Molecular analysis of glutathione transferase interactions with drugs and physiological ligands. Proteins called glutathione transferases protect us from toxic molecules that we ingest, breathe in or are by-products of normal metabolism. The same proteins also bind to many types of drugs leading them to be excreted from the body. In this project molecular structures of glutathione transferases bound to anti-cancer drugs will be determined as the basis for devising inhibitors of the protein that ....Molecular analysis of glutathione transferase interactions with drugs and physiological ligands. Proteins called glutathione transferases protect us from toxic molecules that we ingest, breathe in or are by-products of normal metabolism. The same proteins also bind to many types of drugs leading them to be excreted from the body. In this project molecular structures of glutathione transferases bound to anti-cancer drugs will be determined as the basis for devising inhibitors of the protein that will make drugs much more effective.Read moreRead less
Structural studies of glutathione transferases: a model system for functional genomics and drug design. Glutathione S-transferases (GSTs) are a large family of multi-functional proteins that play a vital role in an organism's defence against toxic chemicals. However, they also attack a variety of drugs and hence are a prime target for the development of isoform-specific inhibitors. We will determine the 3D atomic structures of GSTs in complex with a range of substrates and inhibitors as a basis ....Structural studies of glutathione transferases: a model system for functional genomics and drug design. Glutathione S-transferases (GSTs) are a large family of multi-functional proteins that play a vital role in an organism's defence against toxic chemicals. However, they also attack a variety of drugs and hence are a prime target for the development of isoform-specific inhibitors. We will determine the 3D atomic structures of GSTs in complex with a range of substrates and inhibitors as a basis for the design of compounds to improve the efficacy of anti-cancer and other drugs. This is an ambitious, wide-ranging project involving collaborators around the world. We expect the results will not only greatly increase our knowledge of an important enzyme family, but will also have applications in protein folding, catalysis, protein engineering, evolution, drug design and functional genomics. Read moreRead less
Elucidating the chemical and biophysical basis for the bioactivity of cyclotides: ultra-stable proteins from plants. The national/community benefits that are expected to arise from this research are economic and social in nature. In particular, this project has the potential to increase the national capacity for the development of peptides (mini-proteins) as anti-cancer drugs. With blockbuster protein-based drugs having sales in excess of $10 billion per annum this proposal has the potential for ....Elucidating the chemical and biophysical basis for the bioactivity of cyclotides: ultra-stable proteins from plants. The national/community benefits that are expected to arise from this research are economic and social in nature. In particular, this project has the potential to increase the national capacity for the development of peptides (mini-proteins) as anti-cancer drugs. With blockbuster protein-based drugs having sales in excess of $10 billion per annum this proposal has the potential for very significant economic benefits for Australia. As well as these economic benefits a novel therapeutic agent for cancer would have enormous social benefits for Australia by decreasing the number of individuals affected and thereby reducing the subsequent emotional and physical distress associated with cancer. Read moreRead less
TiO2 nanoparticle design and photocatalysis applications. The aim is to design nanosized TiO2 photocatalsysts with superior photoactivity using various synthesis paths. Nanosized TiO2 particles will be prepared using sol-gel, aerosol and plasma processing, their physical and chemical properties will be closely studied and their photocatalytic ability will be assessed. Such tailor-made photocatalysts have significant commercial potential value, as they would be highly suitable for the photooxidat ....TiO2 nanoparticle design and photocatalysis applications. The aim is to design nanosized TiO2 photocatalsysts with superior photoactivity using various synthesis paths. Nanosized TiO2 particles will be prepared using sol-gel, aerosol and plasma processing, their physical and chemical properties will be closely studied and their photocatalytic ability will be assessed. Such tailor-made photocatalysts have significant commercial potential value, as they would be highly suitable for the photooxidation of organic compounds and the photoreduction of metal ions in wastewaters. Findings from this work will pave the way for a "green" technology such as photocatalysis to become more efficient and hence a competitive alternative to conventional water treatment methods.Read moreRead less
Global genetic regulation of carbon metabolism in filamentous fungi. Fungi are of great importance in medicine, agriculture and industry. They are used extensively for food, antibiotic and chemical production and, increasingly, for generating cheap substrates for bioethanol. However many are serious pathogens of plants and humans. Understanding how fungi control their metabolism is of fundamental importance for their more effective use or control. This project takes advantage of a fungus that is ....Global genetic regulation of carbon metabolism in filamentous fungi. Fungi are of great importance in medicine, agriculture and industry. They are used extensively for food, antibiotic and chemical production and, increasingly, for generating cheap substrates for bioethanol. However many are serious pathogens of plants and humans. Understanding how fungi control their metabolism is of fundamental importance for their more effective use or control. This project takes advantage of a fungus that is easily studied in the laboratory by advanced genetic techniques to identify the ways in which genes are turned on and off in response to changes in the nutrients available. By comparing DNA sequences the results are readily applied to fungi of economic importance.Read moreRead less
