Bacterial Differentiation

描述(申请人提供)：枯草芽孢杆菌从繁殖体到休眠内孢子的分化为发育生物学基本问题的研究提供了一个强有力的模型。总体目标是了解分化过程中基因表达与细胞结构组装是如何协调的。在孢子形成开始时，一个磷酸传递系统控制早期基因表达的时间。随着分化的继续，基因表达与特定形态标志的完成相联系，并在两个细胞之间同步。此外，形态发生蛋白引导并可能调节亚细胞结构的构建。在本应用程序中，我们将研究在这些发展阶段的每个阶段运行的调节机制。在第一个目标中，我们将研究两个反应调节子(Spo0A和Phop)如何相互作用，以产生克隆群体的两个表型不同的部分。在第二个目标中，我们研究了新发现的连接两个细胞(前孢子和母细胞)的通道在内孢子发育过程中的作用，在第三个目标中，我们研究了两个转录因子在细胞类型特异性限制RNA聚合酶西格玛因子活性中的潜在作用。在最后的目的中，我们研究了GTP/ATP水解蛋白在内孢子复杂外壳蛋白结构组装中的作用。这些目标中的任何一个的成功都将代表着大量的新信息，并对我们在细胞生物学和细胞间通信的广泛领域的想法产生重大影响。公共卫生相关性：枯草芽孢杆菌与人类重要的病原体细菌有关。然而，枯草杆菌更易于分析。因此，这项研究的结果将更容易为控制这些相关病原菌的生长、生存和其他生物学活动的分子机制提供见解。

DESCRIPTION (provided by applicant): Differentiation of the bacterium Bacillus subtilis from the vegetative form into a dormant endospore has provided a powerful model for the study of fundamental problems in developmental biology. The overall goal is to understand how gene expression is coordinated with the assembly of cellular structures during differentiation. At the onset of sporulation a phosphorelay system controls the timing of early gene expression. As differentiation continues gene expression is coupled to the completion of specific morphological landmarks, and is synchronized between two cells. Additionally, morphogenetic proteins guide, and possibly regulate, the construction of sub-cellular structures. In this application we will investigate regulatory mechanisms that operate at each of these stages of development. In the first aim we will examine how two response regulators (Spo0A and PhoP) interact to produce two phenotypically different fractions of a clonal population. In the second aim we examine the role of newly discovered channel that connects two cells (forespore and mother cell) during endospore development, and in the third aim investigate the potential roles of two transcription factors in cell-type specific restriction of RNA polymerase sigma factor activity. In the final aim we examine the role of a GTP/ATP hydrolyzing protein in the assembly of the complex coat protein structure of endospores. Success in any one of these aims would represent substantial new information, and significantly impact our ideas in broad areas of cell biology and intercellular communication. PUBLIC HEALTH RELEVANCE: The bacterium Bacillus subtilis, is related to bacteria that are important human pathogens. However, B. subtilis is more amenable to analysis. Therefore, the results of this research will more readily provide insights into the molecular mechanisms governing the growth, survival, and other biological activities of these related pathogenic bacteria.