RNA POLYMERASE AND BACTERIAL DIFFERENTIATION

本项目的目的是了解枯草芽孢杆菌产孢过程中基因转录的调控，以及产孢基因的表达如何指导并与形态发生过程保持一致。孢子形成包括极隔的形成，它将发育中的细胞分为前孢子和母细胞。最初，两个细胞并排躺在一起，但后来前孢子被母细胞吞没。有证据表明，极隔是一个细胞器，密切参与细胞特异性基因转录的建立。差异转录最初是由前孢子中的转录因子sigmaF和母细胞中的转录因子sigmaE的作用所控制的。吞噬后，sigmaF和sigmaE分别被sigmaG和sigmaK取代。将进行实验以了解隔膜形成如何从中间位置切换到极位置。已知有一条通路将sigmaF的激活与极隔联系起来。将进行实验以了解隔膜相关磷酸酶和抗sigma因子的蛋白水解在sigmaF活化中的作用。sigmaE因子来源于前sigmaE，它在通过蛋白水解过程激活之前与隔膜相关。将进行实验以了解隔膜相关蛋白在限制sigmaE进入母细胞中的作用。sigmaK因子来源于pro-sigmaK，其激活受与sigmaG作用耦合的细胞间通路控制。将进行实验，以确定该途径的组成部分如何介导前信号处理，以响应来自前孢子的信号。孢子的形成涉及在sigmaE控制下产生的形态发生蛋白在前孢子周围的组装。将进行实验以了解该蛋白的定位及其在招募外壳蛋白和触发皮层合成中的作用。这些目标解决分化和形态发生的基本问题，这些问题在许多种类的发育系统中是共同的，包括高等生物中正常和异常发育的复杂系统。

The objectives of this project are to understand the control of gene transcription during sporulation in Bacillus subtilis and how the expression of sporulation genes both directs, and is kept in register with, the course of morphogenesis. Sporulation involves the formation of a polar septum, which divides the developing cell into a forespore and a mother cell. Initially, the two cells lie side-by-side but later the forespore is engulfed by the mother cell. Evidence indicates that the polar septum is an organelle that is intimately involved in the establishment of cell-specific gene transcription. Differential transcription is governed initially by the action of transcription factor sigmaF in the forespore and sigmaE in the mother cell. After engulfment, sigmaF and sigmaE are replaced by sigmaG and sigmaK, respectively. Experiments will be carried out to understand how septum formation switches from a medial to a polar position. A pathway is known that links the activation of sigmaF to the polar septum. Experiments will be carried out to understand the roles of a septum-associated phosphatase and the proteolysis of an antisigma factor in the activation of sigmaF. The sigmaE factor is derived from pro-sigmaE, which associates with the septum prior to undergoing activation by proteolytic processing. Experiments will be carried out to understand the role of a septum-associated protein in restricting sigmaE to the mother cell. The sigmaK factor is derived from pro-sigmaK, whose activation is governed by an intercellular pathway that is coupled to the action of sigmaG. Experiments will be carried out to determine how the components of the pathway mediate pro-sigmaK processing in response to a signal from the forespore. Spore formation involves the assembly around the forespore of a morphogenetic protein that is produced under the control of sigmaE. Experiments will be carried out to understand the localization of this protein and its role in recruiting coat proteins and triggering cortex synthesis. These objectives address basic questions of differentiation and morphogenesis that are common to developing systems of many kinds, including complex systems of normal and abnormal development in higher organisms.