Deciphering the molecular circuitry that controls cell cycle progression in bacteria

维持基因组的完整性对细胞生存至关重要。为了完成这一重要任务， 包括染色体复制、分离和胞质分裂的适当定时在内的细胞周期事件， 在时间和空间上协调一致。任何扰乱这种协调的缺陷都可能是致命的。虽然 复制、分离和细胞分裂在细菌中得到了广泛的研究，我们对它们是如何发生的理解， 这些进程的协调仍然有限。细菌的生存也取决于它们的能力， 协调细胞周期进程与环境波动。在这个项目中，我们专注于保守的 染色体复制起始蛋白DnaA及其非复制功能。长期目标是 表征协调细胞周期进程的调节剂的分子功能， 是潜在的药物靶点该项目的总体目标是确定用于 在时间上协调染色体复制的开始与细胞周期的进展， 细菌模型系统新月柄杆菌。核心假设是DnaA控制着 参与染色体分离和细胞大小决定的关键调节因子。目标1的重点是 定义DnaA如何协调染色体复制与分离的开始，通过表征 在细胞周期中DNA与染色体位点着丝粒的物理关联。的焦点 目的2是确定DnaA活性与细胞大小调节及其依赖性之间的分子网络 关于养分的可利用性。从这个项目中获得的信息将为战略提供有价值的见解 细菌用来在时间和空间上协调多种机制，这些机制是细菌生长的基础。 细胞存活

Maintaining the integrity of the genome is essential to cell survival. To accomplish this vital task, major cell cycle events including chromosome replication, segregation, and proper timing of cytokinesis are exquisitely coordinated, temporally and spatially. Any defect that disturbs this coordination can be lethal. Although replication, segregation, and cell division have been extensively studied in bacteria, our understanding of how these processes are coordinated remains limited. Bacteria’s survival also depends on their ability to coordinate cell cycle progression with environmental fluctuations. In this project, we focus on the conserved chromosome replication initiator protein DnaA and its non-replicative functions. The long-term goal is to characterize the molecular functions of regulators that coordinate the progression of the cell cycle and thus represent potential drug targets. The overall objective of this project is to define the mechanisms used to temporally coordinate the onset of chromosome replication with the progression of the cell cycle using the bacterial model system Caulobacter crescentus. The central hypothesis is that DnaA controls the activity of key regulators involved in chromosome segregation and cell size determination. The focus of Aim 1 is to define how DnaA coordinates chromosome replication with the onset of segregation by characterizing the physical association of DnaA with the chromosomal locus the centromere over the cell cycle. The focus of Aim 2 is to define the molecular network that links DnaA’s activity to cell size regulation and its dependency on nutrient availability. Information garnered from this project will provide valuable insights into strategies used by bacteria to temporally and spatially coordinate the multiple mechanisms that are fundamental for the cell survival.