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

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，因为细菌比植物和动物等其他生命形式更简单，更容易研究，而且从细菌中学到的许多知识也可以应用于其他类型的生物体。然而，大多数研究涉及对实验室中孤立生活的细菌的研究。自然界中很少有生物是孤立生活的，因此开发研究细菌群落生活的研究方法是很重要的。这项研究将揭示基因和细菌的其他组成部分如何共同作用以维持生命，特别是这些相互作用如何帮助细菌在恶劣和快速变化的环境中生存。这项研究的结果将有助于预测生物如何适应和生存，当他们的环境变化到不适宜生存的条件。该项目预计将应用于许多不同的领域，包括研究生活在人体内外的细菌，污染清理系统的设计和控制，以及获取水生环境中生物如何生存和繁衍的基本知识。该项目将为工程、微生物学、生物技术和计算生物学方面的学生（本科生和研究生）和博士后提供跨学科的培训，包括学术研究和工业应用。系统生物学的一个主要目标是发展对微生物如何对变化的条件作出反应的定量理解。因此，了解使不可培养的生物体在动态环境中茁壮成长的分子和调控“接线图”是很重要的。其中一组不可培养的生物，生物技术相关的细菌群（Accumulibacter），以不同的方式结合代谢和调节过程，以响应环境刺激产生新的表型。蓄积杆菌是一种被充分研究但尚未被培养的微生物。它必须不断适应不断变化的环境压力的全球生理反应，即厌氧“盛宴”和有氧“饥荒”条件的双相循环。这些振荡条件强烈地选择了Accumulibacter表型，其中包括在循环的不同阶段在细胞内隔离大量碳和磷酸盐的能力。然而，协调这种精确转变的调节和代谢网络动力学仍然知之甚少。在可处理和自组装的微生物群落背景下，采用各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确定负责Accumulibacter独特生理的代谢模块；2)通过靶向候选调控元件的ChIP-seq绘制协调Accumulibacter储存反应的调控；3)确定Accumulibacter调控程序的环境驱动因素。

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.