Global control of differentiation in Caulobacter

发展计划的正确执行需要各个事件有序地进行 时尚.分化细胞必须整合DNA复制、细胞分裂和变化等过程 在形态学上。这个项目的长期目标是了解细胞分裂和细胞分化 在新月柄杆菌中被调节和整合。每个细胞分裂都是不对称的， 产生两种不同的细胞类型：能动的蜂群细胞和无柄的柄细胞。只有被跟踪的细胞 能够复制DNA并分裂。不对称的分裂前细胞在一端有鞭毛， 在另一个极点上潜行。细胞分裂前不对称性的建立与细胞分裂紧密相关， 通过DNA复制和细胞分裂检查点进行细胞周期进展。研究主要有三个方面。 目标.第一个目标是确定负责细胞周期控制的机制， 师.一个将细胞分裂与DNA复制结合起来的检查点是由主细胞周期介导的 响应调节器CtrA。提出实验来确定CtrA的活性如何被调节， DNA复制以及细胞如何通过降低细胞分裂为复制检查点设置阶段 在每个细胞周期结束时的蛋白质。第二个目标是确定基因和细胞分裂 将极性发育与细胞分裂结合起来的检查点机制。sigma-54特异性反应 调节剂TacA是细胞分裂检查点所必需的，其作用机制将被确定。 将鉴定和研究涉及检查点控制的TacA依赖性基因， 将确定细胞分裂抑制被转导至TacA的机制。第三个目标是 探讨极性细胞器发育蛋白PodJ在调节皮利和粘附中的作用 合成，两个被细胞分裂检查点阻断的事件。PodJ在本地化中的作用 将确定发育的关键调节剂和PodJ蛋白水解加工的机制， 与细胞分裂相关的基因。这些研究将有助于更好地了解 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.