Quorum sensing and gene expression in Bacillus subtilis

描述（由申请人提供）：细胞-细胞信号传导控制生物世界中的许多过程，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（例如激素、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-细胞信号传导，通常被称为群体感应。细胞产生细胞外信号分子，随着人口密度的增加而积累，并且在临界密度下发生生理反应。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应对环境条件，特别关注肽和细胞-细胞信号传导方面。B中群体感应的主要途径。枯草芽孢杆菌的活化涉及转录因子ComA的活化，ComA是一种在磷酸化时有活性的反应调节因子。ComA的活性由至少两种不同的肽信号分子调节，所述肽信号分子随着细胞生长到高群体密度而在培养上清液中积累。一个主要的挑战是阐明在一个单一的物种中由细胞-细胞信号控制的细胞过程的范围。这包括表征响应于人口密度而调节的基因，识别信号传导分子和途径，以及表征对人口密度和其他生理信号的响应之间的重叠相互作用的网络。我们将通过表征ComA依赖的群体响应，通过表征可能参与细胞-细胞信号传导的其他基因，以及通过直接测试和表征额外的细胞密度调节响应来研究这些问题。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中的mRNA水平。我们对B中群体感应和基因表达的研究。枯草芽孢杆菌是相对简单的、实验上可获得的微生物，应该提供对细胞-细胞信号传导、信号转导和调节的一般机制的见解。

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.