MIM: Systematic Dissection of Complex Synthetic Gut Bacterial Communities

微生物群落的物种组成是了解其生态功能的关键。虽然已知决定组成的力涉及一个复杂的相互作用网络，但一般规则仍然神秘，部分原因是缺乏具有足够复杂性的模型系统，可以以系统的方式精确调整和实验解剖。该项目将使用100种最常见的肠道微生物的集合，开发和分析具有现实复杂性的肠道微生物群落模型，并在多个尺度上定义组成，量化这些群落对营养扰动的稳健性，并发现形成这些群落最重要的相互作用机制。这项工作很重要，因为微生物群落是地球上几乎每个生态系统的关键组成部分，包括动物肠道的健康功能。该项目还具有教育目标，包括：(1)在当地高中建立外展计划，重点关注微生物分离的新策略；(2)通过设计基于项目的课程，提供理论、计算生物学和生物信息学方面的定量培训；(3)通过与少数族裔服务机构加州大学默塞德分校建立新的合作伙伴关系，并通过一系列研讨会和材料改善研究生录取和招聘实践，扩大代表性不足的少数族裔对微生物学的参与；(4)实施微生物群落建模软件，并向当地高中推广。该项目将结合高通量实验和数学建模，以产生对微生物群落组装和恢复力的机制理解。该研究将干扰稳定的来自粪便样本的体外群落，以确定合成群落对扰动的反应是否与体内相似。至关重要的是，这些已定义的群落能够在群落背景下实现等效的基因型-表型定位，以定量的方式了解种间和菌株-营养相互作用对群落结构和功能的作用，从而实现机制建模。研究人员将参数化粗粒度和分子消费者资源模型，以区分相互作用模式，并预测在单糖、肠道相关代谢物（如玉米粉）和复杂培养基中生长的群落动态。这些结果将为理解营养和菌株-菌株相互作用如何决定微生物群落的组成和稳定性提供一个机制框架。这些科学目标将通过课程开发、外联和其他协同活动获得更广泛的影响。该奖项反映了美国国家科学基金会的法定使命，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。

The species composition of microbial communities is key to understanding their ecological functions. While the forces that determine composition are known to involve a complex network of interactions, general rules remain mysterious in part due to the lack of model systems with sufficient complexity that can be precisely tuned and experimentally dissected in a systematic fashion. This project will use a collection of the 100 most common gut microbes, to develop and analyze models of gut microbial communities of realistic complexity, yet defined composition at multiple scales, quantify the robustness of these communities to nutrient perturbations, and discover the interaction mechanisms most important for shaping these communities. This work is important because microbial communities are critical components of practically every ecosystem on the planet, including the healthy functioning of the guts of animals. This project also has educational goals, including: (1) to establish outreach programs at local high schools focused on a novel strategy for microbial isolation; (2) to provide quantitative training in theory, computational biology, and bioinformatics through the design of a project-based course; (3) to broaden participation of underrepresented minorities in microbiology through a novel partnership with UC Merced, a minority-serving institution, and via improving practices in graduate student admission and hiring practices through a series of workshops and materials; (4) to implement software for modeling microbial communities that is disseminated to local high schools. This project will combine high-throughput experimentation and mathematical modeling to produce a mechanistic understanding of the assembly and resilience of microbial communities. The research will perturb stable in vitro communities derived from fecal samples to ascertain whether the synthetic communities respond similarly to perturbations as in vivo. Critically, these defined communities enable the equivalent of genotype-phenotype mapping in a community context, to understand the roles of interspecies and strain-nutrient interactions on community structure and function in a quantitative manner that enables mechanistic modeling. Researchers will parameterize coarse-grained and molecular consumer-resource models to distinguish between modes of interaction and predict community dynamics, during growth in simple sugars, gut-relevant metabolites such as corrinoids, and complex media. The results will provide a mechanistic framework for understanding how nutritional and strain-strain interactions dictate the composition and stability of microbial communities. These scientific goals will be supplemented with broader impact achieved through course development, outreach, and other synergistic activities.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.