Global control of differentiation in Caulobacter

发展计划的正确执行需要各个事件以有序的方式进行。分化细胞必须整合DNA复制、细胞分裂和形态变化等过程。该项目的长期目标是了解细胞分裂和细胞分化如何在细菌Caulobacter crescentus中调节和整合。每一次细胞分裂都是不对称的，产生两种不同的细胞类型：一种是游动的游动细胞，另一种是无柄的柄细胞。只有有柄细胞才有能力复制DNA和分裂。不对称的分裂前细胞在一极有鞭毛，在另一极有柄。细胞分裂前不对称性的建立通过DNA复制和细胞分裂检查点与细胞周期进程紧密耦合。拟议的研究有三个主要目标。第一个目标是确定负责细胞分裂的细胞周期控制的机制。将细胞分裂与DNA复制偶联的一个检查点由主细胞周期反应调节因子CtrA介导。提出实验来确定CtrA的活性如何受DNA复制的调节，以及细胞如何通过在每个细胞周期结束时降解细胞分裂蛋白来设置复制检查点的阶段。第二个目标是确定基因和细胞分裂检查点机制，耦合极性发展细胞分裂。细胞分裂检查点需要σ-54特异性反应调节剂TacA，并将确定其作用机制。将鉴定和研究参与检查点控制的TacA依赖性基因，并确定将细胞分裂抑制转导至TacA的机制。第三个目标是研究极性细胞器发育蛋白PodJ在调节皮利和固着物合成中的功能，这两个事件被细胞分裂检查点阻断。将确定PodJ在发展的关键调节剂的本地化的作用和PodJ蛋白水解加工，这是耦合到细胞分裂的机制，将进行调查。这些研究将导致更好地理解调节细胞分化的机制。

The correct execution of a developmental program requires that individual events proceed in an orderly fashion. Differentiating cells have to integrate processes such as DNA replication, cell division, and changes in morphology. The long-term goal of this project is to understand how cell division and cell differentiation are regulated and integrated in the bacterium Caulobacter crescentus. Each cell division is asymmetric and produces two different cell types: a motile swarmer cell and a sessile stalked cell. Only the stalked cell is competent to replicate DNA and divide. The asymmetric predivisional cell has a flagellum at one pole and a stalk at the opposite pole. The establishment of asymmetry prior to cell division is tightly coupled to cell cycle progression by DNA replication and cell division checkpoints. The proposed research has three main objectives. The first objective is to identify the mechanisms responsible for the cell cycle control of cell division. One checkpoint that couples cell division to DNA replication is mediated by the master cell cycle response regulator CtrA. Experiments are proposed to determine how the activity of CtrA is regulated by DNA replication and how the cell sets the stage for the replication checkpoint by degrading cell division proteins at the end of every cell cycle. The second objective is to define the genes and the cell division checkpoint mechanism that couple polar development to cell division. The sigma-54 specific response regulator, TacA, is required for the cell division checkpoint and its mechanism of action will be determined. The TacA-dependent gene(s) involved in checkpoint control will be identified and studied, and the mechanism by which cell division inhibition is transduced to TacA will be determined. The third objective is to investigate the function of the polar organelle development protein, PodJ, in regulating pili and holdfast synthesis, two events that are blocked by the cell division checkpoint. The role of PodJ in the localization of critical regulators of development will be determined and the mechanism of PodJ proteolytic processing, which is coupled to cell division, will be investigated. These studies will lead to a better understanding of the mechanisms that regulate cell differentiation.