Quorum sensing and gene expression in Bacillus subtilis

描述（申请人提供）：细胞-细胞信号传导控制着生物世界的许多过程，包括发育、发病、生长、交配和转化。信号传导过程通常由一些细胞产生并被其他细胞感知的因子（如激素、信息素、神经递质）介导。在细菌中，感知和响应高种群密度的能力是一种细胞信号，通常被称为群体感应。细胞产生细胞外信号分子，随着种群密度的增加而积累，在临界密度时发生生理反应。该项目的长期目标是了解枯草芽孢杆菌如何调节基因表达和发育以响应环境条件，特别关注肽和细胞-细胞信号传导方面。枯草芽孢杆菌群体感应的主要途径涉及转录因子ComA的激活，这是一种在磷酸化时激活的反应调节因子。至少有两种不同的肽信号分子在细胞生长到高人口密度时积聚在培养上清中，从而调节ComA的活性。一个主要的挑战是阐明单个物种中由细胞-细胞信号控制的细胞过程的范围。这包括描述受种群密度调节的基因，识别信号分子和途径，以及描述种群密度反应和其他生理信号之间重叠相互作用的网络。我们将通过描述依赖于昏迷的群体反应，描述可能参与细胞-细胞信号传导的其他基因，以及直接测试和描述其他细胞密度调节反应来研究这些问题。该项目的核心是使用DNA微阵列来表征各种条件下和各种突变体的mRNA水平。我们对枯草芽孢杆菌群体感应和基因表达的研究是相对简单的，实验可获得的微生物应该为细胞-细胞信号传导，信号转导和调控的一般机制提供见解。

DESCRIPTION (provided by applicant): Cell-cell signaling controls many processes in the biological world, including development, pathogenesis, growth, mating, and transformation. Signaling processes are often mediated by factors (e.g. hormones, pheromones, neurotransmitters) that are produced by some cells and sensed by others. In bacteria, the ability to sense and respond to high population density is a type of cell-cell signaling often referred to as quorum-sensing. Cells produce extracellular signaling molecules that accumulate as population density increases, and a physiological response occurs at a critical density. The long-term goal of this project is to understand how Bacillus subtilis modulates gene expression and development in response to environmental conditions, with particular focus on aspects of peptide and cell-cell signaling. The major pathway for quorum sensing in B. subtilis involves activation of the transcription factor ComA, a response regulator that is active when phosphorylated. The activity of ComA is modulated by at least two different peptide signaling molecules that accumulate in culture supernatant as cells grow to high population density. A major challenge is to elucidate the range of cellular processes that are controlled by cell-cell signaling in a single species. This includes characterizing the genes that are regulated in response to population density, identifying the signaling molecules and pathways, and characterizing the web of overlapping interactions between responses to population density and other physiological signals. We will investigate these issues by characterizing the ComA-dependent quorum response, by characterizing other genes that are likely to be involved in cell-cell signaling, and by testing directly for and characterizing additional cell density-regulated responses. Central to this project is the use of DNA microarrays to characterize mRNA levels under a variety of conditions and in a variety of mutants. Our studies on quorum sensing and gene expression in B. subtilis, are relatively simple, experimentally accessible microbe should provide insights into general mechanisms of cell-cell signaling, signal transduction, and regulation.