Immobilised Lipid Chromatography for Membrane Protein Isolation and Analysis. Current techniques for membrane protein are inadequate for the emerging proteomic challenge, in which approximately 40% of proteins are predicted to be membrane associated. The aim of this proposal is to develop a new approach to purify membrane proteins using our recently-developed immobilised membrane chromatography materials. The present proposal will provide a new high-resolution separation technique that allows is ....Immobilised Lipid Chromatography for Membrane Protein Isolation and Analysis. Current techniques for membrane protein are inadequate for the emerging proteomic challenge, in which approximately 40% of proteins are predicted to be membrane associated. The aim of this proposal is to develop a new approach to purify membrane proteins using our recently-developed immobilised membrane chromatography materials. The present proposal will provide a new high-resolution separation technique that allows isolation and on-line mass analysis of complex mixtures of membrane proteins for subsequent proteomic analysis, high-throughput screening or structural studies and could form the basis for further development of new commercial tools for membrane protein analysis.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
Elucidating the Mode of Action of Nicotinic Receptor Ligands. Changes in brain function can cause human diseases such as epilepsy, schizophrenia and Alzheimer's disease. To develop new medicines to treat these conditions we need to study how drugs act in the brain. This project will use new methods of chemistry to make drugs, which will then be tested for biological activity at important brain receptors. This will tell us which compounds are most effective as potential drugs and also exactly whe ....Elucidating the Mode of Action of Nicotinic Receptor Ligands. Changes in brain function can cause human diseases such as epilepsy, schizophrenia and Alzheimer's disease. To develop new medicines to treat these conditions we need to study how drugs act in the brain. This project will use new methods of chemistry to make drugs, which will then be tested for biological activity at important brain receptors. This will tell us which compounds are most effective as potential drugs and also exactly where they act in the brain. Read moreRead less
Elucidating the Mode of Action of Nicotinic Receptor Ligands. Changes in brain function can cause human diseases such as epilepsy, schizophrenia and Alzheimer's disease. To develop new medicines to treat these conditions we need to study how drugs act in the brain. This project will use new methods of chemistry to make drugs, which will then be tested for biological activity at important brain receptors. This will tell us which compounds are most effective as potential drugs and also exactly whe ....Elucidating the Mode of Action of Nicotinic Receptor Ligands. Changes in brain function can cause human diseases such as epilepsy, schizophrenia and Alzheimer's disease. To develop new medicines to treat these conditions we need to study how drugs act in the brain. This project will use new methods of chemistry to make drugs, which will then be tested for biological activity at important brain receptors. This will tell us which compounds are most effective as potential drugs and also exactly where they act in the brain. Read moreRead less
Development of Pyrrolopyrimidines as Inhibitors of ATP-Binding Proteins. This project seeks to generate analogues of natural products that have been found to be active against cancer cells and tropical parasites. The new materials produced by this project will aid in the study of biochemical processes involved in diseases such as cancer and lymphatic filariasis, thus leading the way to development of these compounds as potential treatments for such diseases.
Total chemical synthesis of a redesigned enzyme, HIV-1 PR, containing an artificial tunable catalytic apparatus. The research project proposed represents a novel approach using total chemical synthesis to study the enzyme action of the HIV-1 PR, an aspartyl protease essential for the replication of AIDS virus. The redesign of the catalytic apparatus will allow us to investigate molecular aspects of its action. The synthetic polypeptide chain will be folded and characterised for the correct folde ....Total chemical synthesis of a redesigned enzyme, HIV-1 PR, containing an artificial tunable catalytic apparatus. The research project proposed represents a novel approach using total chemical synthesis to study the enzyme action of the HIV-1 PR, an aspartyl protease essential for the replication of AIDS virus. The redesign of the catalytic apparatus will allow us to investigate molecular aspects of its action. The synthetic polypeptide chain will be folded and characterised for the correct folded structure by NMR, and assayed for enzymatic activity. It can be expected that significant new insights into the molecular basis of the properties of the HIV-1 PR will be obtained. This will be an important contribution to biomedical research.Read moreRead less
Synthesis and Functionalisation of Advanced Polymer Films and Particles. Scientific and technological advances at the frontiers of nano- and biotechnology are poised to revolutionise the scope of treatment and healthcare options. This project will involve the synthesis of engineered polymer building blocks with the capability for multifunctional and intelligent response. These smart polymers will then be assembled into responsive nanostructured materials for drug delivery and biosensing applica ....Synthesis and Functionalisation of Advanced Polymer Films and Particles. Scientific and technological advances at the frontiers of nano- and biotechnology are poised to revolutionise the scope of treatment and healthcare options. This project will involve the synthesis of engineered polymer building blocks with the capability for multifunctional and intelligent response. These smart polymers will then be assembled into responsive nanostructured materials for drug delivery and biosensing applications. These materials are expected to have health benefits for Australian citizens and will contribute to a world-leading nanobiotechnology industry. The project will also provide development opportunities for young scientists and will also foster multidisciplinary collaborations within both Australia and abroad.Read moreRead less
Design and Synthesis of Photoactive Peptides Based on Photosynthetic Reaction Centres. The aim of this proposal is to generate new and useful electron transfer components for biotechnological applications. We plan to design and synthesize artificial photoactive peptides inspired from natural photosynthetic reaction centres which capture the energy of light and convert it into usable forms of chemical energy. Our research will provide the ground work for the development of light-driven oxidation- ....Design and Synthesis of Photoactive Peptides Based on Photosynthetic Reaction Centres. The aim of this proposal is to generate new and useful electron transfer components for biotechnological applications. We plan to design and synthesize artificial photoactive peptides inspired from natural photosynthetic reaction centres which capture the energy of light and convert it into usable forms of chemical energy. Our research will provide the ground work for the development of light-driven oxidation-reduction catalysts that can be used in the production of clean fuels and chemical products.Read moreRead less
The design and synthesis of angiotensin converting enzyme-2 (ACE2) inhibitors. A vast number of current drugs on the market are inhibitors of enzymes whose action needs to be controlled in order to treat many conditions. This proposal will apply our new approaches to the design of enzyme inhibitors with superior therapeutic action. The benefits of this research reside in new treatments for a range of cardiovascular diseases (the 3rd largest cause of mortality in Australia) and provide a platform ....The design and synthesis of angiotensin converting enzyme-2 (ACE2) inhibitors. A vast number of current drugs on the market are inhibitors of enzymes whose action needs to be controlled in order to treat many conditions. This proposal will apply our new approaches to the design of enzyme inhibitors with superior therapeutic action. The benefits of this research reside in new treatments for a range of cardiovascular diseases (the 3rd largest cause of mortality in Australia) and provide a platform for new biotech companies to be formed in Australia.Read moreRead less
Generation and Exploitation of Fermentation Products in the Chemical Synthesis of Biologically Active Compounds with Therapeutic Potential. Dramatic developments in biotechnology have provided access to genetically engineered micro-organisms capable of effecting unusual transformations so as to form novel compounds of great value in chemical synthesis. This project will combine the powers of biotechnology with those of chemical synthesis to produce compounds that have therapeutic potential in th ....Generation and Exploitation of Fermentation Products in the Chemical Synthesis of Biologically Active Compounds with Therapeutic Potential. Dramatic developments in biotechnology have provided access to genetically engineered micro-organisms capable of effecting unusual transformations so as to form novel compounds of great value in chemical synthesis. This project will combine the powers of biotechnology with those of chemical synthesis to produce compounds that have therapeutic potential in the treatment of Alzheimer's disease, cancer and viral infections.Read moreRead less