Emergent properties of synthetic microbial consortia

微生物学研究目前正在经历一场革命性的转变，从主要研究单一培养到研究天然和合成微生物群落。微生物群在慢性医学感染和人类肠道微生物群中起着关键作用，并与包括溃疡性结节在内的许多慢性疾病有关。微生物联合体还用于水处理厂、有毒场地修复和生物燃料生产。了解微生物群落对干扰的反应及其随后的控制仍然是一个突出的科学挑战。该项目将向开发分析和建模技术的目标迈出第一步，这些技术将允许合理设计健壮和可控的合成微生物群落。有理论表明，微生物群落的多样化可以增强稳定性、稳健性和提高效率；然而，需要对联合体为其成员提供的优势有一个准确的量化了解。该项目寻求从实验和理论上确定微生物群落中特定代谢相互作用对紧急特性的影响，如增强抗逆性或增加生物量生产。该项目将使用动力系统的工具，如不变流形理论和不变集的稳定性，来分析微生物群落的模型。偏微分方程的方法将被用来将这种分析扩展到相互作用的空间隔离的社区。这些模型将精确地量化定义的微生物相互作用的数量与联合体效率和增强耐受性的改善幅度之间的关系。这将为确定联合行为的特征提供系统生物学基础，并提供一种可扩展的方法来比较加入微生物群落的好处与每个人的成本。这些信息是理解微生物群落持久性的基础，并将为控制有害和可取的联合体提供合理的框架。先前的研究已经在专门的二元群落中与单一栽培相比增加生物量生产的必要条件方面取得了初步结果，并证明了不变流形的存在，这些不变流形简化了对许多类型微生物群落的分析。该项目通过建立具有明确新陈代谢作用的试验性合成群落，测量合成群落的特征，如生物量生产和对扰动的稳健性，以及为更复杂和空间隔离的群落构建数学模型来扩展这项工作。

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.