Nanostructured Degradable Polymer for Drug Delivery. The success of synthesising nanostructured degradable polymers will position Australia at the world forefront in the field of nanotechnology, bioengineering and healthcare sectors in both fundamental and applied research. This multi-disciplinary research has the potential to generate patentable technologies with economic benefits to Australia. The project also involves fundamental research into surface chemistry, nanostructure, polymer science ....Nanostructured Degradable Polymer for Drug Delivery. The success of synthesising nanostructured degradable polymers will position Australia at the world forefront in the field of nanotechnology, bioengineering and healthcare sectors in both fundamental and applied research. This multi-disciplinary research has the potential to generate patentable technologies with economic benefits to Australia. The project also involves fundamental research into surface chemistry, nanostructure, polymer sciences and will be a meaningful contribution to the advancement of scientific knowledge in Australia. All these will enhance the international competitive profile of Australia in the field of nanotechnology for drug delivery.Read moreRead less
Experimental and Theoretical Studies of Vanadium Oxide Nanostructures and Their Functional Properties. This project is primarily devoted to material science and nanotechnology, one of the cutting-edge areas in Australia's National Research Priority. Successful completion of this project will result in controlled synthesis, functional assembly and fundamental understanding of vanadium oxide nanostructures. The research findings will be useful for developing new and complex nanostructures for func ....Experimental and Theoretical Studies of Vanadium Oxide Nanostructures and Their Functional Properties. This project is primarily devoted to material science and nanotechnology, one of the cutting-edge areas in Australia's National Research Priority. Successful completion of this project will result in controlled synthesis, functional assembly and fundamental understanding of vanadium oxide nanostructures. The research findings will be useful for developing new and complex nanostructures for functional applications in lithium ionic batteries, catalysts and gas sensors. The conduct of this project will significantly expand the knowledge creativity of Australia in research in advanced materials.Read moreRead less
REGULATION OF RYANODINE RECEPTOR CALCIUM CHANNELS BY THE CALCIUM BINDING PROTEIN CALSEQUESTRIN. The project is to examine the functional interaction between two proteins in skeletal muscle that are essential for Ca2+ regulation and hence contraction, respiration and movement in all vertebrate species. One protein, the ryanodine receptor, releases calcium from stores inside the muscle cell. The other protein, calsequestrin, binds and sequesters calcium ions. We have recently discovered that th ....REGULATION OF RYANODINE RECEPTOR CALCIUM CHANNELS BY THE CALCIUM BINDING PROTEIN CALSEQUESTRIN. The project is to examine the functional interaction between two proteins in skeletal muscle that are essential for Ca2+ regulation and hence contraction, respiration and movement in all vertebrate species. One protein, the ryanodine receptor, releases calcium from stores inside the muscle cell. The other protein, calsequestrin, binds and sequesters calcium ions. We have recently discovered that the proteins also bind to each other and that calsequestrin regulates Ca2+ release from the stores through the ryanodine receptor ion channel. This regulation is likely to be important in conserving store calcium during stress or fatigue.Read moreRead less
A novel approach to fighting fungal infections: targeted disruption of hydrophobin monolayers. Fungal infestations of important crops such as cotton cause large economic losses to Australian agriculture while in the medical sector, fungal infections are responsible for high levels of mortality in immunocompromised patients. Our research will provide a new approach to fighting fungal infections by targeting the hydrophobin proteins, which form a robust coating on fungal aerial structures, such as ....A novel approach to fighting fungal infections: targeted disruption of hydrophobin monolayers. Fungal infestations of important crops such as cotton cause large economic losses to Australian agriculture while in the medical sector, fungal infections are responsible for high levels of mortality in immunocompromised patients. Our research will provide a new approach to fighting fungal infections by targeting the hydrophobin proteins, which form a robust coating on fungal aerial structures, such as spores. This layer is critical for fungal growth and reproduction and confers water resistance and tolerance to harsh conditions. Our work seeks to develop reagents that can specifically block regions on the protein that are responsible for forming this coating.
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Supramolecular Assemblies as Nanoscale Devices to Control Chemical and Physical Processes. The aims of this project are: i) to develop molecular reaction vessels to enhance the rates and control the outcomes of chemical processes; ii) to design and construct supramolecular species with a range of topologies; and iii) to explore the potential use of these supramolecular assemblies as thermal and photochemical switches and molecular tweezers, and as the basis for molecular machines and microelectr ....Supramolecular Assemblies as Nanoscale Devices to Control Chemical and Physical Processes. The aims of this project are: i) to develop molecular reaction vessels to enhance the rates and control the outcomes of chemical processes; ii) to design and construct supramolecular species with a range of topologies; and iii) to explore the potential use of these supramolecular assemblies as thermal and photochemical switches and molecular tweezers, and as the basis for molecular machines and microelectronic devices. The research is expected to provide new and efficient methods for bench-top and industrial scale synthesis of chemicals in water, as well as fundamental advances in nanotechnology to underpin new industries based on advanced materials.Read moreRead less