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Model-guided Engineering of Complex Microbial Communities

Project description

Community outreach, microbial style

Life on Earth is likely to have originated from single-celled organisms that appeared three billion years ago in our first oceans. It took more than two billion more years for an eruption of more complex life forms that, to this day, rely strongly on microbial communities for the function of the ecosystems in which they live. These communities offer unprecedented potential to produce natural ingredients we can harness for sustainable applications in medicine, energy, environmental science and more. However, understanding complex interspecies interactions is a tremendous challenge. The EU-funded ModEM project is beginning to untangle the interconnections through the application of advanced techniques in modelling, genetics, omics and more. Enhanced understanding could help build microbial communities that enhance the secretion of metabolites that help them thrive.

Objective

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. Towards tackling this, I plan to combine modelling, genetics, omics and laboratory evolution to study complex microbial communities with a focus on metabolic cross-feeding. Kefir, a natural milk-fermenting community, and stable assemblies of human gut bacteria will be used as two model systems. Both systems have recently been pioneered by my lab and represent complexity relevant for real-world applications. We will first investigate the genetic and environmental factors driving metabolite secretion using high-throughput screening of natural isolates and genetic libraries. Large-scale pairwise interaction mapping and self-establishing stable sub-communities will be used to unravel higher-order interactions and to discover the principles of community assembly. Laboratory evolution will then be used to assess community stability as well as to decipher interaction mechanisms through multi-omics analyses. The experimental data on species metabolism and interspecies interactions will be used to build hybrid metabolic-ecological models for predicting effects of perturbations like species introduction and nutrient change. The applicability will be demonstrated through stable introduction of probiotic species in personalized gut bacterial communities, and by developing vitamin overproducing milk fermenting communities. The results will have fundamental implications for modulating microbial communities relevant for environment, health and biotechnology.

Host institution

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Net EU contribution
€ 1 995 818,00
Address
TRINITY LANE THE OLD SCHOOLS
CB2 1TN Cambridge
United Kingdom

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Region
East of England East Anglia Cambridgeshire CC
Activity type
Higher or Secondary Education Establishments
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Total cost
€ 1 995 818,00

Beneficiaries (1)