Molecular determinants of survival in non-growing bacteria

这个项目将开始回答细菌如何在长期饥饿中生存的根本问题。关于细菌如何生长和繁殖的机制，人们已经知道了很多。相比之下，人们对细菌如何在长时间的营养饥饿中存活下来知之甚少。鉴于自然环境往往是营养贫乏的，这是一个相当大的知识差距。其结果是，细菌被迫保持不生长或生长非常缓慢的状态。细菌是如何在长期饥饿中存活下来的？这种现象的遗传学和生理学基础是什么？当细胞真的死亡时？最常见的死亡原因是什么？拟议的研究将集中在一种名为沼泽红假单胞菌的细菌上，该细菌已被确定为这些研究的良好模型。这种细菌在饥饿的非生长状态下，在实验室中可以存活数周。一项全面的突变计划和高通量DNA测序技术将确定有助于饥饿生存的基因。这些基因将在诱变、实验室研究和基因表达研究的迭代过程中得到验证，并确定它们在饥饿生存中的作用。更广泛的影响。该项目将在微生物功能基因组学方面建立一个用户群。华盛顿大学专注于微生物生物学的18名研究人员将组成这一用户群体的核心。该小组将为数据分析开发新的实验和计算工具，供科学界免费使用。这也将成为培训研究生和本科生将全球系统生物学方法应用于细菌的重点。该用户群体将寻求吸引来自该地区较小学校的教职员工和学生，包括普吉特海湾大学、西雅图太平洋大学、西雅图大学、长荣学院、贝尔维尤社区学院和西雅图社区学院。该项目还将支持一名女性博士后研究员，她将接受培训，整合来自细菌遗传学、生理学和计算分析的数据，以回答有关细胞如何在整个细胞水平上发挥作用的问题。最后，这项研究将有助于更好地理解非生长微生物的作用，这些微生物在自然界中占主导地位，并推动全球碳和氮循环。它还将促进更有效地利用不生长的微生物作为细胞工厂，生产生物燃料等增值产品。

This project will begin to answer the fundamental question of how bacteria survive long-term starvation. A great deal is known about the mechanics of how bacteria grow and multiply. By contrast, little is known about how bacteria survive long periods of nutrient starvation. This is a considerable knowledge gap given that natural environments tend to be nutrient-poor. As a consequence bacteria are forced to persist in a state of non-growth or very slow growth. How do bacteria survive long-term starvation? What is the genetic and physiological basis for this? When cells do die ? what are the most common causes of death? The proposed research will focus on a bacterium named Rhodopseudomonas palustris that has been identified as a good model for these studies. This bacterium stays alive for periods of weeks in a laboratory setting in a starved non-growing state. A comprehensive program of mutagenesis and high throughput DNA sequencing technology will define genes that contribute to starvation survival. These genes will be validated and their role in starvation survival defined in an iterative process of mutagenesis, laboratory studies and gene expression studies. Broader impacts. The project will establish a user group in functional genomics of microbes. A group of eighteen investigators at the University of Washington who focus on microbial biology will form the core of this user group. The group will develop novel experimental and computational tools for data analysis that will be freely available to the scientific community. This will also serve as a focal point to train graduate students and undergraduates to apply global systems biology approaches to bacteria. The user group will seek to engage faculty and students from smaller schools in the area, including University of Puget Sound, Seattle Pacific University, Seattle University, Evergreen College, Bellevue Community College, and the Seattle Community Colleges. This project will also support a female postdoctoral fellow who will be trained to integrate data from bacterial genetics, physiology and computational analyses to answer questions about how cells function at the whole cell level. Finally, this research will lead to a better understanding of the role of non-growing microbes, which dominate in nature, and drive the global carbon and nitrogen cycles. It will also promote more efficient use of non-growing microbes as cell factories for production of value added products like biofuels.