INITITATION OF SPORULATION IN BACILLUS SUBTILIS

细胞向特化细胞类型的受控分化取决于 内外部条件的检测和转导 信息传递给转录机器以改变基因表达。在……里面 此外，正常的生长和发育需要适当的复制 和染色体的分离，细胞具有调节机制 这对夫妇分裂或发育到染色体的保真度 除了传播，包括癌症在内的许多疾病都是由异常引起的 基因表达调控与染色体失真度 变速箱。微生物致病依赖于烯的适当控制 表达对不断变化的环境的反应。我们的工作重点是 芽孢杆菌芽胞形成相对简单的发育过程 枯草杆菌。管理发展的基本原则和机制，信号 在枯草杆菌中很容易研究转导和基因表达。 生理、遗传、分子和生化的结合 接近了。我们与枯草杆菌的合作将继续为 对细胞用来控制生长的机制有一般的了解， 发育和基因表达。 我们研究的长期目标是理解信号 控制枯草杆菌产孢量启动的机制。在……里面 特别是，我们对控制基因的调控途径感兴趣。 对发育信号做出反应的表达。外部条件 营养物质缺乏对产孢量的启动很重要 和高细胞密度。此外，为了让细胞开始产生孢子，它们 必须复制他们的DNA，有未受损的染色体，并有一个 正常运行的三氯乙酸循环。所有这些条件都控制着 多组分磷酸转移途径(磷酸继电器) 使转录因子SpoOA磷酸化。然后，SpoOA-P激活 孢子形成所需的几个基因的转录。磷光继电器 起到发育检查点的作用，以确保产孢量开始 只有在条件合适的情况下。这项提案的主要重点是 就是定义控制这些信号的机制和信号通路 响应DNA复制和DNA损伤的磷光传递。此外, 我们将继续剖析调控部位和反式作用因素 参与发育早期的基因表达 我们将在以下内容中识别和描述信号通路的组件 枯草杆菌控制发育以响应DNA复制和 分离引起产孢子的突变对DNA的损伤 以及对DNA复制相关信号不敏感的SpoOA的激活 和DNA损伤。信号通路上的基因特征将 提供对细胞用来检测其是否具有 染色体是完整的和复制的，以及基因表达和 发展是相应地相关的。

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.