Temporal and spatial control of Caulobacter cell cycle

柄杆菌细胞周期的时空控制

• 批准号: 6743747
• 负责人: Christine Jacobs-Wagner
• 金额: $ 27.84万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6743747
• 关键词: Caulobacter; biological signal transduction; cell cycle; cell cycle proteins; cell differentiation; cell growth regulation; cellular polarity; differential display technique; fluorescence microscopy; gene expression; gene mutation; genetic regulatory element; genetic screening; histology; phosphorylation; protein localization; synchronous cell division

DESCRIPTION (provided by applicant): The applicant's goal is to understand how cells can generate asymmetry and coordinate differentiation with cell cycle progression using the simple model bacterium, C. crescentus. In C. crescentus, the predivisional cell is polarized with a stalk at one pole and a single flagellum at the other pole. Every cell cycle includes an asymmetric division that gives rise to two morphologically and physiologically different daughter cells. The system affords access to genetics, biochemistry, genomics and new cytology tools to look at protein dynamics in live cells. A complex phosphorelay of two-component signal transduction proteins is at the heart of differentiation and cell cycle control in this organism. This project has three objectives: The first objective is to sort out the interactions and functions of several of the two-component proteins that participate in cell cycle control and differentiation. To do this, the investigators will use gene expression profiling, phosphorylation assays as well as cell imaging technology. The second objective is based on the recent observations that several components of this regulatory network exhibit a dynamic behavior of spatial localization, alternating between dispersed distribution and discrete accumulation at the cell pole in a cell cycle-dependent manner. To understand how their cell cycle spatial localization relates to regulation and function, the applicants will determine cis-acting sequences and factors that control polar localization of these signaling proteins. The third objective is to identify new cell cycle regulators using a genetic approach. The ultimate goal is to dissect in time and space the signal transduction mechanisms of the two-component regulatory network that controls the C. crescentus differentiation and cell cycle. Components of this essential cell cycle regulatory network are conserved among medically important microorganisms. Insights gained into the cellular organization of prokaryotes and the mechanisms used by them to control temporal and spatial processes will not only close a gap in our understanding of fundamentals of bacterial physiology and regulation, but will also provide a basis for rational design of new antibacterial agents.

描述(由申请人提供)：申请者的目标是了解细胞如何产生不对称，并使用简单的模式细菌新月弯曲霉来协调分化和细胞周期进展。在Crescentus中，分裂前细胞被极化，一极有柄，另一极有单个鞭毛。每个细胞周期都包括不对称分裂，从而产生两个形态和生理上不同的子细胞。该系统提供了遗传学、生物化学、基因组学和新的细胞学工具来观察活细胞中的蛋白质动力学。一种复杂的双组分信号转导蛋白的磷酸继电器是这种生物体分化和细胞周期控制的核心。该项目有三个目标：第一个目标是找出参与细胞周期控制和分化的几种双组分蛋白质的相互作用和功能。为了做到这一点，研究人员将使用基因表达谱、磷酸化分析以及细胞成像技术。第二个目标是基于最近的观察，即这个调控网络的几个组成部分表现出动态的空间定位行为，以细胞周期依赖的方式在细胞极点分散分布和离散积累之间交替。为了了解它们的细胞周期空间定位如何与调节和功能相关，申请者将确定控制这些信号蛋白的极性定位的顺式作用序列和因素。第三个目标是使用遗传方法识别新的细胞周期调节因子。最终目的是在时间和空间上剖析控制月牙藻分化和细胞周期的双组分调控网络的信号转导机制。这个重要的细胞周期调控网络的组成部分在医学上重要的微生物中是保守的。对原核生物的细胞组织及其控制时间和空间过程的机制的深入了解，不仅将填补我们对细菌生理和调控基础的理解空白，而且将为合理设计新的抗菌剂提供基础。