Characterization of the Bacterial Stress Response Network

细菌通过信号转导途径感知和适应环境变化。每一个通路都包含一个感应元件和一个反应元件，导致适应性基因表达的变化。在许多情况下，信息通过个体信号通路从环境到反应的流动已经得到了很好的理解，然而信号通路也通过复杂、多样化的连接连接来连接，从而导致极其敏感的信号网络的形成。虽然人们对这一点了解甚少，但已经确定了两种类型的联系。一个给定的信号通路可能与细胞中的其他信号通路相连，因为它调节编码另一个信号通路的基因的转录或翻译。此外，一个信号通路可以控制直接影响另一个信号通路活性的蛋白质的表达。我的小组最近表明，大肠杆菌的包膜应激反应证明了这两种类型与多种其他应激反应的联系。例如，包膜应激导致影响其他应激响应传感器激酶蛋白的活性的蛋白质表达的变化。包膜应激还改变调节一般应激反应转录因子sS和渗透压应激调节因子EnvZ和OmpR的翻译的小RNA（sRNA）的转录水平。有趣的是，包膜应激也导致未表征的假定sRNA和转录因子表达的变化。我假设，未表征的包膜压力调节的sRNAs和转录因子的微生物应激反应网络的一部分，并有助于压力适应。我们将使用生物信息学、基因组学、遗传学和生物化学方法来表征这些调节因子，并确定对形成一个非常敏感的、整合的、E.大肠杆菌应激反应网络。我们将开始致力于将我们的分析扩展到E.大肠杆菌，以勾勒出一个全面的信号网络控制细胞的行为。

Bacteria use signal transduction pathways to sense and adapt to environmental changes. Each pathway contains a sensing element and a response element that leads to changes in adaptive gene expression. The flow of information through an individual signaling pathway from the environment through to a response is well understood in many cases, however signaling pathways are also linked by complex, diverse connections that lead to the formation of an exquisitely sensitive signaling network. Although poorly understood, two types of connection have been identified. A given signaling pathway may be linked to others in the cell because it regulates the transcription or translation of genes that encode another signaling pathway. Additionally, one signaling pathway may control the expression of proteins that directly impact the activities of another. My group recently showed that the Escherichia coli envelope stress response demonstrates connections of both types, to multiple other stress responses. For example, envelope stress leads to changes in the expression of proteins that impact the activities of other stress responsive sensor kinase proteins. Envelope stress also changes the transcription levels of small RNAs (sRNAs) that regulate the translation of the general stress response transcription factor sS and the osmolarity stress regulators EnvZ and OmpR. Intriguingly, envelope stress also leads to changes in expression of uncharacterized putative sRNAs and transcription factors. I hypothesize that uncharacterized envelope stress regulated sRNAs and transcription factors form part of the microbial stress response network and contribute to stress adaptation. We will use bioinformatic, genomic, genetic, and biochemical approaches to characterize these regulators and identify new connections important for the formation of an exquisitely sensitive, integrated, E. coli stress response network. We will begin to address our long-term goal of extending our analyses to all known signaling pathways in E. coli in order to outline a comprehensive signaling network controlling cellular behavior.