Project Details
Projekt
Phage-host cross-talk in the human gut microbiome
Applicant
Professorin Dr. Li Deng
Subject Area
Microbial Ecology and Applied Microbiology
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 464797012
Gut dysbacterioses, or imbalance in gut bacteria, are increasingly found to be associated with − and possibly cause for − a wide range of diseases, including inflammatory bowel disease (IBD) and graft-versus-host disease (GVHD). Phages regulate bacterial abundance, diversity, and metabolisms in numerous ecosystems. While their role in the gut remains largely unexplored, it has been suggested that they may play a similar role in the human gut. In Phase I, we developed experimental and analytical tools to study phage-bacterial interactions in gastrointestinal diseases. We identified links between these interactions and IBD and GVHD by identifying Auxiliary metabolic genes (AMGs) that maintain gut homeostasis such as immunomodulatory metabolites (IMMs). Our chief aim in Phase II is to to reveal the molecular mechanisms underlying bacterial metabolic reprogramming caused by vIMM-encoding phages and their knock-on effect on the gut microbiome. Our objective I is to create a comprehensive database of vIMM and phage genomes. We will expand our dataset using a bioinformatics pipeline established in phase I to identify new AMGs in IMM generation. We will annotate vIMM-carrying phage genomes using Pharokka and compare their predicted structures with the AlphaFold Database and RCSB Protein Data Bank. We will create a public database of all vIMM-carrying phage genomes to help discover new vIMMs associated with human diseases. Our objective II is to isolate and characterize vIMM-carrying phages and their bacterial hosts systematically and to reveal the molecular mechanisms behind the bacterial metabolism reprogramming that is caused by these phages. We will use a targeted isolation approach called POSH and anaerobic culturomics to isolate phages and their host bacteria from our IBD cohorts. Objective III is to gain a mechanistic understanding of vIMM phage-mediated bacterial modulation in the broader GI ecosystem. We will use the Robogut, a bioreactor ex vivo model designed to mimic the physiological conditions of the human GI tract and to study the interactions between vIMM phages and GI bacteria.
DFG Programme
Priority Programmes
