Molecular Characterization of Interacting Bacterial Regulatory Networks

相互作用的细菌调节网络的分子表征

• 批准号: 1932780
• 负责人: Lydia Contreras
• 金额: $ 66.3万
• 依托单位: University of Texas at Austin
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1932780&HistoricalAwards=false
• 关键词: Molecular; Characterization; Interacting; Bacterial; Regulatory

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.

细菌具有调节系统网络，可在各种潜在有害的环境中促进生存，例如含有低水平的必需营养物质或高水平的抗细菌剂。 最终，这些调节系统使细菌通过介导与胁迫相关基因的表达来应对破坏性环境，从而使细菌更具耐药性。 该项目的长期目标是更好地了解与压力相关的调节系统如何改变基因表达并促进细菌抗性。 该项目着重于参与后调节的两个RNA结合蛋白，并且是不同全球应力反应系统的一部分。将确定由RNA结合蛋白和应力反应途径共同调节的机制。 该项目将支持对三名大学生的培训以及对两名研究生的跨学科培训。 该项目还将通过现有的“培养未来科学家”计划，并向一个高级生活中心进行公共科学谈判的高级生活中心，以促进对低收入人物不足的社区的广泛推广。对环境中响应环境中“计算”的决策的控制是现代蜂窝和生物分子工程的主要目标之一。尽管环境应力反应的一个重要特征是它们是由动态“ DNA解码网络”介导的，对调节其协调的分子机制的理解是其起步阶段的。例如，全球生物应力响应网络的两个基本问题是：（i）细胞中不同调节剂之间的目标相互作用的独家相互作用如何，以及（ii）目标如何竞争调节剂，尤其是在不同的压力下？此外，考虑到目标与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，退化模式等），特别是在压力期间，如何改变？为了了解这些问题，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，鉴于其监管相互作用，广泛的目标范围，生物学相关性及其机械多样性。 具体而言，研究人员提出：（1）表征双重认可目标的分子调节特征，（2）通过形式上的网络分析建立对双重目标的双重调节功能的影响，结合了传统的RNA蛋白质蛋白生物化学方法和涉及其研究小组的范围和涉及高级概述的特征化的方法和工具，并将其涉及高级统计数据和工具，使用基金会的知识分子优点和更广泛的审查标准，被认为值得通过评估来支持。