Modelling microbiome dynamics in continuous culture

• Applicant: Professorin Dr. Ruth Anne Schmitz-Streit
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms ; Bioinformatics and Theoretical Biology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 546086244

Over the past decade, advances in DNA-sequencing methodologies have revolutionised microbiome research, facilitating the genomic characterisation of diverse microbial communities. These advances have unveiled the novelty, complexity, and functional repertoire of microbes, while also highlighting the role of microbiota in both health and disease of humans, animals, and plants. However, studies have largely focused on descriptive differences between two or more conditions and not analysed causality due to inherent experimental limitations, such as the complexity of host-associated microbial communities and large variation between individuals/samples. Nevertheless, well-studied communities have provided a nascent picture of a representative microbial community. Coupled with the recent large-scale efforts to cultivate microbes, there now exist isolates for a large fraction of the most abundant members of said community, facilitating the construction of synthetic communities (SynComs). Most SynComs generated so far have been grown in batch cultures (fixed volume, rich medium), where the microbes are grown for a short time until they reach stationary growth phase. To overcome this limitation and study complex communities under conditions more closely mimicking the natural environment, we propose to develop a continuous culturing system using the most sophisticated human gut SynCom (20HM) via the following objectives: (1) Establish the requisite conditions for a robust and reproducible continuous culturing platform using a representative SynCom, coupling this to sequencing and informatics analysis to develop a rapid community composition monitoring system; (2) Leverage this continuous system to obtain insights into community dynamics via strain competition and introduction of a methanoarchaeon; (3) Assess the impact on an established community of temperature fluctuation and introduction of a lytic virus. Real-time community monitoring will be used to guide the selection of samples for further analysis. Metatranscriptomics will be used to understand gene expression in response to abiotic or biotic stresses and metagenomics to monitor the impact of the virus at a genomics level. We will use these data to develop mechanistic models for understanding community dynamics. Overall our project aims to move beyond purely descriptive and correlative toward more causal studies and will address three highlighted challenges in the area of integrative microbiome research: understanding variation in microbiome composition, the impact of disturbance, and the functional properties of the microbiome. Leveraging our collaborative networks, we will test the applicability of this system to plant biomes to help acquire insights into the mechanisms behind how microbial communities influence plant health in the future.

• DFG Programme: Research Grants
• International Connection: United Kingdom
• Cooperation Partner: Professor Rob Finn