The role of snare-mediated membrane traffic in cell adhesion

细胞黏附是一个复杂的过程，在多细胞生物体中对细胞的生长和分化起着基础性的作用。尤其是细胞黏附对组织和器官内细胞的存活有深远的影响，也可以显著影响许多病理情况。细胞黏附是细胞附着和扩散到细胞外基于蛋白质的结构(细胞外基质)上的过程。这种相互作用会影响细胞的形状、细胞内结构和生化反应以及基因表达。我研究的长期目标是检查专门调节细胞黏附的细胞内分子机制。在这方面，我打算建立一个研究计划，有助于对细胞内这些生物学功能的基本了解。在我的研究计划的长期目标中，本申请中提出的研究包含三个具体目标：1)确定细胞膜重组在细胞黏附过程中所起的作用；2)分析调节细胞黏附所涉及的膜重组的蛋白质，3)识别这些活动的细胞调节因子。我计划研究控制细胞黏附的蛋白质、调节细胞膜重组的蛋白质和调节细胞内部“骨架”(肌动蛋白细胞骨架)的蛋白质的功能。我希望揭示具有这些不同功能的蛋白质如何在细胞内共同控制细胞与细胞外基质的黏附并最终影响细胞行为。这项研究将涉及使用培养的细胞类型、对活细胞进行实验的现代生物技术、高分辨率显微镜和生化分析。总的来说，这些方法将允许直接检查细胞黏附过程中的蛋白质功能，并将产生在细胞生物学和生物化学领域具有广泛意义的结果。

Cell adhesion is a complex process that plays a fundamental role in the growth and differentiation of cells in multicellular organisms.   In particular, cell adhesion has profound influence over the survival of dells within tissues and organs and can also significantly impact many pathological conditions.  Cell adhesion is the process by which cells attach and spread on protein-based structures outside the cell (the extracellular matrix).  Such interactions affect cell shape, intracellular structures and biochemical reactions and gene expression.  The long-term goals of my research are to examine the intracellular, molecular machinery that specifically regulates cell adhesion.  In doing this, I intend to establish a research program that will contribute to the basic understanding of these biological functions within cells.Within the long-term goals of my research program, the research proposed in this application contains three specific aims: 1) to define the role that restructuring of cell membranes plays in the processes of cell adhesion; 2) to analyse proteins which function to regulate the membrane restructuring that is involved in cell adhesion and 3) identify cellular regulators of these activities.  I plan to examine the functions of proteins that control cell adhesion, proteins that regulate the restructuring of cell membranes and proteins that regulate the cell's internal "skeleton" (the actin cytoskeleton).  I expect to uncover how proteins with these diverse functions work together within cells to control cell adhesion to the extracellular matrix and ultimately affect cell behaviour.  This research will involve the use of cultured cell types, modern biological techniques to perform experiments on living cells, high-resolution microscopy and biochemical analyses. Collectively, these approaches will allow the direct examination of protein function during cell adhesion and will yield results that hold wide significance in the disciplines of cell biology and biochemistry.