Electron Microscopy of Biological Macromolecules

描述（由申请人提供）：本计划项目代表了一个协调和相互支持的努力，以追求结构生物学的研究，其中电子衍射和电子显微镜起着关键作用，并推进技术，使这项研究成为可能。该计划中的三个项目代表了电子晶体学和显微镜方法的应用，以及该计划支持的仪器，以解决结构生物学中的具体问题。这些应用集中在真核细胞骨架的各个方面，包括：（项目A）微管蛋白的结构及其与影响微管细胞骨架功能的配体和其他蛋白质的相互作用的研究；（项目B）内耳内将声音转化为神经信号和控制听觉灵敏度的装置的研究；（项目C）研究细胞分裂过程中连接微管和染色体并确保染色体正确分离的蛋白质。此外，单独资助的研究项目在较小程度上依赖于计划项目支持的设备和设施，也被列入准成员项目。行政核心（D计划）维护主要设备，支持计算机资源，继续努力提高电子显微镜数据的质量和吞吐量，并为计划项目的所有参与者提供一种知识社区和共同身份感。

DESCRIPTION (provided by applicant): This Program Project represents a coordinated and mutually supporting effort to pursue research in structural biology where electron diffraction and electron microscopy play a key role and to advance the technology that enables this research. Three projects within the Program represent applications of the methods of electron crystallography and microscopy, as well as of the instrumentation supported by the Program, to specific problems in structural biology. These applications focus on aspects of the eukaryotic cytoskeleton and include: (Project A) Studies of the structure of tubulin and its interactions with ligands and other proteins that affect the function of the microtubule cytoskeleton; (Project B) Studies of the apparatus in the inner ear that converts sound to nerve signals and controls sensitivity of hearing; (Project C) Studies of the proteins that connect microtubules to chromosomes and ensure proper chromosome segregation during cell division. Additional, separately funded research projects which rely to a smaller extent on equipment and facilities supported by the Program Project are also included as Associate member projects. The Administrative Core (Project D) maintains the major equipment, supports computer resources, continues our efforts to improve the quality and throughput of electron microscopy data, and provides a sense of intellectual community and common identity for all the participants in the Program Project. PUBLIC HEALTH RELEVANCE: Our structural studies of several medically important protein complexes that play essential roles within the cell provide the basis for understanding their normal function as well as failures in these functions that are associated with disease and birth defects.