Bacterial Differentiation

描述（由申请人提供）：枯草芽孢杆菌从营养体分化为休眠内生孢子，为发育生物学基本问题的研究提供了一个强有力的模型。总体目标是了解基因表达如何与分化过程中细胞结构的组装协调。在孢子形成开始时，磷酸化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关联，并且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。在本申请中，我们将研究在这些发展阶段中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器（Spo 0A和PhoP）如何相互作用，产生两个表型不同的克隆种群的分数。在第二个目标中，我们研究了新发现的通道，连接两个细胞（前孢子和母细胞）在内生孢子发育过程中的作用，并在第三个目标调查的潜在作用的两个转录因子的RNA聚合酶σ因子活性的细胞类型特异性限制。在最后的目标，我们研究的GTP/ATP水解蛋白的作用，在组装的复杂的外壳蛋白结构的内生孢子。其中任何一个目标的成功都将代表大量新信息，并对我们在细胞生物学和细胞间通讯等广泛领域的想法产生重大影响。 公共卫生相关性：枯草芽孢杆菌与重要的人类病原体细菌有关。然而，B。枯草芽孢杆菌更易于分析。因此，这项研究的结果将更容易提供有关这些相关病原菌的生长，存活和其他生物活性的分子机制的见解。

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.