Molecular mechanisms of bacterial cell division

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、扩展细胞包膜并划分细胞以产生后代。细胞分裂蛋白的集合通常被称为分裂体。在革兰氏阴性菌中，分裂体驱动内外膜的同步内陷，沿着新形成的隔膜处的肽聚糖（PG）合成。为了实现这一点，分裂体蛋白在细胞分裂位点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级方式发生，从细胞分裂蛋白FtsZ（细菌微管蛋白同源物）开始。FtsZ在中间细胞处的聚合形成称为Z环的细胞骨架支架。FtsA和ZipA将Z环拴在内膜上，而一系列FtsZ相关蛋白，ZapA到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，几个完整的膜蛋白，FtsK，FtsQ，FtsL/FtsB，FtsW，FtsI和FtsN，依次募集到Z环。FtsI、FtsW和FtsN是隔PG合成所需的，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，并且已经确定了许多关键蛋白质参与者。然而，关键的问题仍然是关于分子机制和蛋白质相互作用，支配细胞分裂机制的形成和行动。这项研究计划的目标是直接建立在我以前的NSERC发现补助金。我们将使用多学科和互补的方法来揭示驱动细菌分裂体形成和细菌细胞分裂机制的蛋白质-蛋白质相互作用的重要方面。该研究计划将使HQP有机会从事尖端科学工作，明确强调解决问题和建立合作。结合指导和鼓励，这些机会将导致高影响力的出版物和富有想象力的独立科学家的发展，他们将为加拿大学术界，政府和工业界的职业生涯做好准备。

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.