INITITATION OF SPORULATION IN BACILLUS SUBTILIS

细胞向特化细胞类型的受控分化取决于 外部和内部条件的检测以及 将信息传递给转录机器以改变基因表达。在 此外，正常的生长和发育需要适当的复制， 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 许多疾病，包括癌症，都是由异常的 基因表达的调控和染色体保真度的丧失 传输微生物致病依赖于适当控制烯 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一个相对简单的发育过程 枯草芽孢杆菌发展的基本原则和机制， 转导和基因表达在B.subtilis中很容易通过 生理学、遗传学、分子学和生物化学的结合 接近。我们和B的合作。枯草将继续作出贡献， 对细胞控制生长机制的一般理解， 发育和基因表达。 我们研究的长期目标是了解 控制B中孢子形成起始的机制。枯草芽孢杆菌在 特别是，我们感兴趣的调控途径控制基因 对发育信号的反应。外部条件 对孢子形成起始很重要的包括营养缺乏 和高细胞密度。此外，细胞开始形成孢子， 必须复制他们的DNA，有未受损的染色体，并有一个 运行TCA循环。所有这些条件都控制着 多组分磷酸转移途径（磷酸转移）， 磷酸化转录因子SpoOA。SpoOA-P随后激活 孢子形成所需的几个基因的转录。磷继电器 作为一个发育检查点，以确保孢子形成开始 只有在条件合适的时候。该提案的主要重点是 是为了确定控制这些疾病的机制和信号通路， 磷酸化介导对DNA复制和DNA损伤的反应。此外，本发明还提供了一种方法， 我们将继续研究调控位点和反式作用因子， 在发育早期参与基因表达 我们将识别和表征的信号通路的组成部分， B。枯草芽孢杆菌，其控制响应DNA复制的发育， 通过分离导致孢子形成起始的突变而造成的DNA损伤 SpoOA对DNA复制相关信号不敏感 和DNA损伤对信号通路基因的表征将 深入了解细胞用来感知它们是否 染色体是完整和复制的，基因表达和 发展是相应的。

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.