Regulation of FtsZ-ring Assembly in E. Coli Cytokinesis

大肠杆菌胞质分裂中 FtsZ 环组装的调控

• 批准号: 1158059
• 负责人: Anuradha Janakiraman
• 金额: $ 59.94万
• 依托单位: CUNY City College
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1158059&HistoricalAwards=false
• 关键词: Regulation; FtsZ; ring; Assembly; E.

Intellectual MeritUsing the bacterium E. coli as a model system, this study addresses the fundamental scientific problem of how cells divide. In a key step, the essential protein FtsZ forms a cytoskeletal ring structure at midcell that establishes the site of division and provides a structural framework for the localization of a multi-protein "molecular machine" that promotes division in bacteria. FtsZ is an ancient protein that is found in most bacteria, some archaea, all chloroplasts, and in primitive mitochondria. A number of proteins interact directly with FtsZ and regulate FtsZ polymer assembly/disassembly at midcell ensuring the spatial and temporal integrity of bacterial cell division. The molecular nature of the diverse protein-protein interactions that regulate the assembly of FtsZ during early stages of division are not yet well understood. Therefore, the identification of the full complement of FtsZ regulatory proteins and their interactions with FtsZ will greatly aid in developing a comprehensive understanding of FtsZ structure and assembly dynamics in the cell. The present project focuses on two newly identified FtsZ-associated proteins (Zap) in E. coli and their molecular interactions with FtsZ. The Zap proteins are conserved in a number of related bacterial species. An analysis of FtsZ-Zap interactions to atomic or near atomic precision in the genetically tractable E. coli will enhance the understanding of the complex interplay between FtsZ and its associated proteins in other bacterial species. More broadly, this research is also expected to further our understanding of fundamental aspects of bacterial cell biology.Broader ImpactsAs the only research laboratory at City College of New York with an emphasis in prokaryotic biology, a field with important implications in the understanding of fundamental cellular processes required by all organisms, this project will form a basis for innovative curriculum development in the classroom, as well as research training for graduate and undergraduate students. Mentoring of City College students, many of whom are minority and/or female, through successful research projects contributes to nationwide efforts to encourage members of underrepresented groups to choose and succeed in research careers. To specifically generate excitement about microbial processes among younger students, members of the research laboratory will continue to participate in several community outreach initiatives in City College's upper Manhattan neighborhood. These efforts include involvement in a local middle school science club and the summer College Now program, a free CUNY initiative to support high school students' early interest in science, improve their science preparation for college, and inspire them to make college science study an attainable goal.

本研究以大肠杆菌为模型系统，解决了细胞如何分裂的基本科学问题。在一个关键步骤中，必需蛋白FtsZ在中间细胞形成细胞骨架环结构，建立分裂位点，并为促进细菌分裂的多蛋白“分子机器”的定位提供结构框架。FtsZ是一种古老的蛋白质，存在于大多数细菌、一些古细菌、所有叶绿体和原始线粒体中。许多蛋白质直接与FtsZ相互作用，并调节FtsZ聚合物在细胞中间的组装/拆卸，确保细菌细胞分裂的时空完整性。在分裂的早期阶段，调节FtsZ组装的各种蛋白质-蛋白质相互作用的分子性质尚未得到很好的理解。因此，鉴定完整的FtsZ调节蛋白及其与FtsZ的相互作用将极大地有助于全面了解FtsZ在细胞中的结构和组装动力学。本项目重点研究了大肠杆菌中两个新发现的FtsZ相关蛋白（Zap）及其与FtsZ的分子相互作用。Zap蛋白在许多相关的细菌物种中是保守的。对FtsZ- zap在遗传易处理的大肠杆菌中原子或接近原子精度的相互作用进行分析，将增强对FtsZ及其相关蛋白在其他细菌物种中复杂相互作用的理解。更广泛地说，这项研究也有望进一步加深我们对细菌细胞生物学基本方面的理解。更广泛的影响作为纽约城市学院唯一一个以原核生物为重点的研究实验室，这一领域对理解所有生物体所需的基本细胞过程具有重要意义，该项目将为课堂上的创新课程开发以及研究生和本科生的研究培训奠定基础。指导城市学院的学生，其中许多是少数民族和/或女性，通过成功的研究项目有助于全国范围内的努力，鼓励代表性不足的群体的成员选择并在研究事业中取得成功。为了在年轻学生中引起对微生物过程的兴趣，研究实验室的成员将继续参与城市学院曼哈顿上城区的几个社区外展活动。这些努力包括参与当地的一个中学科学俱乐部和“现在就上大学”暑期项目，这是一项免费的城市大学倡议，旨在支持高中生早期对科学的兴趣，改善他们对大学的科学准备，并激励他们将大学科学学习作为一个可实现的目标。