Establish new model species for the human gut microbiome

An important aspect of understanding microbiomes is increasing our knowledge of their composition – from viruses to bacteria to single-celled eukaryotes – and the functions they encode. For example, there are thousands of bacterial species that have been identified in the human gut microbiota from metagenomics datasets, yet most of these species are still terra incognita in terms of the functions they encode. Moreover, the available model organisms like E. coli are not suitable for studying the microbes that colonise the human gut because they are neither the most prevalent nor the most abundant bacteria in the gut microbiome. The Flagship project aims to focus on two bacterial species that are abundant in the human gut but remain poorly characterised: Phocaeicola vulgatus and Bacteroides uniformis. This aim is to use pioneering ways to molecularly characterise these species and to understand the underlying molecular mechanisms of microbiome–host–environment interactions.

Among the participating teams of the flagship project: Typas group is pioneering tools for pooled and arrayed transposon mutant libraries in these species to define gene essentiality and function – with a focus on functions these bacteria use to engraft in communties. The Savitski group is employing a suite of proteomic methods, such as multiplexed Thermal Proteome Profiling, to construct a detailed protein-protein and protein-ligand interaction landscape in these organisms. The Zimmermann-Kogadeeva group is integrating computational and experimental techniques to elucidate metabolic network architecture, and in collaboration with Alex Westermann from HIRI, aims to characterise transcriptional regulation in both species. Michael Zimmermann’s group, along with the groups of Nassos Typas, Georg Zeller, Peer Bork, Rob Finn and John Lees, are functionally characterising the genetic and phenotypic intra-species diversity – specifically related to xeno-metabolism. Finally, the Finn group is developing a portable prokaryotic annotation pipeline to integrate data generated from the Flagship project.

Together, this project will elucidate the functional roles of numerous unknown genes, proteins, and metabolites in two key species, ultimately enhancing our ability to understand, protect, and beneficially manipulate the gut microbiome.

Understanding the factors underlying the predominance of Prevotella species in the gut microbiome of individuals consuming non-Western diets

Caroline Tawk is a Postdoctoral fellow in the Microbial Immune Regulation group led by Till Strowig (HZI). In collaboration with the Typas’ group (EMBL Heidelberg) – she aims to uncover what makes Prevotellaceae species so prevalent in the gut of non-westernised societies.

The main goals of the project are: to establish if there is a direct competition between Prevotellaceae and Bacteroidaceae species in the gut; to find the causes underlying a Prevotellaceae-dominated microbiome in non-western societies and to determine if Prevotellaceae dominance is beneficial for health.

Joachim Hug is a Postdoctoral fellow in Typas’ group (EMBL Heidelberg), working in collaboration with the Zeller’s group (EMBL Heidelberg-LUMC) and Strowig’s group (HZI). His project combines state-of-the-art bioinformatic approaches, high-throughput genetics and phenotypical co-cultivation screening to characterise the metabolic and biosynthetic capability of the Bacteroidota phylum. 

The main goal of this project is to discover and characterise new groups of Bacteriocins and other secondary metabolites with a focus on ribosomally synthesized and post-translationally modified peptides (RiPPs) with therapeutic potential.

Shafaque Rahman is a Postdoctoral fellow in J. Hühn’s group (HZI). In collaboration with the Zimmermann’s group (EMBL Heidelberg), her project focuses on identifying the microbiota-derived metabolites that modulate the numbers and the functional properties of tissue-resident regulatory T cells.

The main goal of this project is to find the molecular mechanisms underlying canonical and non-canonical microbiota-controlled functions of tissue-resident regulatory T cells in humans.