamental advances in nanoscience and will forge deep understandings of how materials properties relate to nanoscale structure. These advances will spur a wide range of important new technologies, with application of the materials in molecular separations and sensing, clean energy storage, electronics and photonics.Read moreRead less
Metal Directed Assembly of New Discrete and Framework Supramolecular Systems. An important aspect of this project is the development of strategies for assembling molecules and metals into larger units - leading to novel compounds and materials for which unusual and potentially useful properties can be anticipated. These may include materials that act as catalysts for chemical reactions or absorb and store gases (such as hydrogen for use as a fuel). More generally, the area is one that will under ....Metal Directed Assembly of New Discrete and Framework Supramolecular Systems. An important aspect of this project is the development of strategies for assembling molecules and metals into larger units - leading to novel compounds and materials for which unusual and potentially useful properties can be anticipated. These may include materials that act as catalysts for chemical reactions or absorb and store gases (such as hydrogen for use as a fuel). More generally, the area is one that will underpin the 'bottom-up' approach (building tiny components from individual molecules and ions) in the rapidly expanding field of nanotechnology. Clearly, if Australia is to remain internationally competitive in such new technologies then an understanding of processes of the type outlined in this proposal will be essential.Read moreRead less
Metal Directed Assembly of New Supramolecular Systems. An important aspect of this project is the development of strategies for assembling molecules and metals into larger units - leading to novel compounds and materials for which unusual and potentially useful properties can be anticipated. These may include materials that act as catalysts for chemical reactions or absorb and store gases (such as hydrogen for use as a fuel). More generally, the area is one that will underpin the 'bottom-up' ap ....Metal Directed Assembly of New Supramolecular Systems. An important aspect of this project is the development of strategies for assembling molecules and metals into larger units - leading to novel compounds and materials for which unusual and potentially useful properties can be anticipated. These may include materials that act as catalysts for chemical reactions or absorb and store gases (such as hydrogen for use as a fuel). More generally, the area is one that will underpin the 'bottom-up' approach (building tiny components from individual molecules and ions) in the rapidly expanding field of nanotechnology. Clearly, if Australia is to remain internationally competitive in such new technologies then an understanding of processes of the type outlined in this proposal will be essential.Read moreRead less