Periodic Reporting for period 3 - ModEM (Model-guided Engineering of Complex Microbial Communities)
Berichtszeitraum: 2023-10-01 bis 2025-03-31
Microbial communities occupy practically all habitats on Earth, from ocean deeps to the human gut, and are pivotal to the ecosystem function. They also hold a vast biotechnological potential to realize functionalities typically beyond the reach of single species, e.g. valorisation of complex resources. Rational design and modulation of communities can thus help addressing outstanding challenges in health and bio-sustainability. Yet, this remains difficult due to the complexity of interspecies interactions. The overarching goal of the ModEM project is to combine mathematical modelling, genetics, omics and laboratory evolution to identify new ways to modulate complex microbial communities. Kefir, a natural milk-fermenting community, and stable assemblies of human gut bacteria are being used as two model systems. The results will have fundamental implications for modulating microbial communities relevant for environment, health and biotechnology.
On the computational front, we have developed a mathematical framework to simulate how complex communities respond to introduction of new species or change in their nutritional environment. The models are validated using experimental data on in vitro gut bacterial communities. We have also developed genome-scale metabolic models for representative gut bacterial species capturing their metabolic capabilities and using these to simulate metabolic competition and cooperation. On the experimental front, the project scientists have created genetic libraries for a highly abundant and prevalent but understudied gut bacterial species. In addition, we have established high-throughput methods to measure metabolites that play key roles in mediating bacteria-host interactions. In summary, the project thus far has developed the key tools and methodologies required for fulfilling the main goals.
The project has developed new integrated computational-experimental methods to decipher metabolite flow in microbial communities. This is a significant step towards understanding dynamics and function of microbial communities, going beyond cataloguing the presence of certain microbes. Based on the planned next steps, we expect to create models that can predict the fate of new species introduced in an established community, e.g. gut microbiota, and validate some predictions using laboratory experiments. Overall, we expect these results to contribute towards developing new microbial solutions in the fermented food and gut microbiome sector.