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

使用基于DNA测序的新技术的科学家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简单得多，也更容易研究，而且通过细菌学到的很多东西都可以应用于其他类型的有机体。然而，大多数研究涉及在实验室中隔离生活的细菌的研究。很少有生物在自然界中与世隔绝地生活，因此开发研究方法来研究群落中的细菌是很重要的。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环境中生存。这项研究的结果将有助于预测当环境变化到不太适宜居住的条件时，生物体如何适应和生存。该项目预计将在许多不同的领域得到应用，包括研究生活在人体内和体内的细菌，设计和控制污染净化系统，以及获得关于水环境中生物如何生存和繁衍的基本知识。该项目将在学术研究和工业应用的背景下，为工程、微生物学、生物技术和计算生物学的学生(本科生和研究生)和博士后研究员提供跨学科培训。系统生物学的一个主要目标是发展对微生物如何对不断变化的条件作出反应的定量理解。因此，重要的是要理解使不可培养的有机体在动态环境中茁壮成长的分子和调控“接线图”。其中一组不可培养的生物体是与生物技术相关的细菌组(Acumulibacter)，它们以不同的方式结合新陈代谢和调节过程，以产生新的表型来响应环境刺激。Acumulibacter是一种研究得很好但尚未培养的微生物。它必须不断调整其全球生理反应，以适应不断变化的环境压力，即无氧“盛宴”和有氧“饥荒”条件的两相循环。这些振荡条件强烈地选择了Acumulibacter的表型，包括在循环的不同阶段将大量的碳和磷隔离在细胞内的能力。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。在一个易于处理和自我组装的微生物群落的背景下，利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Acumulibacter独特生理的代谢模块；2)通过针对候选调节元件的芯片序列绘制协调Acumulibacter储存反应的调节因子；以及3)确定Acumulibacter调节计划的环境驱动因素。

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.