The Yeast Centrosome - Structure Assembly & Function

酵母中心体 - 结构组装

基本信息

批准号：
8668219
负责人：
MARK WINEY
金额：
$ 146.06万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8668219
关键词：
Address Alleles Architecture Cell Cycle Cells Centrosome Chromosome Segregation Chromosome abnormality Chromosomes Collaborations Colorado Complex Data Defect Developmental Delay Disorders Disease Environment Event Fluorescence Resonance Energy Transfer Future Genomic Instability Goals Grant Homeostasis Human In Situ In Vitro Individual Knowledge Lead Learning Malignant Neoplasms Maps Measures Mechanics Microtubule-Organizing Center Microtubules Mitosis Mitotic Chromosome Mitotic spindle Modeling Molecular Organelles Principal Investigator Program Research Project Grants Property Proteins Recruitment Activity Regulation Research Research Personnel Resources Roentgen Rays Rupture Saccharomyces cerevisiae Site Structural Biologist Structural Models Structure Testing Tubulin Vertebrates Washington Wisconsin Work Yeasts biophysical techniques chromosome movement electron tomography flexibility in vivo interdisciplinary approach interest metaplastic cell transformation mutant nervous system disorder public health relevance spindle pole body

项目摘要

DESCRIPTION (provided by applicant): Grant (PPG) will create a collaborative environment to coordinate research on centrosome structure, mechanics, homeostasis and function. Six investigators will study the Saccharomyces cerevisiae centrosome as a model microtubule-organizing center (MTOC) analogous to the vertebrate centrosome, which shares key homologous components and regulators. A centrosome/SPB is the primary microtubule-organizing center of the cell and is critical for bipolar spindle assembly and accurate mitotic chromosome segregation. Centrosome duplication is an essential cell cycle event being the first step in spindle formation; defects in duplication or function lead to genomic instability and cellular transformation. Accurate chromosome segregation depends on both proper regulation of spindle assembly and precise connections between spindle microtubules and chromosomes. The PPG is focused specifically on 10 core SPB components that form the lattice and microtubule nucleation sites including the y-tubulin complexes. These proteins act similarly to the pericentriolar material of vertebrate centrosomes, which is crucial for microtubule nucleation and organization, but poorly understood. We propose to elucidate the molecular architecture of the yeast centrosome and to probe the mechanisms, by which it is assembled, maintained and functions in nucleating microtubules. A multidisciplinary approach examining different aspects of the problem will be coordinated to include: determining how the structure and mechanics of the y-tubulin complex and associated proteins collaborate to accomplish microtubule nucleation; investigating how core SPB components are assembled and how they recruit y-tubulin complexes; identifying the critical intrinsic and extrinsic factors for maintaining homeostasis of this dynamic organelle; solving the atomic structure of SPB components and complexes, and working toward an integrated structural model of the entire SPB core. This PPG builds on existing collaborations between David Agard (UCSF) and Trisha Davis (U. Washington) on g- tubulin complexes, and Ivan Rayment (U. Wisconsin) and Mark Winey (U. Colorado) on core SPB components. These four groups will work together on the 10 proteins. Their projects will profit from structural modeling of the SPB (Andrej Sali, UCSF) and quantifying the mechanical properties of the SPB using biophysical techniques (Chip Asbury, U. Washington). There is tremendous potential to produce an unprecedented molecular description of a centrosome revealing mechanisms of assembly, stability and function. This work will serve as a model for future analysis of the much more complex human centrosome.

描述（由申请人提供）：Grant（PPG）将创建一个协作环境，以协调有关中心体结构，力学，体内稳态和功能的研究。六名研究人员将研究酿酒酵母中心体作为模型微管 - 组织中心（MTOC）类似于脊椎动物中心体，该中心体共享关键的同源组件和调节剂。中心体/SPB是细胞的主要微管组织中心，对于双极纺锤体组件和准确的有丝分裂染色体分离至关重要。中心体重复是必不可少的细胞周期事件，是纺锤体形成的第一步。重复或功能的缺陷导致基因组不稳定性和细胞转化。准确的染色体分离取决于纺锤体组件的适当调节，以及纺锤微管与染色体之间的精确连接。 PPG专门集中在10个核心SPB组件上，它们形成了晶格和微管成核位点，包括Y微管蛋白复合物。这些蛋白质的作用类似于脊椎动物中心体的周围三元素物质，脊椎动物中心体对于微管成核和组织至关重要，但知识较低。我们建议阐明酵母中心体的分子结构，并探测其组装，维护并在成核微管中起作用的机制。研究问题的不同方面的多学科方法将被协调，包括：确定Y-微管蛋白复合物和相关蛋白的结构和力学如何协作以完成微管成核；研究核心SPB组件的组装方式以及它们如何募集Y-微管蛋白复合物；确定维持这种动态细胞器的稳态的关键内在和外在因素；求解SPB组件和复合物的原子结构，并朝着整个SPB核心的综合结构模型致力于。该PPG建立在David Agard（UCSF）和Trisha Davis（U. Washington）与G-微管蛋白配合物以及伊万·雷蒙特（Ivan Rayment）（U. Wisconsin）和Mark Winey（U.Colorado）上的现有合作基础上。这四组将在10种蛋白质上共同努力。他们的项目将从SPB（Andrej Sali，UCSF）的结构建模中获利，并使用生物物理技术（Chip Asbury，U. Washington）量化SPB的机械性能。产生对集中，稳定性和功能的中心体揭示机制的前所未有的分子描述具有巨大的潜力。这项工作将作为对更复杂的人类中心体的将来分析的模型。