Global control of differentiation in Caulobacter

一个发展计划的正确执行要求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月牙根杆菌中细胞分裂和细胞分化是如何被调节和整合的。每一个细胞分裂都是不对称的，产生两种不同的细胞类型：运动的蜂群细胞和无梗的蜂群细胞。只有被跟踪的细胞才有能力复制DNA并分裂。不对称的未分裂细胞的一端有鞭毛，另一端有茎。通过DNA复制和细胞分裂检查点，细胞分裂前不对称性的建立与细胞周期进程紧密相关。拟议的研究有三个主要目标。第一个目标是确定负责细胞周期控制细胞分裂的机制。一个将细胞分裂与DNA复制结合的检查点是由主细胞周期反应调节因子CtrA介导的。研究人员建议通过实验来确定DNA复制如何调节CtrA的活性，以及细胞如何在每个细胞周期结束时通过降解细胞分裂蛋白为复制检查点设置阶段。第二个目标是定义将极性发育与细胞分裂偶联的基因和细胞分裂检查点机制。sigma-54特异性反应调节因子TacA是细胞分裂检查点所必需的，其作用机制将被确定。将鉴定和研究参与检查点控制的TacA依赖基因，并确定细胞分裂抑制转导到TacA的机制。第三个目的是研究极性细胞器发育蛋白PodJ在调节毛和固定物合成中的功能，这两个事件被细胞分裂检查点阻断。将确定PodJ在发育关键调控因子定位中的作用，并研究与细胞分裂耦合的PodJ蛋白水解加工的机制。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.