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。细菌细胞通过多个蛋白质系统的协调作用进行分裂，这些蛋白质系统复制基因、扩大细胞包膜和分隔细胞以产生后代。细胞分裂蛋白的集合通常称为分裂体。在革兰氏阴性细菌中，分裂体驱动内膜和外膜同步内陷，并在新形成的隔膜处合成肽聚糖（PG）。为了实现这一目标，分裂体蛋白在细胞分裂部位形成多组分环状结构。在大肠杆菌中，约 10 种必需蛋白和超过 20 种非必需蛋白参与分裂体组装。蛋白质相互作用以分层方式发生，从细胞分裂蛋白 FtsZ（一种细菌微管蛋白同源物）开始。 FtsZ 在细胞中部聚合形成称为 Z 环的细胞骨架支架。 FtsA 和 ZipA 将 Z 环束缚在内膜上，而一系列 FtsZ 相关蛋白（ZapA 至 D）随后彼此独立地定位在细胞分裂位点，并可能起到稳定和组织 Z 环的作用。接下来，几种整合膜蛋白 FtsK、FtsQ、FtsL/FtsB、FtsW、FtsI 和 FtsN 依次被募集至 Z 环。 FtsI、FtsW 和 FtsN 是间隔 PG 合成所必需的，而 FtsQ/FtsL/FtsB 杂合物和 FtsK 可能将 Z 环连接到参与 PG 合成的蛋白质。 几十年来，人们在细胞和分子水平上对细菌细胞分裂进行了深入研究，许多关键的蛋白质参与者已经被识别出来。然而，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仍然存在关键问题。该研究计划的目标直接建立在我之前的 NSERC 发现补助金的基础上。我们将使用多学科和互补的方法来揭示蛋白质-蛋白质相互作用的重要方面，这些相互作用驱动细菌分裂体的形成和细菌细胞分裂的机制。该研究计划将为总部提供参与尖端科学工作的机会，并明确强调解决问题和建立合作。结合指导和鼓励，这些机会将带来高影响力的出版物和培养富有想象力的独立科学家，他们将为加拿大学术界、政府和工业界的职业生涯做好充分准备。