Molecular Genetic Analysis of Regulatory Networks Governing Cytokinesis

细胞分裂调控网络的分子遗传学分析

• 批准号: RGPIN-2014-03944
• 负责人: Karagiannis, Jim
• 金额: $ 2.55万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=587508
• 关键词: Molecular; Genetic; Analysis; Regulatory; Networks

Research within the lab focuses on the regulatory networks required to bring about the successful completion of cytokinesis in the model eukaryote, Schizosaccharomyces pombe. While previous work in the field has centered on the cytoskeletal structures and forces required to bring about cell cleavage, our goals are to better understand the genetic regulatory networks required for cytokinesis to occur faithfully, at the proper location, and at the proper time during the cell cycle. The foundation of the current proposal stems from recent work supporting the existence of a cytokinesis "monitoring system". Upon perturbation of the cell division machinery, this system has the capacity to both delay cell cycle progression and stabilize the cytokinetic actomyosin ring. The biological importance of such mechanisms have been substantiated in recent years by the demonstration that tetraploid intermediates (produced upon cytokinesis failure) show a markedly increased potential for tumourigenesis. Thus, an understanding of these networks has the potential to provide insight into the mechanisms important for maintaining genomic integrity in eukaryotes. The current proposal revolves around the molecular and genetic analysis of several previously uncharacterized regulatory networks required for the proper function and/or regulation of the cytokinesis monitoring system. These pathways were identified through the execution of a genome-wide screen that assayed fission yeast gene deletion mutants for hypersensitivity to Latrunculin A (an actin depolymerizing drug used as a tool to perturb the cell division machinery). As expected this screen identified many genes with known roles in the regulation of cytoskeletal dynamics and/or cytokinesis. In addition, many other unexpected "hits", identifying genes affecting biological processes such as histone acetylation/de-acetylation and transcriptional control were also identified. Using the lab's established skill in molecular biology, genetic analysis, and live-cell imaging, our objectives are to characterize the identified regulatory complexes in order to provide a comprehensive, genome-wide picture of the genetic regulatory wiring required by a model eukaryotic cell to faithfully and reliably execute cytokinesis.

实验室的研究重点是在真核生物裂糖酵母（Schizosaccharomyces pombe）中成功完成细胞分裂所需的调控网络。虽然该领域之前的工作主要集中在细胞骨架结构和导致细胞分裂所需的力量上，但我们的目标是更好地理解细胞分裂在细胞周期中正确的位置和正确的时间准确发生所需的遗传调控网络。