Efficiency and fidelity in mitotic spindle assembly

有丝分裂纺锤体组装的效率和保真度

• 批准号: 9892661
• 负责人: Alexey L Khodjakov
• 金额: $ 25万
• 依托单位: WADSWORTH CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9892661
• 关键词: Behavior; Cell division; Cells; Chromosome Segregation; Chromosomes; Color; Disease; Electron Microscopy; Ensure; Equilibrium; Funding; Genetic Materials; Goals; Grant; Image; Individual; Kinetochores; Label; Laboratories; Lasers; Malignant Neoplasms; Microsurgery; Microtubules; Mitosis; Mitotic spindle; Molecular; Molecular Machines; Organelles; Parents; Research; Route; Testing; United States National Institutes of Health; Work; cell transformation; chromosome missegregation; chromosome movement; daughter cell; design; genetic information; insight; operation; organizational structure; parent grant; sample fixation

The goal of cell division (mitosis) is to partition genetic information, in the form of chromosomes, equally into the two daughter cells. The overarching goal of our research is to reveal the mechanisms that allow the spindle to assemble rapidly and with minimal number of errors. Our previous work demonstrates that every major step in spindle assembly can be reached via several alternative routes. This multiplicity of alternative mechanisms prompts the hypothesis that a proper balance in the contributions from individual mechanisms must be maintained to ensure error-free chromosome segregation. The goal of the parent 1 R35 GM130298-01 (Efficiency and fidelity in mitotic spindle assembly) is to test this hypothesis by quantitatively characterizing spindle assembly in normal vs. chromosomally instable (CIN) cells that frequently mis-segregate their chromosomes. Towards this goal, we identify and characterize molecular mechanisms that govern attachment of chromosomes to microtubules of the mitotic `spindle' via sophisticated imaging such as laser microsurgery, precise tracking of chromosome movements, and correlative electron-microscopy analyses conducted on the kinetochores whose behavior was followed in live cells up to the moment of fixation. These approaches rely on a laser microirradiation workstation, designed, assembled, and maintained in the PI's laboratory with support from the NIH grants and funds contributed by the Wadsworth Center. This application seeks to obtain funds for upgrading the workstation to enable laser operations in cells with various organelles labeled in different colors. Multi-color capabilities will vastly accelerate our scientific progress towards the goals of the parent grant and will also facilitate several collaborative studies supported by NIH GMS grants.

细胞分裂（有丝分裂）的目的是将染色体形式的遗传信息均匀地分割成染色体