Molecular mechanisms of bacterial cell division

细菌细胞分裂的分子机制

• 批准号: RGPIN-2020-04497
• 负责人: Khursigara, Cezar
• 金额: $ 4.23万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=739995
• 关键词: Molecular; mechanisms; bacterial; cell; division

Cell division is one of the most fundamental processes in biology. Bacterial cells divide through the coordinated action of multiple protein systems that replicate genes, expand cellular envelopes, and partition cells to give rise to progeny. The collection of cell division proteins is commonly known as the divisome. In Gram-negative bacteria, the divisome drives the synchronized invagination of the inner- and outer-membranes along with peptidoglycan (PG) synthesis at the newly formed septum. To achieve this, divisome proteins form a multicomponent ring-like structure at the site of cell division. In Escherichia coli, ~10 essential and over 20 nonessential proteins are involved in divisome assembly. The protein interactions occur in a hierarchical manner, starting with the cell division protein FtsZ, a bacterial tubulin homolog. Polymerization of FtsZ at midcell forms a cytoskeletal scaffold known as the Z ring. FtsA and ZipA tether the Z ring to the inner membrane, while a series of FtsZ associated proteins, ZapA to D, subsequently localize at the cell division site independently of each other and likely act to stabilize and organize the Z ring. Next, several integral membrane proteins, FtsK, FtsQ, FtsL/FtsB, FtsW, FtsI, and FtsN, are sequentially recruited to the Z ring. FtsI, FtsW, and FtsN are required for septal PG synthesis, while the FtsQ/FtsL/FtsB heterocomplex and FtsK may connect the Z ring to the proteins involved in PG synthesis. Bacterial cell division has been intensively studied at the cellular and molecular levels for decades and many of the key protein players have been identified. However, critical questions remain about the molecular mechanisms and protein interactions that govern the formation and action of the cell division machinery. The objectives of this research program are built directly on my previous NSERC Discovery Grant. We will use multidisciplinary and complementary approaches to reveal important aspects of protein-protein interactions that drive the formation of the bacterial divisome and the mechanism of bacterial cell division. This research program will give HQP the opportunity to engage in cutting-edge scientific endeavors, with an explicit emphasis on problem solving and collaboration building. Combined with guidance and encouragement, these opportunities will lead to high-impact publications and the development of imaginative, independent scientists who will be well prepared for careers in Canadian academia, government and industry.

细胞分裂是生物学中最基本的过程之一。细菌细胞通过多种蛋白质系统的协调作用分裂，这些蛋白质系统复制基因，扩展细胞信封和分区细胞以产生后代。细胞分裂蛋白的收集通常称为分裂体。在革兰氏阴性细菌中，分裂体在新形成的隔膜上驱动内膜和外膜的同步内部和肽聚糖（PG）合成。为此，在细胞分裂部位形成多组分环形结构。在大肠杆菌中，〜10个必需的和20多种非必要蛋白参与了分裂组装。蛋白质相互作用以分层方式出现，从细胞分裂蛋白FTSZ（一种细菌微管蛋白同源物）开始。 FTSZ在Midcell上的聚合形成了一种被称为Z环的细胞骨架支架。 FTSA和Zipa将Z环链接到内膜，而一系列FTSZ相关的蛋白，Zapa至D，随后将彼此独立于彼此的细胞分裂位点定位，并且可能作用于稳定和组织Z环。接下来，将几种整体膜蛋白（FTSK，FTSQ，FTSL/FTSB，FTSB，FTSW，FTSI和FTSN和FTSN）顺序序列地募集到Z环上。中间PG合成需要FTSI，FTSW和FTSN，而FTSQ/FTSL/FTSL/FTSB Heterocomplex和FTSK可能会将Z环连接到涉及PG合成的蛋白质。 数十年来，已经在细胞和分子水平上对细菌细胞分裂进行了深入研究，并且已经鉴定出许多关键蛋白质参比。但是，关于控制细胞分裂机制的形成和作用的分子机制和蛋白质相互作用的关键问题。该研究计划的目标直接建立在我以前的NSERC Discovery Grant上。我们将使用多学科和互补方法来揭示蛋白质 - 蛋白质相互作用的重要方面，这些方面驱动细菌分裂体的形成和细菌细胞分裂的机制。该研究计划将使HQP有机会从事尖端的科学努力，并明确强调解决问题和协作建设。结合指导和鼓励，这些机会将导致高影响力的出版物以及富有想象力的独立科学家的发展，他们将为加拿大学术界，政府和工业的职业做好充分的准备。