Bacterial Differentiation

描述（由申请人提供）：枯草芽孢杆菌从营养形态分化为休眠的内孢子，为研究发育生物学的基本问题提供了一个强有力的模型。总体目标是了解在分化过程中基因表达是如何与细胞结构组装协调的。在产孢开始时，一个磷接力系统控制着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耦合，并在两个细胞之间同步。此外，形态发生蛋白指导并可能调节亚细胞结构的构建。在本应用程序中，我们将研究在每个开发阶段运行的监管机制。在第一个目标中，我们将研究两个反应调节因子（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，我们研究了在孢子内发育过程中连接两个细胞（前孢子和母细胞）的新发现的通道的作用，在第三个目标中，我们研究了两种转录因子在细胞类型特异性限制RNA聚合酶sigma因子活性中的潜在作用。在最后的目的中，我们研究了GTP/ATP水解蛋白在孢子内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大量的新信息，并显著影响我们在细胞生物学和细胞间通讯的广泛领域的想法。公共卫生相关性：枯草芽孢杆菌是一种重要的人类病原体。然而，枯草芽孢杆菌更易于分析。因此，这项研究的结果将更容易地为这些相关致病菌的生长、生存和其他生物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.