New strategies for the stereoselective synthesis of Stemona alkaloids and the discovery of new bioactive molecules. The project aims to develop innovative methods to prepare bioactive natural products and their analogues with potential applications as new and safer therapeutic drugs and agricultural chemicals. These products would be of benefit to Australians in the future.
Molecular mechanisms of catalysis and the basis of substrate specificity in polysaccharide hydrolases. Reaction intermediates along hydrolytic pathways and molecular determinants of substrate specificity of barley B-glucan exo- and endohydrolases will be defined using crystallographic and kinetic analyses. These enzymes are of central importance in cell wall metabolism during development of higher plants, and in plant-pathogen interactions. Realization of the project objectives will not only pro ....Molecular mechanisms of catalysis and the basis of substrate specificity in polysaccharide hydrolases. Reaction intermediates along hydrolytic pathways and molecular determinants of substrate specificity of barley B-glucan exo- and endohydrolases will be defined using crystallographic and kinetic analyses. These enzymes are of central importance in cell wall metabolism during development of higher plants, and in plant-pathogen interactions. Realization of the project objectives will not only provide fundamental information on catalytic mechanisms, but will also provide opportunities to manipulate enzyme specificity. Further, site-directed mutagenesis of the enzymes will be used to generate glycosynthases, which will be evaluated for their ability to synthesise novel oligosaccharide and polysaccharide products, some of which might show immunomodulating activity.Read moreRead less
Characterisation of the beneficial vs toxic forms of selenium in the diet. This project aims to examine how dietary selenium is converted into essential proteins and beneficial compounds that mitigate against a broad range of human diseases; or alternatively, into toxic molecules. Cutting-edge methodologies should resolve significant unknowns in selenium metabolism, to provide definitive dietary guidelines and to explore how selenium can treat and protect against disease. Expected outcomes from ....Characterisation of the beneficial vs toxic forms of selenium in the diet. This project aims to examine how dietary selenium is converted into essential proteins and beneficial compounds that mitigate against a broad range of human diseases; or alternatively, into toxic molecules. Cutting-edge methodologies should resolve significant unknowns in selenium metabolism, to provide definitive dietary guidelines and to explore how selenium can treat and protect against disease. Expected outcomes from this national and international collaboration include expert training for young biochemical researchers and refinements to novel analytical techniques. Results should benefit the food and agricultural sectors to provide tailored products locally and for export, as well as enhanced health opportunities for all Australians.Read moreRead less
Taking nature's lead in the development of new and improved enzyme inhibitors. This project will address some key fundamental issues associated with advancing a chemical entity from proof of principle through to a new pharmaceutical. The compounds in the study target cancer, cataract and other diseases that are confronting Australia's ageing population.
Interactions between cells and extracellular matrix in the epithelial-mesenchymal transition of the ovarian follicular stratified epithelium. The lining of many mammalian organs and cavities contain cells that can transform into different cells to bring about organ development or repair but if it goes horribly wrong the cells become metastatic cancers. This project examines the key features of this process especially the roles of matrix that develops around the cells in this process.
Male to female sperm signalling – a new role for sperm in reproduction? Male seminal fluid is commonly thought simply to provide sperm for conception. This project aims to investigate a lesser known action of sperm: modifying the female immune response to increase the chances of reproductive success. The project aims to define the molecular pathway through which sperm interact with female cells, particularly how B-defensins on sperm bind to Toll-like receptors to stimulate female immune toleranc ....Male to female sperm signalling – a new role for sperm in reproduction? Male seminal fluid is commonly thought simply to provide sperm for conception. This project aims to investigate a lesser known action of sperm: modifying the female immune response to increase the chances of reproductive success. The project aims to define the molecular pathway through which sperm interact with female cells, particularly how B-defensins on sperm bind to Toll-like receptors to stimulate female immune tolerance. The project plans to use embryo transfer and genetic mouse models to determine the physiological benefit of sperm signalling. Evidence that seminal fluid signalling operates in mammals to ensure optimal female reproductive investment would advance knowledge of the male contribution to the reproductive process.Read moreRead less
Novel cell wall genes ripe for the picking. This project aims to investigate the role of recently discovered plant cellulose synthase-like CslM genes and to define the polysaccharide product associated with them. Successful identification of the polysaccharide is highly likely to increase our fundamental understanding of how cell walls are made, how cells stick together or fall apart as well as facilitating the training of the next generation of cell wall biologists in challenging molecular and ....Novel cell wall genes ripe for the picking. This project aims to investigate the role of recently discovered plant cellulose synthase-like CslM genes and to define the polysaccharide product associated with them. Successful identification of the polysaccharide is highly likely to increase our fundamental understanding of how cell walls are made, how cells stick together or fall apart as well as facilitating the training of the next generation of cell wall biologists in challenging molecular and biochemical techniques. This new knowledge could increase our understanding of fruit ripening, and how it might be manipulated. This could have significant downstream commercial benefits if applied to breeding programs of economically important fruit such as grapes, tomatoes and strawberries.Read moreRead less
Combating fungal biofilm growth on surfaces. This project aims to establish a scientific basis for the design and development of thin coatings, for use on biomedical devices, that can resist the attachment of fungal cells and the ensuing formation of infectious fungal biofilms on their surfaces. Advancing mechanistic understanding of how physico-chemical properties of materials surfaces influence fungal attachment will enable rational development and optimisation of coating chemistries and struc ....Combating fungal biofilm growth on surfaces. This project aims to establish a scientific basis for the design and development of thin coatings, for use on biomedical devices, that can resist the attachment of fungal cells and the ensuing formation of infectious fungal biofilms on their surfaces. Advancing mechanistic understanding of how physico-chemical properties of materials surfaces influence fungal attachment will enable rational development and optimisation of coating chemistries and structures. Tethered antifungal compounds will be added to polymer surfaces by controlled polymerisation methods to provide active deterrence; factors such as conformational flexibility will be studied to optimise coatings, which may will prevent life-threatening infections and reduce healthcare costs.Read moreRead less