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

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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. In this project, we will take advantage of tractable synthetic yeast communities and mathematical modelling to experimentally and theoretically study the origin and evolution of metabolic interactions.We will undertake a fully integrated, collaborative approach that combines the expertise of US and UK groups on metabolic modeling, synthetic biology, and microbial ecology and evolution. First, we will use statistical thermodynamics and differential equations to model metabolic overflows. Next, we will experimentally characterize metabolic overflows as well as key cellular parameters using targeted metabolomics, fluorescence microscopy, and single cell electrochemical measurements. We will use these experimental results to constrain, test, and refine the model. We will then embed the tested model within an in silico evolution framework to simulate evolution, and predict how initial community conditions (e.g. nutrient environment, genotypes, and initial species interactions) will affect the evolution of new metabolic interactions, as we have observed in preliminary work. Finally, we will test model predictions by evolving synthetic yeast communities from these different starting conditions in chemostats and turbidostats, and characterize emerging metabolic interactions.