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How SEP-like genes determine cereal inflorescence architecture. This project aims to understand the morphological diversity of inflorescence architecture between cereal crop species. To do so, this project will identify functions and analyse the regulatory networks of conserved SEPALLATA genes (SEPs). This will enable them to determine cereal inflorescence morphogenesis of rice (branching) and barley (non-branching), representing the most important cereals. Identifying and understanding rice and ....How SEP-like genes determine cereal inflorescence architecture. This project aims to understand the morphological diversity of inflorescence architecture between cereal crop species. To do so, this project will identify functions and analyse the regulatory networks of conserved SEPALLATA genes (SEPs). This will enable them to determine cereal inflorescence morphogenesis of rice (branching) and barley (non-branching), representing the most important cereals. Identifying and understanding rice and barley SEPs, their direct targets and interactors, and how they regulate inflorescence branches and spikelets in both species is expected to provide evolutionary and developmental insights and targets to improve for crop yield. A molecular understanding of the regulatory network that underpins inflorescence shape and grain number will advance fundamental biology, and could form the basis for significant yield improvements by manipulating key points in the developmental pathway.Read moreRead less
Phage display derived antibody fragments for membrane protein research. Membrane proteins are key components of all living organisms and represent more than 50 per cent of all drug targets. This project will redefine the way membrane proteins are studied and will be highly beneficial to basic research, human disease and the biotechnology industry.
Delineating the role of the GxxxG motif in transmembrane protein metabolism. This study will define how a well defined motif involved in transmembrane interactions affects the metabolism of proteins. Since this motif is present in proteins involved in Alzheimer's disease it has potential benefits for community health and combating ageing.
What limits CO2 diffusion inside leaves? Dissecting the diffusion path with Arabidopsis mutants. Human induced increase in atmospheric carbon dioxide is now generally accepted as contributing to global warming. Forecasting our future impact relies on models of terrestrial photosynthesis which use a signature in the atmosphere created by plants when they discriminate against the heavy stable isotope of carbon during photosynthesis. Discrimination between isotopes is affected by carbon dioxide dif ....What limits CO2 diffusion inside leaves? Dissecting the diffusion path with Arabidopsis mutants. Human induced increase in atmospheric carbon dioxide is now generally accepted as contributing to global warming. Forecasting our future impact relies on models of terrestrial photosynthesis which use a signature in the atmosphere created by plants when they discriminate against the heavy stable isotope of carbon during photosynthesis. Discrimination between isotopes is affected by carbon dioxide diffusion within leaves and key steps in this process will be identified through the use of Arabidopsis mutants. Better representation of this process in models will improve estimates of terrestrial photosynthesis and climate change forecastsRead moreRead less
Structure, dynamics and interactions of Plasmodium falciparum merozoite surface protein-2. The solution structure of the merozoite surface protein-2 (MSP-2), from Plasmodium falciparum the causative agent of malaria, will be determined along with an analysis of the motions of residues within the protein. This will allow insights into interactions occurring at the surface coat of the organism, where MSP-2 is a major component. An understanding of how this protein interacts with antibodies of the ....Structure, dynamics and interactions of Plasmodium falciparum merozoite surface protein-2. The solution structure of the merozoite surface protein-2 (MSP-2), from Plasmodium falciparum the causative agent of malaria, will be determined along with an analysis of the motions of residues within the protein. This will allow insights into interactions occurring at the surface coat of the organism, where MSP-2 is a major component. An understanding of how this protein interacts with antibodies of the host's immune system will also be gained. The techniques established during the study of MSP-2 will be useful for the study of larger proteins and protein complexes from many systems in the future.Read moreRead less
Investigating the dynamic nature of antibody stability. The aim of the project is to provide insights into the molecular mechanisms of antibody stability. Monoclonal antibodies have transformed the study of biological processes and represent blockbuster therapeutics for cancer and inflammation. Unfortunately, antibodies often display limited stability, which greatly hinders development. Mutations have recently been identified that render human antibodies resistant to aggregation, and high-resolu ....Investigating the dynamic nature of antibody stability. The aim of the project is to provide insights into the molecular mechanisms of antibody stability. Monoclonal antibodies have transformed the study of biological processes and represent blockbuster therapeutics for cancer and inflammation. Unfortunately, antibodies often display limited stability, which greatly hinders development. Mutations have recently been identified that render human antibodies resistant to aggregation, and high-resolution crystal structures are being used to identify function. Intriguingly, preliminary data indicates that the mutations do not affect the native antibody structure, but rather influence dynamic states. The project plans to use a combination of mutagenesis, molecular dynamics simulation and deuterium exchange to study antibody dynamics.Read moreRead less
