Structural Basis of Molecular Mechanisms in Cell Guidance and Adhesion.

点击翻译按钮获取中文摘要

The cells of a multicellular organism, such as a human, are 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 one family of molecules, the semaphorins, work together with their receptors, the plexins, 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 uncover, in atomic detail, the mechanisms by which the semaphorins and plexins control cell adhesion and guidance, for example in directing 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 to produce suitable samples of the semaphorins, the plexins and their 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. This is basic research into the mechanisms by which biology works to build the nervous system and the blood vessels, to maintain bones and to activate the immune system. By understanding these mechanisms we will also be better equipped to explore molecular factors which may contribute to the failure of severed nerves to regenerate following spinal cord injury, to bone-related disorders, for example osteoporosis, to neurodevelopmental disorders such as autism disorder spectrum, and to cancer. Ultimately this knowledge can be used by the biotechnology and pharmaceutical industries, to inform and guide the design of novel therapeutics.