Molecular Analysis of the Spindle Pole Body

主轴极体的分子分析

基本信息

批准号：
7578904
负责人：
Trisha N. Davis
金额：
$ 44.6万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-07-01 至 2011-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7578904
关键词：
Affect Animal Model Architecture Behavior Cell Cycle Cell Death Cell division Cells Chromosome Segregation Chromosomes Collaborations Complex Computer software Congenital Abnormality Core Protein Eukaryotic Cell Fluorescence Resonance Energy Transfer Funding Genes Genetic Materials Genetic Screening Grant Human In Vitro Insecta Kinetochores Life Measures Microtubule-Organizing Center Microtubules Modeling Molecular Analysis Motor Mutagenesis Mutation Nuclear Pore Organism Period Analysis Phenylalanine Phosphorylation Site Phosphotransferases Plus End of the Microtubule Point Mutation Process Protein Dynamics Proteins Regulation Research Personnel Resolution Role Saccharomyces cerevisiae Serine Structure Testing Time Tubulin Work Yeasts aurora B kinase design human TYRP1 protein in vivo insight interest mathematical model mutant novel particle physical property programs protein complex reconstruction research study spindle pole body tomography tool tumorigenesis yeast protein yeast two hybrid system

项目摘要

DESCRIPTION (provided by applicant): Accurate chromosome segregation is required for propagation of all cells. Errors in this process are implicated in oncogenesis, birth defects and cell death. Crucial to proper partitioning of the chromosomes during cell division is the establishment, arrangement and then breakdown of a bipolar spindle. The aim of this grant is to further understand the structure, assembly and dynamics of the proteins that create and control the organization of the spindle in the model organism Saccharomyces cerevisiae. The microtubule organizing center in yeast is the spindle pole body (SPB). The SPB is a dynamic structure that undergoes remodeling in a cell-cycle specific manner. We have identified proteins involved in the remodeling process and will characterize them. We have provided a detailed architectural description of the SPB and will continue our structural analysis. The SPB nucleates and organizes microtubules. We will perform a set of experiments designed to distinguish between two current models for nucleation. Finally, we have found that kinetochores can biorient without being attached to the plus-end of microtubules. New insights into biorientation will be obtained from determining the role of kinetochores, motors and other spindle proteins in the formation of the bipolar spindle when plus-end attachment is not involved. Because many proteins and spindle features are conserved from yeast to human, our studies will inform models of how eukaryotic cells correctly distribute their genetic material.

描述（由申请人提供）：所有细胞的繁殖都需要准确的染色体分离。这一过程中的错误与肿瘤发生、出生缺陷和细胞死亡有关。细胞分裂过程中染色体正确分配的关键是双极纺锤体的建立、排列和分解。这笔资助的目的是进一步了解在模式生物酿酒酵母中创建和控制纺锤体组织的蛋白质的结构、组装和动力学。酵母中的微管组织中心是纺锤体极体（SPB）。 SPB 是一种动态结构，以细胞周期特定的方式进行重塑。我们已经鉴定了参与重塑过程的蛋白质并将对其进行表征。我们已经提供了 SPB 的详细架构描述，并将继续我们的结构分析。 SPB 使微管成核并组织。我们将进行一组实验，旨在区分当前的两种成核模型。最后，我们发现着丝粒可以生物定向而不附着在微管的正端。当不涉及正端附着时，通过确定动粒、马达和其他纺锤体蛋白在双极纺锤体形成中的作用，可以获得对生物取向的新见解。由于许多蛋白质和纺锤体特征从酵母到人类都是保守的，因此我们的研究将为真核细胞如何正确分配其遗传物质的模型提供信息。