The structural basis of cell surface receptor signalling mechanisms.

点击翻译按钮获取中文摘要

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.