Molecular Mechanisms Controlling Adhesion Dynamics During Cell Migration

细胞迁移是许多基本生物过程的核心，如组织组织、神经发育、伤口愈合和免疫反应。从细胞成分的生化分析和细胞动力学和迁移速度的全局测量中，我们了解了许多关于细胞迁移的知识。然而，到目前为止，调控细胞迁移的分子机制还没有得到很好的理解。造成这种情况的主要原因是，研究人员普遍缺乏现成的技术来研究活细胞内的分子动力学和相互作用。我的研究项目侧重于先进的光学显微镜技术的开发和应用，这些技术可以测量完整的、活的、迁移的细胞中的分子动力学和相互作用。为了沿着一个表面移动，细胞必须在它们所移动的基底上形成粘附斑块。这些贴片必须具有足够的粘性或强度，以便细胞产生牵引力并移动，但又不能强到细胞根本无法移动。因此，需要严格控制这些黏附在何时何地形成和分解，这样细胞才能向前推进。我将把先进的光学显微镜技术应用到一些关键分子上，这些分子似乎就像开关一样，控制着细胞何时快速移动，何时形成大的粘连并停止移动。我将研究这些分子并确定它们调节细胞运动的机制。我们发现的分子细节将导致新的和更精细的细胞迁移是如何调节的模型。我开发的先进显微镜工具将有助于其他领域的研究人员研究各种生物过程的分子机制。

Cell migration is central to many fundamental biological processes such as tissue organization, neural development, wound healing and the immune response. Much that is known about cell migration has been learned from biochemical assays on cellular components and global measurements on cellular dynamics and migration speeds. However, to date the molecular mechanisms that regulate cell migration are not well understood. The main reason for this is that there has been a general lack of technologies readily available for researchers to study molecular dynamics and interactions within living cells. My research program focuses on the development and application of advance light microscopy technologies that can measure molecular dynamics and interactions in intact, living, migrating cells.In order to move along a surface, cells must create adhesive patches on the substrate they are moving over. These patches have to be sticky or strong enough for the cell to generate traction and move, but not so strong that the cell cannot move at all. Therefore, there needs to be a tight control on when and where these adhesions form and disassemble so the cell can advance forward. I will apply advanced light microscopy techniques to some of the key molecules that appear to be acting as switches controlling when cells move quickly and when they form large adhesions and stop moving. I will look at these molecules and determine the mechanisms they use to regulate cell movement.The molecular details we uncover will lead to new and more refined models of how cell migration is regulated. The advanced microscopy tools I develop will be useful to researchers in other fields studying the molecular mechanism of diverse biological processes.