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.

该项目的主要目标是了解钙粘蛋白介导的细胞间粘附的分子基础。钙粘蛋白是位于许多细胞表面的分子家族。当相似的细胞接触时，它们会相互粘附，而不同类型的细胞则倾向于分离。这一关键特性允许体内不同组织形成并相互分离，可以追溯到单个钙粘蛋白分子的分子特性。但不同的钙粘蛋白家族成员都彼此相似。什么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，将对野生型和设计的突变型钙粘蛋白进行结合亲和力，目的是以受控方式改变它们的行为。实验工作将基于使用理论方法来阐明钙粘蛋白结合的分子基础。 该项目的第二阶段将侧重于将分子与细胞特性联系起来。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就会聚集在一起形成连接。将进行模拟以阐明这是如何发生的，并且根据获得的结果，将开发模拟细胞过程的新理论方法。该研究项目代表了一项涉及理论和实验的综合研究工作，跨越了相当不同的学科，包括分子建模和模拟、结构生物学、溶液生物物理学和细胞生物学。该项目本质上是多尺度和跨学科的，并且正在实施的战略所开发的可以作为其他此类努力的模型，将计算方法整合到现代生物学的前沿领域。该项目的一个特别重要的要素是培养在计算和实验工作方面具有专业知识的科学家，包括具有不同背景的高级研究人员的联合指导。对女性和少数族裔科学家的培训是研究的一个组成部分。该实验室参加了 HHMI 组织的 EXROP（特殊研究机会）计划，并在此背景下每年夏天接待少数族裔本科生。在实验室接受培训的本科生和研究生都已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部生物分子系统和细胞系统集群共同支持。