2007 NIH Director's Pioneer Award Program (DP1)

2007 NIH 院长先锋奖计划 (DP1)

基本信息

批准号：
7936092
负责人：
Margaret Lise Gardel
金额：
$ 76.75万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-30 至 2012-07-31
项目状态：
已结题

项目摘要

A major challenge in cell and organism biology is to understand how living cell physiology emerges from the biophysical properties of individual macromolecules. The morphological and physical behaviors of cells required for cell adhesion, migration and division depend on the proper spatial and temporal regulation of a vast hierarchy of multi-protein machines, called the cytoskeleton. However, while we are gaining increasing amounts of knowledge of properties of individual cytoskeletal proteins, we have very little knowledge about the self-assembly and physical properties of multi-protein assemblies that form physical structures to transmit mechanical information up to cellular length scales. For example, we do not understand how forces generated by individual molecular motors are exploited by cytoskeletal assemblies to regulate morphogenesis and force generation at the cellular level. Current understanding of the physical behavior of the cellular cytoskeleton has been limited both by the lack of experimental techniques to probe the dynamic structure and physical properties of mesoscopic cytoskeletal assemblies in living cells. I propose to establish the experimental tools to study the biophysical properties of cytoskeletal matter in living cells by integrating approaches from condensed matter physics with molecular cell biology. This work will identify the underlying physics of emergent cytoskeletal assemblies and will provide predictive analytical models to link our understanding of the biophysics of molecules to cell behaviors. Finally, this work will impact the treatment of diseases that are a result of misregulation of the physical behaviors of cells, including cancer metastasis and cardiac diseases.

细胞和生物体生物学的一个主要挑战是了解活细胞生理学如何来自单个大分子的生物物理特性。形态和细胞粘附、迁移和分裂所需的细胞物理行为取决于适当的一个巨大的多蛋白质机器层次结构（称为细胞骨架）的空间和时间调节。然而，尽管我们对个人财产的了解越来越多对于细胞骨架蛋白，我们对其自组装和物理特性知之甚少形成物理结构以将机械信息传递到细胞的多蛋白质组装体长度尺度。例如，我们不了解单个分子如何产生力细胞骨架组件利用马达来调节形态发生和力的产生细胞水平。目前对细胞骨架物理行为的理解由于缺乏探测动态结构和物理的实验技术而受到限制活细胞中细观细胞骨架组件的特性。我提议设立研究活细胞中细胞骨架物质的生物物理特性的实验工具将凝聚态物理学与分子细胞生物学的方法相结合。这项工作将确定新兴细胞骨架组装的基本物理原理，并将提供预测将我们对分子生物物理学的理解与细胞行为联系起来的分析模型。最后，这项工作将影响因身体调节不当而导致的疾病的治疗细胞的行为，包括癌症转移和心脏病。