GENE EXPRESSION DURING SPORULATION

描述（由申请人提供）：细胞分化是一个基本的生物学过程。其核心是在不同细胞类型中建立不同的基因表达程序，以及基因表达与形态变化的协调。由枯草芽孢杆菌形成孢子是细胞分化的原始系统，由于其易于遗传操作，其已成为研究原核生物中细胞分化的范例。芽孢形成的所有关键调节因子也在所有测序的芽孢杆菌科物种中鉴定，包括病原体炭疽芽孢杆菌和艰难梭菌。孢子形成涉及到一个特征性的分裂成两种不同的细胞类型，母细胞和前孢子。前孢子被母细胞吞噬并发育成成熟的抗性孢子。孢子形成需要四种RNA聚合酶σ因子的作用，前孢子中的σ F，然后是σ G，母细胞中的σ E，然后是σ k。这里的主要目标是了解区室化的基因表达是如何建立和维持的，以及基因表达是如何与形态变化协调的。大多数建议都集中在B上。枯草杆菌。将进行一系列相互关联的研究。有人建议调查为什么sigmaG活性开关从前孢子母细胞spollAdelta突变体。建议使用我们已经开发的两部分区室化测试来识别和表征前孢子特异性表达所需的SF激活的分裂基因和调节因子。有人建议调查为什么某些SF-指导的基因表达不佳时，他们被重新定位在染色体末端附近。建议识别和表征参与sigmaF和sigmaG活性的时间控制的基因。有人建议调查建立区室化孢子八叠球菌的孢子形成司位于中间，相反，其严重不对称的位置为芽孢杆菌属和梭菌属的物种。

DESCRIPTION (provided by applicant): Cell differentiation is a fundamental biological process. Central to it are the establishment of distinct programs of gene expression in the different cell types and the coordination of gene expression with morphological change. Formation of spores by Bacillus subtilis is a primitive system of cell differentiation that has become a paradigm for the study of cell differentiation in prokaryotes because of the ease of its genetic manipulation. All the key regulators of spore formation are also identified in all sequenced species of Bacillaceae, including the pathogens Bacillus anthracis and Clostridium difficile. Sporulation involves a characteristic division into two distinct cell types, the mother cell and the prespore. The prespore is engulfed by the mother cell and develops into the mature, resistant spore. Sporulation requires the action of four RNA polymerase sigma factors, sigmaF and then sigmaG in the prespore and sigmaE and then in sigmak the mother cell. The major objectives here are to understand how compartmentalized gene expression is established and maintained and how gene expression is coordinated with morphological change. Most of the proposal centers on B. subtilis. A series of interconnected lines of research will be pursued. It is proposed to investigate why sigmaG activity switches from the prespore to the mother cell in spollAdelta mutants. It is proposed to identify and characterize division genes and regulators of sF activation that are required for prespore-specific expression using a two-part compartmentalization test we have developed. It is proposed to investigate why certain sF-directed genes are poorly expressed when they are relocated near the chromosome terminus. It is proposed to identify and characterize genes involved in temporal control of sigmaF and sigmaG activity. It is proposed to investigate the establishment of compartmentalization in Sporosarcina ureae where the sporulation division is medially located, in contrast to its grossly asymmetric location for species of Bacillus and Clostridium.