Mutational Analysis of E. Coli Core RNA Polymerase

我们的基本兴趣是细胞如何调节信息传递的中心生物学问题， 基因到蛋白质。我们的目标是了解决策过程的基础转录 RNA聚合酶（RNAP）。在原核生物体中，细胞中的sigma谱 转录启动并构成决策过程的主要输入。我们将探索 sigma输入和RNAP输出之间的关系，从分子到基因组的水平。 在目前的资助期内，我们将： 1.严格定义西格玛在熔融促进剂DMA中的作用。 2.定义sigma组的共同和独特的功能方面。 3.评估RNA聚合酶状态的细胞读数。 4.研究在远亲基因组中交替sigma's及其调节子的进化。 这些研究确定了sigma对转录的基本贡献， 在sigma亚家族之间，开发预测启动子的方法，并了解如何 全酶状态的改变被转化为细胞调节回路。这样的信息可以 用于设计专门针对细菌过程的新药。考虑到细菌的保守性 全酶，我们的结果将通知所有细菌的研究，包括病原体和bidterrorism危害。 此外，我们正在提出的问题和我们正在开发的方法将使我们能够使用大量的 基因组信息现在可以用来了解其他细菌，这些细菌可能很难甚至不可能被 实验研究。

Our fundamental interest is the central biological problem of how a cell regulates transfer of information from genes to proteins. Our goal is to understand the decision making process that underlies the transcriptional output of RNA polymerase (RNAP). In prokaryotic organisms, the cellular repertoire of sigmas orchestrate transcription initiation and constitute a major input to the decision-making process. We will probe the relationship between sigma input and RNAP output at levels ranging from the molecular to the genomic. During the current granting period, we will: 1. Critically define the role of sigma in melting promoterDMA. 2. Define common and unique functional aspects of sigma groups. 3. Assess cellular readout of RNA polymerase status. 4. Investigate the evolution of alternative sigma's and their regulons in distantly related genomes. These studies determine the fundamental contributions of sigma's to transcription, identify differences between the sigma subfamilies, develop the methodology to predict promoters and to understand how altering the status of holoenzyme is translated into cellular regulatory circuits. Such information could be used to design new drugs that specifically target bacterial processes. Given the conservation of bacterial holoenzyme, our results will inform studies of all bacteria, including pathogens and bidterrorism hazards. Moreover, the questions we are asking and the methods we are developing will allow us to use the vast genomic information now available to understand other bacteria that may be difficult or even impossible to study experimentally.