Modular protein design for spatial control and organisation

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Proteins perform most of the functions in biological systems, from structural support, to movement, communication and catalysis. Modular protein structures designed to have specific geometric, spatial and conformational properties could be applied to solve problems relating to several fields of research, from biocomposites to cell culture, and this project will aim to explore the possibilities of several of these.Computational protein design of these proteins will be done using mainly the Rosetta modelling suite (www.rosettacommons.org) and the Elfin package (https://github.com/joy13975/elfin) developed by the Parmeggiani Lab. This research will combine protein modelling with structural biology and functional assays, going from design concepts to experimental validation.Initially the work will focus on the computational design and experimental validation of several novel modular protein structures built from the existing database of repeat protein units available. These designs will be developed towards two major areas of interest, as ligand display scaffolds for stem cell culture, and as auxetic protein units for use in biocomposite applications.Two key areas of exploration -- Design of auxetic structures and possible larger assemblies of these units, and investigation of their ability as interstitial strengtheners in natural fibre composites, alongside several other possible uses within composite materials. This work will be in collaboration with the group of Prof Fabrizio Scarpa (Engineering, University of Bristol).- Design of ligand display scaffolds for use in artificial stem cell culture environments. The ability to control receptor activation in stem cell culture via these organised ligand display scaffolds could improve stem cell culture methods and reduce costs associated with ligand internalisation. Functional assays will be performed in collaboration with the group of Dr Ashley Toye (Biochemistry, University of Bristol).This work will also incorporate the development of a computational design pipeline for the efficient production of these larger organised modular protein structures, which will prove a useful tool in the efficient design of future proteins for applications with varying spatial organisations.