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.

使用基于DNA测序的新技术的科学家现在能够研究细菌在许多不同条件下如何繁殖。这很重要，因为细菌比其他生命形式（例如动植物）更简单，更容易学习，并且使用细菌学到的许多东西可以应用于其他类型的生物。但是，大多数研究涉及对实验室孤立的细菌研究。很少有生物在本质上生活在孤立状态，因此，开发研究居住在社区中的细菌很重要。该研究将展示细菌的基因和其他组成部分如何共同起作用以维持生命，尤其是这些相互作用如何帮助细菌在严酷且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体在周围环境变化为好客的情况下如何适应和生存。预计该项目将在许多不同领域中应用，包括研究人体和人体上的细菌，污染清理系统的设计和控制，以及对水生环境中生物的基本知识的获取，该项目将向学生提供跨学科的培训。学术研究和工业应用。系统生物学的主要目标是对微生物如何应对变化的状况做出定量理解。因此，重要的是要了解使无法培养的生物在动态环境中繁衍生长的分子和调节性“接线图”。这样的一组不可培养的生物是与生物技术相关的细菌（累积），以不同的方式结合了代谢过程和调节过程，以产生新的表型，以响应环境刺激。蓄积是一种经过良好研究的微生物。它必须不断使其全球生理反应适应不断变化的环境压力，即厌氧“盛宴”和有氧“饥荒”条件的双相周期。这些振荡条件强烈选择了累积表型，其中包括能够在周期的不同阶段隔离大量碳和磷酸盐的能力。但是，协调此类精确过渡的调节和代谢网络动力学仍然知之甚少。 在可牵引和自组装的微生物群落的背景下采用各种 - 组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确定负责累积的独特生理学的代谢模块； 2）绘制通过芯片seq靶向候选调节元素来协调累积的存储响应的调节； 3）确定累积监管计划的环境驱动力。