Characterization of the Bacterial Stress Response Network

细菌利用信号转导途径来感知和适应环境变化。每个途径都包含一个传感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，通过单个信号通路从环境到响应的信息流已经被很好地理解，然而信号通路也由复杂的、不同的连接连接起来，这些连接导致了一个非常敏感的信号网络的形成。尽管人们对这种联系知之甚少，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，一种信号通路可能控制直接影响另一种活性的蛋白质表达。我的研究小组最近发现，大肠杆菌包膜应激反应与其他多种应激反应都有联系。例如，包膜应激导致蛋白质表达的变化，从而影响其他应激反应传感器激酶蛋白的活性。包膜胁迫还改变了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翻译的小rna （sRNAs）的转录水平。有趣的是，包膜胁迫还导致未表征的假定sRNAs和转录因子的表达变化。我假设未表征的包膜胁迫调节的sRNAs和转录因子构成了微生物应激反应网络的一部分，并有助于应激适应。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，并确定对于形成一个非常敏感、集成的大肠杆菌应激反应网络重要的新连接。我们将开始解决我们的长期目标，将我们的分析扩展到大肠杆菌中所有已知的信号通路，以概述控制细胞行为的综合信号网络。

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.