Regulatory Signaling Logic In Self-Assembled Microbial Communities During Oscillating Environmental Conditions

振荡环境条件下自组装微生物群落的调节信号逻辑

• 批准号: 1518130
• 负责人: Katherine McMahon
• 金额: $ 69.59万
• 依托单位: University of Wisconsin-Madison
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1518130&HistoricalAwards=false
• 关键词: Regulatory; Signaling; Logic; Self; Assembled

Scientists using new techniques based on DNA sequencing are now able to study how bacteria thrive in many different conditions. This is important because bacteria are much simpler and easier to study than other life forms such as plants and animals, and much of what is learned using bacteria can be applied to other types of organisms. However, most research involves studies of bacteria living in isolation in the laboratory. Very few organisms live in isolation in nature, and therefore it is important to develop research methods to study bacteria living in communities. The research will show how genes and other component parts of the bacteria work together in order to sustain life and especially how these interactions help bacteria survive in harsh and rapidly changing situations. The results of this research will help predict how organisms can adapt and survive when their surroundings change to less hospitable conditions. The project is anticipated to have applications in many different areas including the study of bacteria that live in and on the human body, the design and control of pollution clean-up systems, and acquisition of fundamental knowledge of how organisms in aquatic environments survive and thrive.This project will provide interdisciplinary training to students (undergraduate and graduate) and postdoctoral fellows in engineering, microbiology, biotechnology and computational biology, in the context of both academic research and industrial applications. A primary goal of systems biology is to develop a quantitative understanding of how microorganisms respond to changing conditions. Therefore, it is important to understand the molecular and regulatory "wiring diagrams" that enable unculturable organisms to thrive in dynamic environments. One such group of unculturable organisms,the biotechnologically-relevant group of bacteria (Accumulibacter), combines metabolic and regulatory processes in different ways to yield novel phenotypes in response to environmental stimuli. Accumulibacter is a well-studied yet uncultivated microbe. It must constantly adapt its global physiological response to changing environmental stresses, namely biphasic cycles of anaerobic "feast" and aerobic "famine" conditions. These oscillating conditions select strongly for the Accumulibacter phenotype, which includes the ability to sequester massive amounts of carbon and phosphate intracellularly in different phases of the cycle. However, the regulatory and metabolic network dynamics that coordinate such precise transitions remain poorly understood. Employing a variety of -omics techniques and a systems biology framework within the context of a tractable and self-assembled microbial community, studies will: 1) identify the metabolic modules responsible for Accumulibacter's unique physiology via comparative genomics and transcriptomics; 2) map the regulons that coordinate Accumulibacter's storage response via ChIP-seq targeting candidate regulatory elements; and 3) identify environmental drivers of Accumulibacter's regulatory program.

科学家们使用基于DNA测序的新技术，现在能够研究细菌如何在许多不同的条件下茁壮成长。这一点很重要，因为细菌比其他生命形式（如植物和动物）更简单，更容易研究，而且使用细菌所学到的大部分知识可以应用于其他类型的生物体。然而，大多数研究涉及在实验室中隔离生活的细菌的研究。在自然界中，很少有生物是孤立生活的，因此，重要的是要开发研究方法来研究生活在社区中的细菌。这项研究将展示基因和细菌的其他组成部分如何共同工作以维持生命，特别是这些相互作用如何帮助细菌在恶劣和快速变化的情况下生存。这项研究的结果将有助于预测生物如何适应和生存时，他们的环境变化到不那么好客的条件。该项目预计将在多个不同领域应用，包括研究生活在人体内和人体表面的细菌、设计和控制污染清理系统，以及获得水生环境中生物如何生存和繁殖的基本知识。该项目将为学生提供跨学科培训工程、微生物学、生物技术和计算生物学方面的研究生（本科生和研究生）和博士后研究员，从事学术研究和工业应用。系统生物学的一个主要目标是定量地了解微生物如何对变化的条件作出反应。因此，重要的是要了解分子和监管的“布线图”，使不可培养的生物体在动态环境中茁壮成长。一组这样的不可培养的生物体，生物技术相关的细菌组（Accumulibacter），以不同的方式结合代谢和调节过程，以产生新的表型响应环境刺激。Accumulibacter是一种研究充分但尚未培养的微生物。它必须不断调整其整体生理反应，以适应不断变化的环境压力，即厌氧“盛宴”和有氧“饥饿”条件的双相循环。这些振荡条件强烈地选择了Accumulibacter表型，其包括在循环的不同阶段中在细胞内螯合大量碳和磷酸盐的能力。然而，协调这种精确转换的调节和代谢网络动力学仍然知之甚少。 在易处理和自组装的微生物群落的背景下，采用多种组学技术和系统生物学框架，研究将：1）通过比较基因组学和转录组学鉴定负责Accumulibacter独特生理学的代谢模块; 2）通过ChIP-seq靶向候选调控元件定位协调Accumulibacter储存反应的调节子;和3）确定Accumulibacter监管计划的环境驱动因素。