Integration of regulatory networks and subcellular architecture to control the Caulobacter cell cycle

整合调控网络和亚细胞结构来控制柄杆菌细胞周期

• 批准号: 9281784
• 负责人: LUCILLE SHAPIRO
• 金额: $ 64.05万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9281784
• 关键词: Antibiotics; Architecture; Bacteria; Caulobacter; Caulobacter crescentus; Cell Cycle; Cell Differentiation process; Cell division; Cells; Chromosome Structures; Communicable Diseases; Complement; Development; Dimensions; Dissection; Epigenetic Process; Gene Expression; Generations; Genetic; Genetic Transcription; Genome; Goals; Growth; Light; Liposomes; Logic; Molecular; Organism; Pathway interactions; Research; Resistance; Signal Pathway; Signal Transduction; Signaling Protein; Solid; Structural Protein; System; Time; Translations; arctic environment; cell type; daughter cell; design; genetic regulatory protein; imaging modality; mutant; novel; optogenetics; programs; public health relevance; reconstitution; segregation; single molecule; spatiotemporal

 DESCRIPTION (provided by applicant): The fundamental basis for the generation of cellular diversity in all organisms is the asymmetric deployment of structural and regulatory proteins to the cell poles prior to cell division and the consequent differential readout of the genome in the two daughter cells. The bacterium Caulobacter crescentus provides an elegant system in which to decipher the complete molecular circuitry that controls the asymmetry that underlies cell differentiation. As Caulobacter moves through its cell cycle, cell differentiation is accompanied by the polar localization of distinct complements of phospho-signaling proteins. The goals of our research program turn on three important questions: 1- How does a polar matrix nanodomain function to dynamically re-wire polar phosphosignaling pathways to drive cell differentiation and asymmetric cell division? We are approaching this question through reconstitution of the polar environment using liposomes and microfabricated solid substrates, three dimensional superresolution imaging modalities and single molecule tracking in living cells, and the creation of optogenetic mutants that enable instantaneous light-induced reconfiguration of the cell pole composition, thereby allowing us to directly observe the consequences of re-wiring a spatially-restricted signaling cascade in a living cell. 2- How do cell-type specific signaling pathways beget cell type-specific gene expression? We are defining the exquisite complexity of the complete genetic circuitry that uses both transcriptional and translation control to drive cell cyce progression culminating in daughter cells of different cell fate. 3- How does chromosome organization, replication and segregation along the long axis of the cell serve as a timer of cell cycle-regulated transcription using epigenetic mechanisms? Our goal is to integrate these spatiotemporal regulatory paradigms to establish the logic that is applicable to the dissection of asymmetry in all living systems.

 描述（由申请人提供）：在所有生物体中产生细胞多样性的基本基础是在细胞分裂之前结构和调节蛋白不对称地部署到细胞极以及随后在两个子细胞中基因组的差异读出。新月柄杆菌提供了一个优雅的系统，可以破译控制细胞分化的不对称性的完整分子电路。当柄杆菌经历其细胞周期时，细胞分化伴随着细胞分化。我们的研究计划的目标是解决三个重要问题：1-极性基质纳米结构域如何发挥作用，动态重新连接极性磷酸信号通路以驱动细胞分化和不对称细胞分裂？正在通过使用脂质体和微加工固体基质重建极地环境、三维超分辨率成像模式和活细胞中的单分子追踪以及光遗传学的创建来解决这个问题突变体能够瞬时光诱导细胞极组成的重新配置，从而使我们能够直接观察在活细胞中重新连接空间限制的信号级联的后果2-细胞类型特异性信号传导途径如何产生细胞类型。 - 特定基因表达？我们正在定义完整遗传电路的复杂性，该电路使用转录和翻译控制来驱动细胞周期进展，最终形成不同细胞命运的子细胞 3- 染色体如何组织、复制和分离。细胞的长轴作为使用表观遗传机制的细胞周期调节转录的计时器？我们的目标是整合这些时空调节范式，以建立适用于所有生命系统中不对称性剖析的逻辑。