MODULUS: Modulation of microbial community dynamics by spatial partitioning

微生物在自然界中无处不在。它们存在于每一个可以想象到的栖息地，形成复杂的群落，执行各种功能，使它们能够调节影响从人类健康到环境和生物技术应用等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、竞争或合作以获得资源或科普压力来进行交流和相互作用。这些无数的相互作用提出了几个基本问题，关于形成微生物群落的功能和稳定性的进化和生态力量。利用微生物群落通常被划分为在组成和局部相互作用方面不同的子群落的观察，研究人员使用工程微生物财团的数学建模和实验分析的组合来探索空间分区和维护生物多样性和功能的基本机制。作为该项目的结果开发的分子到社区规模的数学模型将用于发现与微生物的空间分区和相互作用到微生态规模表型和动态相关的可推广的规则。 这些见解可以形成控制合成微生物聚生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机会，通过“蓝魔耐药基因组项目”参与跨学科研究，这是一个为期一年的动手项目，涉及学生在整个杜克大学校园内收集，调查和分析环境细菌。在阐明微生物群落的功能和动态方面已经取得了广泛的进展，主要依赖于面向调查的方法（例如，自然群落的测序分析）。虽然这些研究已经产生了关于微生物群落的组成以及组成如何与环境条件相关的见解，但它们对微生物群落的维持和功能提供了有限的机制见解。迄今为止，解决这个问题的努力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。该项目探索了微生物组组织和功能中的一个全球性但未被充分认识的因素，即微生物群落划分为孤立或半孤立的局部社区。分区通常来自特定环境中的空间隔离，例如不同土壤颗粒大小导致的肠道或土壤微生物组中的微生态位的空间分区。研究人员使用合成生物学和微流控方法来设计不同空间分区的合作或竞争社区，并采用系统和生态驱动的数学建模来探索空间分区如何差异化地影响由竞争性，合作性或合作性和竞争性物种的复杂混合物组成的工程合成财团。 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功能和维护，该项目的结果将有助于发现管理生物多样性的基本原则，各种生物环境中微生态位的出现，并为合成微生物财团的发展提供设计规则和限制。该奖项由分子与细胞生物科学部的系统与合成生物学和数学科学部的数学生物学项目共同资助。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值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.