The Molecular Basis of Cadherin-Mediated Cell Adhesion

钙粘蛋白介导的细胞粘附的分子基础

• 批准号: 0918535
• 负责人: Barry Honig
• 金额: $ 101.84万
• 依托单位: Columbia University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0918535&HistoricalAwards=false
• 关键词: Molecular; Basis; Cadherin; Mediated; Cell

The main objective of this project is to understand the molecular basis of cadherin-mediated cell-cell adhesion. Cadherins are a family of molecules that are located on the surfaces of many cells. When like cells come in contact they adhere to one another whereas cells of different types tend to separate. This crucial property, which allows different tissues in the body to form and to separate from one another, can be traced to the molecular properties of individual cadherin molecules. But different cadherin family members are all similar to one another. What mechanisms allow small molecular differences to mediate highly specific cellular behavior? To address these questions, binding affinities of wild type and designed mutant cadherins will be carried out with the goal of modifying their behavior in controlled ways. The experimental work will be based on the use of theoretical methods that will elucidate the molecular basis of cadherin binding. The second stage of the project will focus on relating molecular to cellular properties. Once cells containing cadherins begin to adhere, the cadherins on each cell tend to cluster together to form junctions. Simulations will be carried out to clarify how this occurs and, based on the results that are obtained, new theoretical methods to simulate cellular processes will be developed. This research project represents an integrated research effort involving both theory and experiment and spans quite diverse disciplines including molecular modeling and simulation, structural biology, solution biophysics, and cell biology.The project is multi-scale and interdisciplinary in nature and the strategy that is being developed can serve as a model for other such efforts that integrate computational methods in cutting edge areas of modern biology. A particularly important element of the project is the development of scientists with expertise in both computational and experimental work including joint mentoring from senior researchers with very different backgrounds. The training of women and minority scientists is an integral component of the research. The lab participates in the EXROP (Exceptional Research Opportunities) program organized by HHMI and, in this context, hosts minority undergraduate students each summer. Both undergraduate and graduate minority students trained in the lab have become highly successful research scientists.This project is jointly supported by the Biomolecular Systems and Cellular Systems Clusters in the Division of Molecular and Cellular Biosciences.

该项目的主要目的是了解钙粘蛋白介导的细胞粘附的分子基础。钙粘蛋白是位于许多细胞表面上的分子家族。当类似的细胞接触时，它们会彼此粘附，而不同类型的细胞往往会分离。这种至关重要的特性允许体内的不同组织形成并彼此分离，可以追溯到单个钙粘蛋白分子的分子特性。但是不同的cadherin家族成员彼此相似。哪些机制允许小分子差异介导高度特异性的细胞行为？为了解决这些问题，将实现野生型和设计突变核蛋白的结合亲密关系，目的是以受控方式修改其行为。实验工作将基于使用理论方法的使用，该方法将阐明钙粘蛋白结合的分子基础。 该项目的第二阶段将集中于将分子与细胞特性有关。一旦含有钙粘蛋白的细胞开始粘附，每个细胞上的钙粘蛋白倾向于聚集在一起形成连接。将进行模拟以阐明发生这种情况的方式，并基于获得的结果，将开发出新的模拟细胞过程的理论方法。该研究项目代表了一项涉及理论和实验的综合研究工作，并且涵盖了相当多样化的学科，包括分子建模和仿真，结构生物学，溶液生物物理学和细胞生物学。该项目是自然界的多尺度和跨学科的，并且正在开发的策略可以用作在现代生物学中融合现代生物学的其他努力的模型。该项目的一个特别重要的要素是在计算和实验工作中具有专业知识的科学家的发展，包括来自具有不同背景的高级研究人员的共同指导。培训妇女和少数民族科学家是研究的组成部分。该实验室参加了由HHMI组织的EXROP（杰出研究机会）计划，在这种情况下，每年夏天都会主办少数族裔本科生。在实验室培训的本科生和研究生少数族裔学生都已经成为非常成功的研究科学家。该项目由分子和细胞生物科学分类的生物分子系统和细胞系统群集共同支持。