Characterization of the Bacterial Stress Response Network

细菌使用信号转导途径来感知和适应环境变化。每条途径都包含一个感知元件和一个响应元件，这些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是很好理解的，然而信号通路也由复杂的、不同的连接连接起来，从而形成一个极其敏感的信号网络。尽管人们对此知之甚少，但已经确定了两种类型的联系。一条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条信号通路的基因的转录或翻译。此外，一个信号通路可能控制直接影响另一个信号通路活性的蛋白质的表达。我的团队最近发现，大肠杆菌包膜应激反应显示出这两种类型与多种其他应激反应的联系。例如，包膜应激导致蛋白质表达的变化，从而影响其他应激反应感受器蛋白的活性。包膜胁迫还改变了小RNA(SRNAs)的转录水平，sRNAs调节一般应激反应转录因子SS和渗透压调节因子EnvZ和OmpR的翻译。有趣的是，包膜压力还会导致未知的假定sRNA和转录因子表达的变化。我推测，未知的包膜应激调节sRNA和转录因子构成了微生物应激反应网络的一部分，并对应激适应做出了贡献。我们将使用生物信息学、基因组学、遗传学和生化方法来表征这些调控因子，并确定新的联系，这些联系对于形成一个高度敏感的、完整的大肠杆菌应激反应网络非常重要。我们将开始解决我们的长期目标，即将我们的分析扩展到大肠杆菌中所有已知的信号通路，以便勾勒出一个控制细胞行为的全面信号网络。

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.