Modular protein design for spatial control and organisation

用于空间控制和组织的模块化蛋白质设计

• 批准号: 2268856
• 金额: --
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2268856
• 关键词: Modular; protein; design; spatial; control

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.

蛋白质在生物系统中执行大部分功能，从结构支持到运动，通信和催化。设计具有特定几何、空间和构象特性的模块化蛋白质结构可以应用于解决从生物复合材料到细胞培养等多个研究领域的相关问题，本项目旨在探索其中几种可能性。这些蛋白质的计算蛋白质设计将主要使用Rosetta建模套件（www.rosettacommons.org）和Parmeggiani实验室开发的Elfin软件包（https：//github.com/joy13975/elfin）完成。本研究将联合收割机蛋白质建模与结构生物学和功能分析相结合，从设计概念到实验验证，最初的工作将集中在从现有的重复蛋白质单元数据库中构建的几种新型模块化蛋白质结构的计算设计和实验验证。这些设计将朝着两个主要领域发展，作为干细胞培养的配体展示支架，以及作为用于生物复合材料应用的拉胀蛋白单元。两个关键的探索领域--拉胀结构的设计和这些单元的可能的更大组件，以及研究它们作为天然纤维复合材料中的间隙增强剂的能力，以及复合材料中的其他几种可能的用途。这项工作将与Fabrizio Scarpa教授（工程，布里斯托大学）的团队合作。用于人工干细胞培养环境的配体展示支架的设计。通过这些有组织的配体展示支架控制干细胞培养中受体活化的能力可以改善干细胞培养方法并降低与配体内化相关的成本。功能分析将与阿什利托耶博士（生物化学，布里斯托大学）的小组合作进行。这项工作还将包括一个计算设计管道的发展，这些更大的组织模块化蛋白质结构的有效生产，这将证明是一个有用的工具，在未来的蛋白质的有效设计与不同的空间组织的应用。