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
Toll Like Receptor signalling as a mediator of sex differences in pain, opioid and alcohol action. Brain immunology will be examined in this project to see if the signalling of a receptor called Toll Like Receptor 4 can explain sex differences in pain, and the action of pain killers and alcohol. These findings will have significant implications on the understanding of male and female brains, and will assist in the design of new drugs to treat brain and spinal cord diseases.
Huntingtin-associated protein 1 controls cell communication. The purpose of this study is to identify the mechanisms by which a novel regulator of cell communication which we have identified is able to control the release of chemical signals from a cell. This project will provide critical insight into a cellular pathway that underlies hormone secretion, neurotransmission and higher brain functions.
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
Surface Engineered Biomaterials to Control Inflammation. The overarching aim of this project is to provide a mechanistic understanding of how surface nanotopography affects inflammatory responses. Experimental evidence demonstrates that engineered surface nanotopography in combination with surface chemistry downregulates the expression of proinflammatory cytokines from primary macrophages. The significance of these findings is that it may be possible to engineer the nanotopography of a biomedica ....Surface Engineered Biomaterials to Control Inflammation. The overarching aim of this project is to provide a mechanistic understanding of how surface nanotopography affects inflammatory responses. Experimental evidence demonstrates that engineered surface nanotopography in combination with surface chemistry downregulates the expression of proinflammatory cytokines from primary macrophages. The significance of these findings is that it may be possible to engineer the nanotopography of a biomedical device surface in a manner which leads to a desired and predictable level of inflammation and subsequent foreign body reaction (FBR) medical implants and tissue engineering constructs.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