Global control of differentiation in Caulobacter

发展计划的正确执行需要个别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。这个项目的长期目标是了解细胞分裂和细胞分化是如何在新月弯杆菌中调节和整合的。每一次细胞分裂都是不对称的，产生两种不同的细胞类型：活动的丛生细胞和无柄的柄细胞。只有有柄的细胞才有能力复制DNA并分裂。不对称的分裂前细胞一极有鞭毛，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相连。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复制结合起来的一个检查点是由主细胞周期反应调节因子CtrA介导的。我们提出了一些实验，以确定CtrA的活性是如何受到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为复制检查点奠定基础。第二个目标是定义将极地发育与细胞分裂联系起来的基因和细胞分裂检查点机制。细胞分裂检查点需要Sigma-54特异性反应调节因子TACA，其作用机制将被确定。将对参与检查点控制的TACA依赖基因(S)进行鉴定和研究，并将确定细胞分裂抑制转导到TACA的机制。第三个目标是研究极细胞器发育蛋白PodJ在调节菌毛和Holdfast合成方面的功能，这两个事件被细胞分裂检查点阻止。将确定PodJ在定位发育关键调控因子中的作用，并将研究与细胞分裂相耦合的PodJ蛋白分解处理的机制。这些研究将有助于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.