BBSRC-NSF/BIO: Understanding the origin and evolution of metabolic interactions using synthetic microbial communities

微生物群落对许多环境过程至关重要，例如从死亡有机物的降解中释放营养物质。微生物群落对健康也很重要，因为有益微生物有助于消化食物、调节免疫力和抵御入侵的病原体。群落中的每一种微生物都使用环境中可用的某些化合物，并且微生物通常会释放出新的化合物，供群落的其他成员使用。这些“代谢相互作用”影响着个体物种的生存和整个微生物群落的稳定。这个合作项目的目标是更好地了解这些相互作用是如何根据环境和群落中的微生物种类而发展和变化的，以及这些相互作用是如何改变群落的稳定性和组成的。最终，该项目旨在揭示微生物群落的设计原则，用于环境修复等目的。该项目的参与者将包括高中教师、少数族裔高中生和少数族裔本科生。微生物群落无处不在，在调节宿主健康和疾病以及生态系统中元素循环方面发挥着关键作用。物种间的代谢相互作用影响着群落的功能和稳定性。然而，代谢相互作用的出现和进化却知之甚少。参与该项目的实验室将利用可处理的合成酵母群落和数学模型，从实验和理论上研究代谢相互作用的起源和进化。他们将采取一种完全整合的合作方式，结合两个小组在代谢建模、合成生物学、微生物生态学和进化方面的专业知识。首先，统计热力学和微分方程将用于模拟代谢溢出。接下来，代谢溢出以及关键的细胞参数将使用靶向代谢组学、荧光显微镜和单细胞电化学测量进行实验表征。这些实验测量将用于约束、测试和完善模型。测试的模型将嵌入到一个模拟进化的计算机进化框架中，并预测初始群落条件（如营养环境、基因型和物种相互作用）如何影响新的代谢相互作用的进化。最后，模型预测将通过进化合成酵母群落在不同的初始条件下在化学调节剂和浊度调节剂中进行测试，并将描述新出现的代谢相互作用。这个英美合作项目由美国国家科学基金会和英国生物技术和生物科学研究委员会支持。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。

Microbial communities are critically important for many environmental processes such as the release of nutrients from the degradation of dead organic matter. Microbial communities are also important for health, as beneficial microbes help digest food, modulate immunity, and fend off intruding pathogens. Each species of microbe in the community uses certain compounds available in the environment and often the microbes release new compounds that other members of the community can use. These "metabolic interactions" impact the survival of individual species and the stability of the microbial community as a whole. The goal of this collaborative project is to better understand how these interactions develop and change depending on the environment and microbial species in the community, and how these interactions change the stability and composition of the communities. Ultimately, this project aims to reveal principles for the design of microbial communities for purposes such environmental remediation. Participants on this project will include high school teachers, underrepresented minority high school students, and underrepresented minority undergraduates. Microbial communities are ubiquitous, and are critical players in mediating host health and disease and in the cycling of elements in ecosystems. Metabolic interactions between species impact community function and stability. However, the emergence and evolution of metabolic interactions is poorly understood. The laboratories involved in this project will take advantage of tractable synthetic yeast communities and mathematical modeling to experimentally and theoretically study the origin and evolution of metabolic interactions. They will undertake a fully integrated, collaborative approach that combines the expertise of both groups on metabolic modeling, synthetic biology, and microbial ecology and evolution. First, statistical thermodynamics and differential equations will be used to model metabolic overflows. Next, metabolic overflows as well as key cellular parameters will be experimentally characterized using targeted metabolomics, fluorescence microscopy, and single cell electrochemical measurements. These experimental measurements will be used to constrain, test, and refine the model. The tested model will be embedded within an in silico evolution framework to simulate evolution, and to predict how initial community conditions (e.g. nutrient environment, genotypes, and species interactions) might affect the evolution of new metabolic interactions. Finally, model predictions will be tested by evolving synthetic yeast communities from different starting conditions in chemostats and turbidostats, and emerging metabolic interactions will be characterized.This collaborative US/UK project is supported by the US National Science Foundation and the UK Biotechnology and Biological Sciences Research Council.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.