SPP 2474:  Illuminating gene functions in the human gut microbiome

• Subject Area: Medicine ; Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 540841827

The DFG Priority Program SPP 2474 is dedicated to uncovering gene functions in prevalent and abundant commensal members of the human gut microbiome. The goal is to discover new biological pathways, protein complexes, metabolites, and molecular mechanisms in these understudied microbes, which play a crucial role in human health. This task is being tackled using new systems-level technologies that overcome the major challenges of studying the large variety of non-model bacteria in the gut microbiome. A key challenge in this program is to bring together experts in molecular biology, technology development, and microbiology in an interdisciplinary consortium. To achieve this, a well-organized and strategic coordination framework is essential. This framework will ensure that the program's success goes beyond the results of individual projects, fostering strong collaboration and maximizing collective impact. To support this mission, we propose a range of tailored measures. These include appointing a coordinator assistant and providing further scientific administration support to the spokesperson, as well as network funds for SPP-specific biomaterials and data management. To help young scientists develop their skills and career, this SPP is dedicated to offer an ideal environment for them, including wet- and dry-lab workshops on relevant topics, training grants to access the EMBL Microbial Automation and Culturomics Core Facility, and start-up funding to help early-career researchers reach early independence. Additionally, we will implement strategies to ensure an inclusive, gender-balanced, and family-friendly research environment, going beyond the standard support provided by participating universities and institutes. For effective internal and external communication—critical for successful collaboration and dissemination of our work —we request funding for annual meetings, an international conference, a website, and social media outreach. We also plan public outreach activities to engage a broader audience, as microbiome research is a topic of widespread interest. In conclusion, we are convinced that the proposed measures will provide the framework needed for the success of this SPP. If successful, this initiative will establish new international standards in functional microbiome science and produce valuable knowledge, technologies, and resources that will benefit the field for decades.

• DFG Programme: Priority Programmes
• International Connection: Portugal, United Kingdom

Projects

• A data hub for the functional annotation and exploration of genomes from the human microbiome (Applicant Finn, Rob )
• AI-based identification and functional characterization of human gut microbiome-derived natural products (Applicants Helfrich, Eric Jan Nikolaus ;  Müller, Volker )
• Coordination Funds (Applicant Maier, Lisa )
• Deciphering the molecular mechanisms of inter-species bacterial communication in the gut microbiome (Applicant Papenfort, Kai )
• Elucidate the evolution and function of genes driving Bifidobacterium colonisation in the infant gut (Applicant Key, Felix Michael )
• Elucidating cell-surface protein complexes and their assembly in Bacteroidota (Applicants Mahamid, Ph.D., Julia ;  Savitski, Ph.D., Mikhail ;  Selkrig, Joel )
• Elucidating mechanisms of metabolic interaction and gene function in spatially interacting microbiome keystone bacteria (Applicants Ralser, Markus ;  Stecher-Letsch, Barbara )
• Exploring the dark matter of microbial metabolic interactions and its relevance for bacterial metabolism in a simplified model gut microbiome (Applicants von Bergen, Martin ;  Kaleta, Christoph )
• Functional adaptation of Phocaeicola vulgatus in response to metabolic injury and chronic inflammation (Applicants Haller, Dirk ;  Schirmer, Melanie )
• Functional characterization of Bacteroidota RRM proteins: a prevalent family of RNA-binding proteins in the human gut microbiota (Applicant Westermann, Ph.D., Alexander )
• Genetic and molecular determinants of specialized metabolite functions mediating gut microbial interactions in Fusobacterium nucleatum (Applicants Faber, Franziska ;  Hertweck, Christian ;  Vogel, Jörg )
• Genetic drivers of the spatial ecology around dietary substrates (Applicant Jahn, Martin Thomas )
• Genomic and functional diversity of cholesterol metabolism by human gut microbes (Applicant Poyet, Mathilde )
• How a commensal bacterium of the genus Desulfovibrio finds its niche in the gut and how this process can be stopped (Applicant Jung, Kirsten )
• How Segatella copri deals with oxygen: Mechanisms for the conversion of O2 and peroxides in an obligate anaerobic gut bacterium (Applicants Fritz-Steuber, Julia ;  Seifert, Jana )
• Molecular characterization of inter-species cross-feeding within the human gut microbiome (Applicant Strowig, Till )
• Projekt Z01 – Bereitstellung zentraler Ressourcen und Informationen für das humane Mikrobiom (Applicants Clavel, Thomas ;  Overmann, Jörg )
• The Bacteroides type VI secretion systems as unique machineries for the transmembrane transport of effector proteins with unknown function (Applicants Sondermann, Ph.D., Holger ;  Unterweger, Daniel )
• UNCODE - Uncovering New Clostridial Gene Functions Using Off-Target Drug Effects on Human Gut Microbes (Applicants Maier, Lisa ;  Sieber, Stephan A. )
• Understanding the role of molecular and cellular structures in gut acetogens as key adaptive strategies for survival in a competitive microbiome. (Applicant Schuller, Jan Michael )
• Unlocking the functional potential of specialized metabolites in Eubacteriales from the human gut (Applicants Clavel, Thomas ;  Gulder, Tobias A. M. )
• Unraveling the arsenal and mechanisms that Bacteroidetes use for kin competition (Applicant Typas, Ph.D., Athanasios )

• Spokesperson: Professorin Dr. Lisa Maier