MODULUS: Modulation of microbial community dynamics by spatial partitioning

微生物在自然界中无处不在。它们存在于任何可以想象到的栖息地，形成复杂的群落，执行不同的功能，使它们能够调节影响从人类健康到环境和生物技术应用的广泛生物领域的系统。微生物群落的成员通过产生和响应信号分子、交换遗传物质以及竞争或合作来获得资源或应对压力来进行交流和互动。这些千头万绪的相互作用提出了几个基本问题，涉及塑造微生物群落功能和稳定性的进化和生态力量。利用微生物群落经常被划分为在组成和局部相互作用方面不同的子群落这一观察结果，研究人员使用工程微生物群落的数学建模和实验分析相结合的方法来探索空间划分和维持生物多样性和功能的基本机制。作为该项目的结果而开发的分子到群落尺度的数学模型将被用来发现将微生物的空间划分和相互作用与微生态尺度、表型和动力学联系起来的普遍规则。这样的见解可以形成管理合成微生物联合体的开发和使用的设计原则的基础。该项目还将为本科生和研究生提供参与跨学科研究的机会，这是一个为期一年的亲身实践项目，让学生参与杜克大学校园内环境细菌的收集、调查和分析。在阐明微生物群落的功能和动态方面取得了广泛进展，主要依靠以调查为导向的方法(例如，对自然群落进行测序分析)。虽然这些研究对微生物群落的组成以及组成与环境条件的关系有了深入的了解，但它们对微生物群落的维护和功能提供了有限的机械性见解。迄今为止，解决这一问题的努力主要集中在微生物如何相互作用以及这种相互作用如何塑造整个群落的动态和功能。这个项目探索了微生物组组织和功能中的一个全球性的、但未得到充分认识的因素，即将微生物群落划分为孤立或半隔离的本地群落。在特定的环境中，土壤微生物群落中的肠道或微生态位通常是由于土壤颗粒大小不同而产生的空间分离。研究人员使用合成生物学和微流体方法来设计不同空间分区的合作或竞争群落，并使用系统和生态驱动的数学模型来探索空间分区如何不同地影响由竞争、合作或复杂的合作和竞争物种混合物组成的工程合成联合体。随着微生物生态学领域从表征自然微生物群落的结构转向确定群落的功能和维护，该项目的结果将有助于发现支配生物多样性的基本原理，各种生物环境中微生态位的出现，并为制定设计规则和限制合成微生物联合体的发展提供信息。该奖项是由分子和细胞生物科学部的系统和合成生物学以及数学科学部的数学生物学项目共同资助的。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Microbes are ubiquitous in nature. Existing in every imaginable habitat, they form complex communities that carry out diverse functions enabling them to modulate systems that impact a wide swath of biological domains ranging from human health to environmental and biotechnological applications. Members of microbial communities communicate and interact by producing and responding to signaling molecules, exchanging genetic materials, and competing or collaborating to gain resources or cope with stress. These myriad of interactions raise several fundamental questions regarding the evolutionary and ecological forces that shape the function and stability of microbial communities. Leveraging the observation that a microbial community is often partitioned into sub-communities that differ with respect to composition and local interactions, investigators use a combination of mathematical modeling and experimental analysis of engineered microbial consortia to explore the fundamental mechanisms underlying spatial partitioning and maintenance of biodiversity and function. Molecular to community scale mathematical models developed as a result of the project will be used to discover generalizable rules relating spatial partitioning and interactions of microbes to microecological scale phenotypes and dynamics. Such insights can form the foundation of design principles that govern the development and use of synthetic microbial consortia. The project will also provide opportunities for undergraduates and graduate students to participate in interdisciplinary research through the "The Blue Devil Resistome Project", a hands on one-year project that involves students in the collection, survey, and analysis of environmental bacteria across the Duke University campus. Extensive progress has been made in elucidating the function and dynamics of microbial communities, primarily relying on survey-oriented approaches (e.g., sequencing analysis of natural communities). While these studies have generated insight regarding the composition of microbial communities and how composition correlates with environmental conditions, they offer limited mechanistic insights into the maintenance and function of microbial communities. To date, efforts to address this question have focused on how microbes interact and how such interactions shape the dynamics and function of the overall community. This project explores a global, yet underappreciated, factor in microbiome organization and function, the partitioning of a microbial community into isolated or semi-isolated local communities. Partitioning often arises from spatial segregation in a given environment, such as spatial partitioning of the gut or microecological niches in the soil microbiome resulting from different soil particle sizes. Investigators use synthetic biology and microfluidic methods to engineer cooperative or competitive communities of varying spatial partitions, and employ systems and ecologically driven mathematical modeling to explore how spatial partitioning differentially impacts engineered synthetic consortia composed of competitive, cooperative, or complex mixtures of cooperative and competitive species. As the field of microbial ecology shifts from characterizing the structure of natural microbial communities to determination of community function and maintenance, results from this project will contribute to the discovery of fundamental principles that govern biodiversity, the emergences of microecological niches in various biological environments, and inform the development of design rules and constraints for the development of synthetic microbial consortia. This award was co-funded by Systems and Synthetic Biology in the Division of Molecular and Cellular Biosciences and the Mathematical Biology Program of the Division of Mathematical Sciences.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.