The structural basis of cell surface receptor signalling mechanisms.

细胞表面受体信号传导机制的结构基础。

• 批准号: G0900084-E01/1
• 负责人: Yvonne Jones
• 金额: $ 188.28万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0900084-E01%2F1
• 关键词: structural; basis; cell; surface; receptor

The cells of a multicellular organism, such as a human, must be subject to an exquisite choreography during development. Each cell must achieve the particular balance between adhesion and motility appropriate to its role at a specific time and place in the developing organism. Much of the information to direct each cell must be garnered through interaction with its immediate environment including neighbouring cells. These interactions are mediated by various types of receptor molecules embedded in the cell surface. We wish to understand how sets of receptors work together to control the ability of a cell to stick (adhere) or to move in a specific direction. Using the techniques of structural biology we aim to show in atomic detail the mechanisms by which receptors control cell adhesion and guidance, for example in a system which directs the wiring of the brain. These mechanisms must integrate receptor interactions occurring between cells and on the same cell surface, as well as spanning from the extracellular to the intracellular environment. To generate insight into such systems we will need to use state of the art techniques developed during our previous MRC funded studies to produce suitable samples of membrane spanning receptors and complexes and to combine in vitro structural studies on the isolated molecules with in situ analyses in the functionally relevant context of the cell surface. Ultimately it may prove possible to exploit the mechanisms we reveal to repair nerve damage or to treat various neurological disorders.

多细胞生物（如人类）的细胞在发育过程中必须经过精心设计。每个细胞都必须在黏附性和运动性之间达到特定的平衡，以适应其在发育生物体中的特定时间和地点的作用。指导每个细胞的大部分信息必须通过与其直接环境（包括邻近细胞）的相互作用来获得。这些相互作用是由嵌入细胞表面的各种类型的受体分子介导的。我们希望了解一组受体如何协同工作来控制细胞粘附或向特定方向移动的能力。利用结构生物学的技术，我们的目标是在原子细节上展示受体控制细胞粘附和引导的机制，例如在指导大脑线路的系统中。这些机制必须整合发生在细胞之间和同一细胞表面上的受体相互作用，以及从细胞外到细胞内环境的跨越。为了深入了解这些系统，我们需要使用在之前MRC资助的研究中开发的最先进的技术来生产合适的跨膜受体和复合物样品，并将分离分子的体外结构研究与细胞表面功能相关背景下的原位分析相结合。最终，利用我们揭示的机制来修复神经损伤或治疗各种神经系统疾病可能被证明是可能的。