INITITATION OF SPORULATION IN BACILLUS SUBTILIS

枯草芽孢杆菌中孢子形成的引发

• 批准号: 2181136
• 负责人: ALAN D GROSSMAN
• 金额: $ 24.64万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2181136
• 关键词: Bacillus subtilis; DNA damage; DNA replication; bacterial genetics; biological signal transduction; cell differentiation; chromosomes; developmental genetics; gene expression; gene mutation; genetic mapping; genetic regulation; microorganism growth; molecular cloning; nucleic acid sequence; phosphorylation; regulatory gene; site directed mutagenesis; spores; suppressor mutations; transcription factor; transposon /insertion element

Controlled differentiation of cells into specialized cell types depends on the detection of external and internal conditions and transduction of information to the transcription machinery to alter gene expression. In addition, normal growth and development requires the proper replication and segregation of chromosomes, and cells possess regulatory mechanisms that couple division or development to the fidelity of chromosomal transmission, Many diseases, including cancers, result from aberrant regulation of gene expression, and loss of fidelity of chromosome transmission. Microbial pathogenesis depends on the proper control of ene expression in response to changing environments. Our work focuses on the relatively simple developmental process of spore formation in Bacillus subtilis. Basic principles and mechanisms governing development, signal transduction, and gene expression are easily studied in B.subtilis by a combination of physiological, genetic, molecular, and biochemical approaches. Our work with B. subtilis will continue to contribute to a general understanding of mechanisms cells use to control growth, development, and gene expression. The long term goal of our research is to understand the signaling mechanisms that control the initiation of sporulation in B. subtilis. In particular, we are interested in the regulatory pathways controlling gene expression in response to developmental signals. External conditions important for the initiation of sporulation include nutrient deprivation and high cell density. In addition, for cells to begin to sporulate they must be replicating their DNA, have undamaged chromosomes, and have a functioning TCA cycle. All of these conditions control the activity of a multicomponent phospho-transfer pathway (the phosphorelay) that phosphorylates the transcription factor SpoOA. SpoOA-P then activates transcription of several genes needed for sporulation. The phosphorelay functions as a developmental checkpoint to ensure that sporulation begins only when conditions are appropriate. The primary focus of this proposal is to define the mechanisms and signaling pathways that control the phosphorelay in response to DNA replication and DNA damage. In addition, we will continue to dissect regulatory sites and trans-acting factors involved in gene expression early during development We will identify and characterize components of the signaling pathways in B. subtilis that control development in response to DNA replication and DNA damage by isolating mutations that make the initiation of sporulation and activation of SpoOA insensitive to signals related to DNA replication and DNA damage. Characterization of genes on the signaling pathways will provide insights into mechanisms cells use to sense whether their chromosomes are intact and replicated, and how gene expression and development are related accordingly.

细胞受控分化为特化细胞类型取决于 外部和内部条件的检测和转导 向转录机器传递信息以改变基因表达。在 此外，正常的生长和发育需要适当的复制 和染色体分离，细胞具有调节机制 将分裂或发育与染色体的保真度结合起来 传播，许多疾病，包括癌症，都是由异常传播引起的 基因表达的调控和染色体保真度的丧失 传播。微生物发病机制取决于烯的适当控制 表达对环境变化的反应。我们的工作重点是 芽孢杆菌孢子形成的发育过程相对简单 枯草芽孢杆菌。发展、信号的基本原则和机制 枯草芽孢杆菌中的转导和基因表达很容易通过 生理、遗传、分子和生化的结合 接近。我们与枯草芽孢杆菌的合作将继续为 对细胞用于控制生长的机制的一般了解， 发育和基因表达。 我们研究的长期目标是了解信号传导 控制枯草芽孢杆菌中孢子形成起始的机制。在 特别是，我们对控制基因的调控途径感兴趣 表达对发育信号的反应。外部条件 对于孢子形成的启动很重要，包括营养剥夺 和高细胞密度。此外，为了使细胞开始形成孢子，它们 必须能够复制其 DNA，具有未受损的染色体，并且具有 TCA 循环发挥作用。所有这些条件都控制着 多组分磷酸转移途径（磷中继） 磷酸化转录因子 SpoOA。 SpoOA-P 然后激活 孢子形成所需的几个基因的转录。磷光继电器 作为发育检查点，确保孢子形成开始 仅当条件合适时。本提案的主要关注点 是定义控制机制和信号通路 磷酸继电器响应 DNA 复制和 DNA 损伤。此外， 我们将继续剖析监管站点和交易因素 参与发育早期的基因表达 我们将识别和表征信号通路的组成部分 枯草芽孢杆菌 (B. subtilis) 响应 DNA 复制而控制发育， 通过分离导致孢子形成的突变来损伤 DNA SpoOA 的激活对 DNA 复制相关信号不敏感 和DNA损伤。信号通路上基因的表征将 提供对细胞用来感知其是否存在的机制的见解 染色体完整且可复制，以及基因表达和复制如何 发展也相应相关。