MIM: Systematic Dissection of Complex Synthetic Gut Bacterial Communities

MIM：复杂合成肠道细菌群落的系统解剖

• 批准号: 2125383
• 负责人: Kerwyn Huang
• 金额: $ 250万
• 依托单位: Stanford University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2125383&HistoricalAwards=false
• 关键词: MIM; Systematic; Dissection; Complex; Synthetic

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.

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复杂的相互作用网络，但一般规则仍然是神秘的，部分原因是缺乏足够复杂的模型系统，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，但在多个尺度上定义组成，量化这些群落对营养扰动的鲁棒性，并发现对塑造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。该项目也有教育目标，包括：（1）在当地高中建立外展计划，重点是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的定量培训;（3）通过与为少数群体服务的机构加州大学默塞德分校建立新的伙伴关系，扩大代表性不足的少数群体对微生物学的参与，并通过一系列的研讨会和材料来改善研究生入学和招聘的做法;（4）实施软件来模拟微生物群落，并将其分发给当地高中。该项目将结合联合收割机高通量实验和数学建模，以产生对微生物群落的组装和恢复力的机械理解。该研究将扰动来自粪便样本的稳定的体外群落，以确定合成群落是否对体内扰动做出类似的反应。至关重要的是，这些定义的社区，使相当于在社区背景下的基因型-表型映射，了解物种间和菌株-营养相互作用对社区结构和功能的作用，以定量的方式，使机械建模。研究人员将参数化粗粒度和分子消费者资源模型，以区分相互作用的模式，并预测社区动态，在单糖，肠道相关代谢物（如corrinoids）和复杂介质中生长。这些结果将为理解营养和菌株间的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、推广和其他协同活动产生更广泛的影响来补充。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。

项目成果

Human metabolome variation along the upper intestinal tract.

• DOI: 10.1038/s42255-023-00777-z
• 发表时间: 2023-05
• 期刊: NATURE METABOLISM
• 影响因子: 20.8
• 作者: Folz, Jacob;Culver, Rebecca Neal;Morales, Juan Montes;Grembi, Jessica;Triadafilopoulos, George;Relman, David A.;Huang, Kerwyn Casey;Shalon, Dari;Fiehn, Oliver
• 通讯作者: Fiehn, Oliver

Competition for fluctuating resources reproduces statistics of species abundance over time across wide-ranging microbiotas.

• DOI: 10.7554/elife.75168
• 发表时间: 2022-04-11
• 期刊: ELIFE
• 影响因子: 7.7
• 作者: Ho, Po-Yi;Good, Benjamin H.;Huang, Kerwyn Casey
• 通讯作者: Huang, Kerwyn Casey

Modulation of antibiotic effects on microbial communities by resource competition.

• DOI: 10.1038/s41467-023-37895-x
• 发表时间: 2023-04-26
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Newton, Daniel P.;Ho, Po-Yi;Huang, Kerwyn Casey
• 通讯作者: Huang, Kerwyn Casey