Emergent properties of synthetic microbial consortia

合成微生物群落的新兴特性

• 批准号: 1361240
• 负责人: Tomas Gedeon
• 金额: $ 74.56万
• 依托单位: Montana State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1361240&HistoricalAwards=false
• 关键词: Emergent; properties; synthetic; microbial; consortia

Microbiology research is currently undergoing a revolutionary transition from the study of primarily monocultures to the study of natural and synthetic microbial communities. Microbial consortia play a key role in chronic medical infections and the human gut microbiome and have been implicated in many chronic medical conditions including ulcerative colitus. Microbial consortia are also used in water treatment plants, toxic site remediation and biofuel production. Understanding the behavior of microbial communities in response to a disturbance and their subsequent control remains an outstanding scientific challenge. This project will provide a first step toward the goal of developing analytic and modeling techniques that will allow rational design of synthetic microbial communities that are robust and controllable. There are theories suggesting that diversification in a microbial community may enhance stability, robustness and increase efficiency; however a precise quantitative understanding of the advantages that a consortium provides for its members is needed. This project seeks to experimentally and theoretically determine the impact of specific metabolic interactions within a microbial community on emergent properties like enhanced stress tolerance or increased biomass production. The project will use tools of dynamical systems, like invariant manifold theory and stability of invariant sets, to analyze models of microbial communities. Methods of partial differential equations will be used to extend this analysis to interacting spatially segregated communities. These models will precisely quantify the relationship between the number of defined microbial interactions and the magnitude of improvement on both consortia efficiency and enhanced tolerance. This will provide a systems biology basis for characterizing consortial behaviors and a scalable methodology to compare the benefits of membership in a microbial community to the costs for each individual. This information is fundamental to understanding microbial community persistence and will provide a rational framework for controlling both unwanted and desirable consortia. Prior research has yielded preliminary results on the conditions necessary for increased biomass production in specialized binary communities versus a monoculture and has demonstrated the existence of invariant manifolds that simplify the analysis for many types of microbial communities. This project extends this work by building experimental synthetic communities with well-defined metabolic roles, measuring the synthetic community's characteristics like biomass production and robustness to perturbations and constructing mathematical models for more complex and spatially segregated communities.

微生物学研究目前正在革命性的转变，从主要的单一培养研究到自然和合成微生物群落的研究。 微生物财团在慢性医学感染和人类肠道微生物组中起关键作用，并且已与包括溃疡性Colitus在内的许多慢性医疗状况有关。微生物财团还用于水处理厂，有毒部位的修复和生物燃料生产。了解微生物群落对干扰及其后续控制的行为仍然是一个杰出的科学挑战。该项目将为开发分析和建模技术的目标提供第一步，该技术将允许合理设计合成的微生物群落，这些群落可靠且可控制。有一些理论表明，微生物群落中的多元化可能会提高稳定性，稳健性和提高效率。但是，需要对财团为其成员提供的优势进行确切的定量理解。该项目旨在通过实验和理论上确定微生物群落中特定代谢相互作用对新出现特性（例如增强的胁迫耐受性或增加生物量产生）的影响。该项目将使用动态系统的工具，例如不变的流形理论和不变集的稳定性来分析微生物群落模型。部分微分方程的方法将用于将此分析扩展到空间隔离的社区。 这些模型将精确地量化定义的微生物相互作用数量与伴侣效率和增强公差的改善幅度之间的关系。这将提供一个系统生物学基础，以表征联盟行为和一种可扩展的方法，以将微生物社区成员的好处与每个人的成本进行比较。这些信息对于理解微生物社区的持久性至关重要，并将提供一个合理的框架来控制不必要的和理想的财团。先前的研究已经在专业二元社区中增加生物量生产所必需的条件与单一文化相对于单一文化产生了初步结果，并证明了存在不变的流形的存在，从而简化了许多类型的微生物群落的分析。该项目通过建立具有明确定义的代谢角色的实验合成社区来扩展这项工作，从而衡量合成社区的特征，例如生物量生产和稳健性对扰动，并为更复杂和空间分离的社区构建数学模型。