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
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
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
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
Signaling in the crypt: a novel metabolic pathway in intestinal stem cells. The gut is the most rapidly renewing tissue in the body, driven by a highly active stem cell niche. Bile acids are emerging as critical regulators of this stem cell niche and disruption of bile acid homeostasis has profoundly adverse effects on intestinal renewal and hence gut health. We are addressing a critical gap in our understanding of how bile acids are controlled within stem cell niche. The aim of the project is ....Signaling in the crypt: a novel metabolic pathway in intestinal stem cells. The gut is the most rapidly renewing tissue in the body, driven by a highly active stem cell niche. Bile acids are emerging as critical regulators of this stem cell niche and disruption of bile acid homeostasis has profoundly adverse effects on intestinal renewal and hence gut health. We are addressing a critical gap in our understanding of how bile acids are controlled within stem cell niche. The aim of the project is to define the critical role of a novel enzyme called UGT8 in controlling intestinal stem cell response to bile acids; this is achieved by modulating UGT8 activity in intestinal stem cell models and determining the effects on stem cell function and the key signalling pathways that control intestinal homeostasis and renewal.Read moreRead less
Use of mitochondrial electron transport chain mutants to evaluate how non-phosphorylating respiration influences plant metabolite profiles and stress tolerance. This project uses transgenic plant technology to elucidate how mitochondrial function impacts on the profile of metabolites in plant cell and tissues and whether altering these profiles influences a plant's ability tog row in harsh conditions. It will contribute to our fundamental knowledge of plant metabolism using a metabolomic anaylsi ....Use of mitochondrial electron transport chain mutants to evaluate how non-phosphorylating respiration influences plant metabolite profiles and stress tolerance. This project uses transgenic plant technology to elucidate how mitochondrial function impacts on the profile of metabolites in plant cell and tissues and whether altering these profiles influences a plant's ability tog row in harsh conditions. It will contribute to our fundamental knowledge of plant metabolism using a metabolomic anaylsis of plant stress response. This will be achieved using new high-throughput technologies, allowing reliable qualitative and quantitative analysis of large numbers of samples. This approach will compliment existing genomic and proteomic analyses of plants exposed to abiotic stress.Read moreRead less
EFR3: Novel gatekeeper of cell proliferation. This interdisciplinary, cross-institutional project uses leading-edge mass spectrometry and the yeast genetic model to enhance knowledge of fundamental signalling mechanisms common to cell proliferation of eukaryotic cells. Building on extensive preliminary data that identifies novel energy-stress control points, this research will generate insights into critical and conserved features of nutrient stress control of cell proliferation that ensures cel ....EFR3: Novel gatekeeper of cell proliferation. This interdisciplinary, cross-institutional project uses leading-edge mass spectrometry and the yeast genetic model to enhance knowledge of fundamental signalling mechanisms common to cell proliferation of eukaryotic cells. Building on extensive preliminary data that identifies novel energy-stress control points, this research will generate insights into critical and conserved features of nutrient stress control of cell proliferation that ensures cell survival. This project advances basic and applied biology. Its outcomes will be relevant to several research areas and industries, specifically to the propagation of cell cultures that nowadays contributes to the production of a myriad of biotechnical and pharmaceutical commodities.
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Target Of Rapamycin control of nutrient uptake. This project aims to study nutrient uptake in eukaryotes. It is expected to generate new knowledge of critical and conserved features of environmental and Target Of Rapamycin (TOR)-mediated control of nutrient uptake, specifically endocytosis, building on novel preliminary data that identifies novel TOR control points. The expected outcomes include new insights into mechanisms controlling nutrient uptake and fostering institutional collaboration. T ....Target Of Rapamycin control of nutrient uptake. This project aims to study nutrient uptake in eukaryotes. It is expected to generate new knowledge of critical and conserved features of environmental and Target Of Rapamycin (TOR)-mediated control of nutrient uptake, specifically endocytosis, building on novel preliminary data that identifies novel TOR control points. The expected outcomes include new insights into mechanisms controlling nutrient uptake and fostering institutional collaboration. This knowledge is highly relevant to any industry or research project utilising living organisms, as nutrient availability supports survival, cell growth and proliferation.Read moreRead less
How do cells survive nutrient stress? Insight into mechanisms. This project studies cell survival under nutrient stress in eukaryotes. Building on extensive preliminary data that identifies novel TOR (Target of Rapamycin) Complex 2 (TORC2) control points it expects to generate new knowledge of critical and conserved features of stress control of macroautophagy that ensures cell survival. It uses interdisciplinary and innovative approaches to validate and characterize nutrient-stress dependent si ....How do cells survive nutrient stress? Insight into mechanisms. This project studies cell survival under nutrient stress in eukaryotes. Building on extensive preliminary data that identifies novel TOR (Target of Rapamycin) Complex 2 (TORC2) control points it expects to generate new knowledge of critical and conserved features of stress control of macroautophagy that ensures cell survival. It uses interdisciplinary and innovative approaches to validate and characterize nutrient-stress dependent signaling. Expected outcomes include novel insights into environmental control of cell proliferation and forging cross institutional collaborations. This knowledge benefits basic and applied biology and is relevant to industries/projects utilizing living cells as nutrient supports cell survival and proliferation.Read moreRead less