Microbial communities profoundly influence global biogeochemical cycles and human life. Understanding their wiring is crucial to manage, rationally manipulate, or de novo assemble communities for environmental, industrial or medical applications. However, studying the complex web of microbial interactions and how they are affected by the spatial structure of the community is experimentally challenging. Here, I propose an integrative approach to dissect microbial interactions in a synthetic community consisting of two bacterial species of the human gut microbiota, the commensal Escherichia coli and the probiotic lactic acid bacterium Lactobacillus plantarum. These two species were predicted to engage in exploitative and mutualistic metabolic interactions depending on oxygen availability and provide an experimentally tractable and possibly health-relevant model community. I will employ a combination of highly sensitive quantitative analyses on the molecular level (proteomics, metabolomics, CRISPR/Cas9 genetic perturbations) with quantitative analyses on the individual cell and community level (cellular growth rates and spatial organization) to obtain a comprehensive mechanistic understanding of the interactions between the two species. The multilayered nature of the approach, including the conceptualization of the interactions with a mathematical model, is expected to provide novel insights into the fundamental principles underlying microbial interactions and how they are affected by the environment. Furthermore, a detailed understanding of the molecular interactions of L. plantarum with other gut residents could inform the rational modulation of the gut microbiome to treat diseases associated with dysbiosis. This fellowship would have a major impact on my career by facilitating re-integration into the European research landscape. It would allow me to acquire a unique and competitive scientific profile and to establish my own niche in the field of microbial ecology.
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