Molecular and Cellular Characterisations of the Cortical Actin Cytoskeleton in the Plant Arabidopsis thaliana. Plant cells contain extensive arrays of the cytoskeletal protein actin that attach to the plasma membrane and may play important roles in cell elongation through interactions with cortical microtubules. However, the organisation, dynamics and functions of cortical actin remain poorly understood. I will combine cell and molecular approaches to understanding cortical actin in living tissu ....Molecular and Cellular Characterisations of the Cortical Actin Cytoskeleton in the Plant Arabidopsis thaliana. Plant cells contain extensive arrays of the cytoskeletal protein actin that attach to the plasma membrane and may play important roles in cell elongation through interactions with cortical microtubules. However, the organisation, dynamics and functions of cortical actin remain poorly understood. I will combine cell and molecular approaches to understanding cortical actin in living tissue of Arabidopsis, using both wild-type and previously uncharacterised mutants, and will develop a novel mutational screening strategy to isolate mutants disrupted in plasma membrane or microtubule binding. This research will contribute significantly to a greater understanding of how the plant grows and develops.Read moreRead less
Structural studies of a reconstructed primordial antigen receptor. Antigen receptors (B- and T-cell receptor) form the basis of the adaptive immune system of humans and all other modern day vertebrates. These complex receptors are believed to have evolved from an extinct homodimeric (symmetrical) ancestor through a process of gene duplication and diversification. However, any molecular insights had so far remained elusive. Using laboratory evolution and X-ray crystallography this project demonst ....Structural studies of a reconstructed primordial antigen receptor. Antigen receptors (B- and T-cell receptor) form the basis of the adaptive immune system of humans and all other modern day vertebrates. These complex receptors are believed to have evolved from an extinct homodimeric (symmetrical) ancestor through a process of gene duplication and diversification. However, any molecular insights had so far remained elusive. Using laboratory evolution and X-ray crystallography this project demonstrates that such a primordial receptor can in principle be reconstructed and characterised. The project proposes to expand this work, which will provide intriguing insights into antigen receptor evolution. The reconstruction of basic recognition modules will also be highly beneficial for biosensor applications. Read moreRead less
Phloem unloading of sucrose: cloning, functional characterisation and regulation of novel membrane transporters. Sucrose is the principal form in which plant biomass, produced in photosynthetic leaves, is transported to non-photosynthetic organs for growth and storage. Sucrose transport proteins play pivotal roles in facilitating sucrose transport around plants. Hence activities of sucrose transporters directly impact on plant growth rates and crop yields. Our aim is to isolate hitherto unkno ....Phloem unloading of sucrose: cloning, functional characterisation and regulation of novel membrane transporters. Sucrose is the principal form in which plant biomass, produced in photosynthetic leaves, is transported to non-photosynthetic organs for growth and storage. Sucrose transport proteins play pivotal roles in facilitating sucrose transport around plants. Hence activities of sucrose transporters directly impact on plant growth rates and crop yields. Our aim is to isolate hitherto unknown membrane proteins that move sucrose at high rates between cells and discover their transport properties. Expected outcomes are to better understand mechanisms and regulation of sucrose transport and hence provide novel opportunities to enhance crop yield. The project will foster a productive international collaboration.Read moreRead less
Multifunctional channels as key components of biotrophic interfaces in legumes. In legumes there are two types of membrane interfaces between different genomes that are critical for growth and yield (nitrogen fixation and seed loading), which require cell-signalling pathways to control nutrient exchange. The membranes of these interfaces contain specialised proteins that form multifunctional channels through which water, uncharged molecules and electrolytes move. These channels are likely to be ....Multifunctional channels as key components of biotrophic interfaces in legumes. In legumes there are two types of membrane interfaces between different genomes that are critical for growth and yield (nitrogen fixation and seed loading), which require cell-signalling pathways to control nutrient exchange. The membranes of these interfaces contain specialised proteins that form multifunctional channels through which water, uncharged molecules and electrolytes move. These channels are likely to be responsible for supporting the bulk of transported nutrients and in controlling their exchange. We aim to discover how these channels function in nitrogen fixation and seed loading with a view to developing new technologies that may enhance crop productivity.Read moreRead less