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Collaborative Research: A Model for Divergent Bacterial Signaling Networks; Linking New Cyclic Dinucleotides to Environmental and Electrical Lifestyles

合作研究：不同细菌信号网络的模型；

基本信息

批准号：
1716256
负责人：
Ming Hammond
金额：
$ 42万
依托单位：
University of California-Berkeley
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2019-03-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1716256&HistoricalAwards=false
关键词：
Collaborative Research Model Divergent Bacterial

项目摘要

Some environmental bacteria have the ability to detect, attach to and react with metal particles. This process causes release of essential minerals into rivers and lakes, and reduces toxicity of heavy metal contaminants in waste sites undergoing bioremediation. This collaborative project focuses on the recent discovery of a mechanism that enables bacteria to sense and respond to these important metals. As these bacteria are also capable of attaching to electrodes, new techniques for monitoring metal decontamination could harness these sensing systems. The researchers will use molecular techniques to look inside the bacteria, where they will determine how sensing of these metals switches genes and proteins on and off in response to different types of metal surfaces. This project will provide cross-disciplinary college-level training including experiential biology modules in Minnesota and internship programs serving community college and undergraduate students in California. As outreach to K-12 students, we will adapt hands-on educational demonstrations that exhibit the link between chemistry, water quality, and this unique microbial-electrical activity. Finally, we will expand YouSTEM.org, a website created by the Hammond lab for the general public to find information about free K-12 STEM programs, to add the Minneapolis/St. Paul area.Cyclic di-GMP (cdiG) is a near-universal bacterial signal that controls the transition from a free-living state to a surface-attached biofilm. However, environmental bacteria have many surface-associated lifestyles distinct from the classic biofilm state. Thus, a grand challenge is to explain how signaling networks utilize only one intracellular output molecule to control diverse adaptations. A recently discovered novel alternative solution has been discovered, based on multiple cyclic dinucleotides that regulate distinct genetic programs. The newfound signal cyclic AMP-GMP (cAG) is required when Geobacter sulfurreducens grows on extracellular metal oxide particles commonly found in sediments and aquifers. In this same organism, the classical signal cdiG is essential for growth as an attached conductive biofilm to relay electrons to methanogens or electrode surfaces. Strikingly, the newfound cAG signaling pathway in Geobacter uses biomolecular parts previously associated with cdiG signaling, revealing cracks in the monolithic model of a cdiG-only signaling network. The sub-class of GGDEF enzymes that synthesize cAG, called DncG, are conserved throughout diverse Bacterial phyla, including Proteobacteria, Acidobacteria, and Deferribacteria. However, regulators of DncG activity and downstream effectors that respond to cAG are largely unknown. This collaborative research project will establish a comprehensive parts map and regulatory model for the newfound cAG signaling pathway, build a molecular toolkit to study how it operates alongside classical cdiG pathways in vivo, and define how the signal controls environmentally important phenotypes.

一些环境细菌具有探测、附着和反应金属颗粒的能力。这一过程导致必需矿物质释放到河流和湖泊中，并降低了正在进行生物修复的废物场地中重金属污染物的毒性。这个合作项目的重点是最近发现的一种机制，使细菌能够感知和响应这些重要的金属。由于这些细菌也能够附着在电极上，监测金属去污的新技术可以利用这些传感系统。研究人员将使用分子技术来观察细菌内部，在那里他们将确定这些金属的传感如何响应不同类型的金属表面来开关基因和蛋白质。该项目将提供跨学科的大学水平的培训，包括在明尼苏达州的经验生物学模块和实习计划服务于社区学院和本科生在加州。作为对K-12学生的推广，我们将调整实践教育演示，展示化学，水质和这种独特的微生物电活动之间的联系。最后，我们将扩展YouSTEM.org，一个由哈蒙德实验室为公众创建的网站，以查找有关免费K-12 STEM项目的信息，以添加明尼阿波利斯/圣保罗地区。循环二GMP（cdiG）是一种近乎普遍的细菌信号，控制从自由生活状态到表面附着生物膜的转变。然而，环境细菌有许多表面相关的生活方式不同于经典的生物膜状态。因此，一个巨大的挑战是解释信号网络如何仅利用一种细胞内输出分子来控制多种适应。最近发现了一种新的替代解决方案，基于调节不同遗传程序的多个环状二核苷酸。新发现的信号环AMP-GMP（cAG）是需要的，当Geetriumsulfreducens生长在细胞外的金属氧化物颗粒通常发现在沉积物和含水层。在这个相同的生物体中，经典信号cdiG对于作为附着的导电生物膜的生长是必不可少的，以将电子中继到产甲烷菌或电极表面。引人注目的是，新发现的cAG信号通路使用了以前与cdiG信号相关的生物分子部分，揭示了仅cdiG信号网络的整体模型中的裂缝。合成cAG的GGDEF酶的亚类，称为DncG，在不同的细菌门中是保守的，包括变形菌门、酸菌门和脱铁菌门。然而，DncG活性的调节剂和对cAG应答的下游效应物在很大程度上是未知的。这项合作研究项目将为新发现的cAG信号通路建立一个全面的部分图谱和调控模型，建立一个分子工具包来研究它如何与经典的cdiG通路在体内一起运作，并定义信号如何控制环境重要的表型。