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
How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misf ....How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misfolded proteins during ageing, within the nervous system of a living animal. Expected outcomes of this project will generate new knowledge of brain physiology and ageing relevant to all animals. This should provide significant benefits, such as a greater understanding of long-term brain functions including memory.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
TREX-mediated nuclear mRNA export in neuronal differentiation and function. This project aims to study nucleus-to-cytoplasm information flow and the cellular toolbox required for this process. To ensure competitive growth and survival, plant and animal cells have sophisticated mechanisms of information transfer. One such process is efficient export of molecules from the cell nucleus (the coding space) to the cell cytoplasm (the protein synthesis space). This project will use a cell-based system ....TREX-mediated nuclear mRNA export in neuronal differentiation and function. This project aims to study nucleus-to-cytoplasm information flow and the cellular toolbox required for this process. To ensure competitive growth and survival, plant and animal cells have sophisticated mechanisms of information transfer. One such process is efficient export of molecules from the cell nucleus (the coding space) to the cell cytoplasm (the protein synthesis space). This project will use a cell-based system that can precisely control different aspects of the toolbox performance to understand this process. The knowledge and resources generated can be used to develop products or services with tangible economic and health benefits.Read moreRead less
Mechanisms of memory function involving site-specific tau phosphorylation. This project aims to understand the molecular principles that facilitate encoding, maintenance and retrieval of memories in the brain. To store memories in brain circuits, electrical and chemical signals are crucial. Brain cells can integrate signals into biochemical modifications of intracellular proteins. The nature of the protein modifications that represent memory within brain cells is unknown. This project uses innov ....Mechanisms of memory function involving site-specific tau phosphorylation. This project aims to understand the molecular principles that facilitate encoding, maintenance and retrieval of memories in the brain. To store memories in brain circuits, electrical and chemical signals are crucial. Brain cells can integrate signals into biochemical modifications of intracellular proteins. The nature of the protein modifications that represent memory within brain cells is unknown. This project uses innovative genome editing, mathematical modelling and proteomic approaches, to study how biochemical modifications of a key protein called tau help encode and retrieve memories. These molecular insights will make a significant advance in the current understanding of a brain function that is essential to all human activities.Read moreRead less
Molecular control of memory traces. This project aims to understand how particular molecules help encode memories in the brain for future retrieval. Individual memories are encoded in brain cells through an unknown physical process. This project uses innovative approaches to manipulate memory-containing cells and will provide a new detailed explanation of memory. Outcomes of this work will significantly advance the current understanding of how memories are physically generated and maintained, wh ....Molecular control of memory traces. This project aims to understand how particular molecules help encode memories in the brain for future retrieval. Individual memories are encoded in brain cells through an unknown physical process. This project uses innovative approaches to manipulate memory-containing cells and will provide a new detailed explanation of memory. Outcomes of this work will significantly advance the current understanding of how memories are physically generated and maintained, which is an essential component of human and animal life. This research provides significant benefits in understanding the biology behind memory and in maintaining memory capacity in ageing.
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Pair bonding: is it all in the brain? This project aims to understand the interaction between classic pair bonding neural circuits, parasites, and the immune system in sleepy lizards. Social bonds are a cornerstone of human societies, especially true of the pair bond and this project expects to generate knowledge to help understand why healthy adult pair bonds are the single best predictor of longevity in humans. The expected outcomes of this project are to reveal the mechanistic basis of pair b ....Pair bonding: is it all in the brain? This project aims to understand the interaction between classic pair bonding neural circuits, parasites, and the immune system in sleepy lizards. Social bonds are a cornerstone of human societies, especially true of the pair bond and this project expects to generate knowledge to help understand why healthy adult pair bonds are the single best predictor of longevity in humans. The expected outcomes of this project are to reveal the mechanistic basis of pair bonding by identifying the brain regions, cell types and neurochemicals that promote pair bonding behaviour — for the first time in a wild animal. This project should provide significant benefits by increasing our knowledge of how pair bonds promote wellness.Read moreRead less