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Gas phase studies of reactive organic radicals: a novel approach using mass spectrometry. Radical reactions play a crucial role in a range of important chemistries, ranging from the formation of photochemical smog to the accumulation of pathogens in the ageing body. Despite their importance, the reactions of many radicals are poorly understood because of current experimental limitations. In this project we propose to develop two new and broadly applicable techniques for probing radical chemistry ....Gas phase studies of reactive organic radicals: a novel approach using mass spectrometry. Radical reactions play a crucial role in a range of important chemistries, ranging from the formation of photochemical smog to the accumulation of pathogens in the ageing body. Despite their importance, the reactions of many radicals are poorly understood because of current experimental limitations. In this project we propose to develop two new and broadly applicable techniques for probing radical chemistry in the gas phase via novel applications of mass spectrometry. Combined with quantum chemical calculations and state-of-the-art thermodynamic measurements these methods will provide a comprehensive understanding of the reactivity of key organic radicals.Read moreRead less
Understanding and Inhibiting the P450 CYP24 enzyme, a target for cancer chemotherapeutics. This project falls within the National Research Priority of Promoting and Maintaining Good Health in the category of ageing well and productively. CYP24 inhibition provides a particular target for breast and prostate cancer which are the second leading cause of death in women and men, respectively. The proposed research will result in the production of CYP24 inhibitors that will be assessed in vivo at th ....Understanding and Inhibiting the P450 CYP24 enzyme, a target for cancer chemotherapeutics. This project falls within the National Research Priority of Promoting and Maintaining Good Health in the category of ageing well and productively. CYP24 inhibition provides a particular target for breast and prostate cancer which are the second leading cause of death in women and men, respectively. The proposed research will result in the production of CYP24 inhibitors that will be assessed in vivo at the Hanson Institute in Adelaide as potential anti-cancer drugs. Finally, there is a significant benefit in technology transfer to Australia from our collaborators in the USA in the field of computer aided inhibitor design.Read moreRead less
Material structure and properties of mineralised tissue: An integrated micro and nano level investigation. Bone material properties have a direct influence on disorders of the skeleton, such as osteoporotic bone fragility fractures and osteoarthritis. It has been estimated that the direct and indirect cost of all fragility fractures and arthritis is over $20 billion per annum. The impact of this will be far-reaching with the social benefits ranging from earlier and more accurate diagnoses, to t ....Material structure and properties of mineralised tissue: An integrated micro and nano level investigation. Bone material properties have a direct influence on disorders of the skeleton, such as osteoporotic bone fragility fractures and osteoarthritis. It has been estimated that the direct and indirect cost of all fragility fractures and arthritis is over $20 billion per annum. The impact of this will be far-reaching with the social benefits ranging from earlier and more accurate diagnoses, to the development of preventative strategies to delay the onset of musculoskeletal disorders. These developments will translate into exciting commercial opportunities and overall economic growth and sustainability.Read moreRead less
Identifying mitogenic signalling proteins with phosphatidyl inositol lipids. Health care of an ageing population is a national priority of the community. In order to understand the factors that control cell growth and death in cancer cells signalling proteins can be identified and studied and compared with model systems from quiescent cells. Using phospholipids attached to 'fishing lines' we can search for, identify and study the function of all the downstream signalling proteins in activated c ....Identifying mitogenic signalling proteins with phosphatidyl inositol lipids. Health care of an ageing population is a national priority of the community. In order to understand the factors that control cell growth and death in cancer cells signalling proteins can be identified and studied and compared with model systems from quiescent cells. Using phospholipids attached to 'fishing lines' we can search for, identify and study the function of all the downstream signalling proteins in activated cancer cells. This will provide the basic information for drug discovery processes to target specific molecules that inhibit and control the function of the signalling proteins implicated in the growth of cancer cells.Read moreRead less
Hydrogen Bonding, Hydrogen Transfer, Hydrogenation and Hydrogenolysis: A Computational Quantum Chemistry Investigation. This proposal aims to carry out state-of-the-art chemistry research using computer modelling rather than traditional laboratory methods. The computer calculations are directed towards designing catalysts that will provide more efficient ways to convert environmentally harmful carbon dioxide to a valuable chemical fuel methanol, and to convert toxic polychlorinated hydrocarbon ....Hydrogen Bonding, Hydrogen Transfer, Hydrogenation and Hydrogenolysis: A Computational Quantum Chemistry Investigation. This proposal aims to carry out state-of-the-art chemistry research using computer modelling rather than traditional laboratory methods. The computer calculations are directed towards designing catalysts that will provide more efficient ways to convert environmentally harmful carbon dioxide to a valuable chemical fuel methanol, and to convert toxic polychlorinated hydrocarbon wastes to benign products. The increased understanding of free radicals that will stem from this research may ultimately help in dealing with problems associated with heart disease, some forms of cancer and vitamin B12 deficiency. New generations of chemists will be trained at the highest level in this burgeoning field of computational chemistry.Read moreRead less
Membrane interactions and neurotoxicity of Amyloid Abeta peptides from Alzheimer's disease. A consequence of the increase in human life span is that age-related neurodegenerative diseases such as Alzheimer's disease (AD) are more prevalent. Currently there are limited therapeutic treatments and no cure for AD. The key protein causing AD is Abeta and characterization of the toxic species of this peptide is critical towards identifying potential therapeutic targets. This proposal aims to study mut ....Membrane interactions and neurotoxicity of Amyloid Abeta peptides from Alzheimer's disease. A consequence of the increase in human life span is that age-related neurodegenerative diseases such as Alzheimer's disease (AD) are more prevalent. Currently there are limited therapeutic treatments and no cure for AD. The key protein causing AD is Abeta and characterization of the toxic species of this peptide is critical towards identifying potential therapeutic targets. This proposal aims to study mutant peptides made synthetically and to identify a membrane-binding site. By establishing which lipid is critically involved in membrane binding of Abeta and mediating subsequent cell death, drugs may be developed to prevent the binding of Abeta to membranes resulting in neuronal survival and prevention of memory loss in AD patients.Read moreRead less
Synthesis of phosphatidylinositol and inositol polyphosphate derivatives to probe key signalling proteins associated with cell growth and cancer. Health care of an ageing population is a national priority of the community. In order to understand the factors that control cell growth and death in cancer cells signalling proteins can be identified and studied and compared with model systems from quiescent cells. Using phospholipids and inositol polyphosphates attached to 'fishing lines' we can sea ....Synthesis of phosphatidylinositol and inositol polyphosphate derivatives to probe key signalling proteins associated with cell growth and cancer. Health care of an ageing population is a national priority of the community. In order to understand the factors that control cell growth and death in cancer cells signalling proteins can be identified and studied and compared with model systems from quiescent cells. Using phospholipids and inositol polyphosphates attached to 'fishing lines' we can search for, identify and study the function of many of the downstream signalling proteins in activated cancer cells. This will provide the basic information for discovery processes to target specific molecules that inhibit and control the function of the signalling proteins implicated in the growth of cancer cells.Read moreRead less