Molecular Characterization of Interacting Bacterial Regulatory Networks

细菌具有调节系统网络，以促进在各种潜在有害环境中生存，例如含有低水平必需营养素或高水平抗菌剂的环境。 最终，这些调节系统使细菌能够通过介导应激相关基因的表达来应对破坏性环境，从而使细菌更具抵抗力。 该项目的长期目标是更好地了解压力相关的调节系统如何改变基因表达并促进细菌耐药性。 该项目重点关注两种RNA结合蛋白，它们参与转录后调节，并且是不同全球应激反应系统的一部分； RNA结合蛋白和应激反应途径的共同调节机制将被确定。 该项目将支持三名本科生的培养和两名研究生的跨学科培养。 该项目还将通过现有的“培养未来科学家”计划，促进更广泛的接触低收入群体，并在老年生活中心举办公共科学讲座。控制细胞中根据环境“计算”的决策是现代细胞和生物分子工程的主要目标之一。尽管环境应激反应的一个重要特征是它们是由动态“DNA解码网络”介导的，但对调节其协调的分子机制的理解还处于起步阶段。例如，全球生物应激反应网络的两个基本问题是：（i）细胞中不同调节因子之间的靶标相互作用有多排他性；（ii）靶标如何竞争调节因子，特别是在不同的压力下？此外，思考一下是否很有趣：目标和竞争监管机构之间的不同相互作用如何改变目标的命运（即稳定性、降解模式等），特别是在压力期间？为了深入了解这些问题，研究人员建议使用大肠杆菌碳储存（Csr）和 Hfq 网络作为模型系统，因为它们的监管相互作用、广泛的目标范围、生物相关性及其机制多样性。 具体来说，研究人员建议：（1）表征双重识别靶点的分子调控特征，以及（2）结合传统的RNA-蛋白质生物化学方法以及其研究小组开发的涉及高通量组学表征的最新方法和工具，通过正式网络分析确定双重靶点调控的双重调控功能的影响。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

Bacteria have networks of regulatory systems to facilitate survival in a variety of potentially harmful environments such as those containing low levels of essential nutrients or high levels of anti-bacterial agents. Ultimately, these regulatory systems allow bacteria to cope with damaging environments by mediating expression of stress-associated genes, which in turn make the bacteria more resistant. The long-term goal of this project is to better understand how stress-associated regulatory systems alter gene expression and promote bacterial resistance. This project focuses on two RNA binding proteins that are involved in post-transcriptional regulation and are part of different global stress response systems; the mechanisms of co-regulation by the RNA binding proteins and stress response pathways will be determined. This project will support the training of three undergraduates and the interdisciplinary training of two graduate students. This project will also facilitate broader outreach to a low-income underrepresented community through the existing "Raising Future Scientists" program and to a senior living center where public science talks will be given.Control of the decisions that are "computed" in cells in response to the environment is one of the main objectives of modern cellular and biomolecular engineering. Although an important feature of environmental stress responses is that they are mediated by dynamic "DNA decoding networks," understanding of the molecular mechanisms that regulate their coordination is in its infancy. For instance, two fundamental questions of global biological stress-response networks are: (i) how exclusive are target interactions amongst different regulators in the cell and, (ii) how do targets compete for regulators, particularly under different stresses? Moreover, is it is intriguing to think about: how could different interactions between a target and competing regulators change the fate (i.e. stability, degradation patterns etc.) of the target, particularly during stress? To get insight into these questions, the researchers propose to use the E. coli carbon storage (Csr) and the Hfq networks as model systems given their regulatory interactions, broad target scope, biological relevance and their mechanistic diversity. Specifically, the researchers propose to: (1) Characterize molecular regulatory features of dually recognized targets, and to (2) Establish the impact of dual regulatory function of the regulation of the dual targets via formal network analysis using a combination of traditional RNA-protein biochemistry methods as well as recent methods and tools developed by their research group involving high-throughput omics characterizations.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.