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

微生物群落对于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，因为有益的微生物有助于消化食物，调节免疫力，并抵御入侵的病原体。群落中的每一种微生物都会使用环境中的某些化合物，通常微生物会释放出新的化合物，供群落中的其他成员使用。这些“代谢相互作用”影响到个体物种的生存和整个微生物群落的稳定性。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物种而发展和变化的，以及这些相互作用如何改变群落的稳定性和组成。最终，该项目旨在揭示用于环境修复等目的的微生物群落设计原则。该项目的参与者将包括高中教师、未被充分代表的少数民族高中生和未被充分代表的少数民族本科生。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的循环方面发挥着关键作用。物种之间的代谢相互作用影响群落的功能和稳定性。然而，人们对代谢相互作用的出现和演变知之甚少。参与该项目的实验室将利用易于处理的合成酵母群落和数学建模来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、协作的方法，将两个小组在代谢建模、合成生物学以及微生物生态和进化方面的专业知识结合起来。首先，将使用统计热力学和微分方程式对代谢溢出进行建模。接下来，将使用靶向代谢组学、荧光显微镜和单细胞电化学测量对代谢溢出以及关键细胞参数进行实验表征。这些实验测量将用于约束、测试和改进模型。被测试的模型将被嵌入到电子进化框架中，以模拟进化，并预测初始群落条件(如营养环境、基因类型和物种相互作用)可能如何影响新的新陈代谢相互作用的进化。最后，模型预测将通过在恒化器和浊度器中从不同的起始条件进化的合成酵母群落来验证，并将表征新出现的代谢相互作用。这一美英合作项目得到了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的支持。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。

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.