We thrive to understand the molecular mechanism underlying the interaction of the intestinal microbiome with the human host. We focus on bacteria that are overrepresented in the microbiome of colorectal cancer (CRC) patients and the interactions of bacterial adhesins with epithelial and immune cells of the intestinal system. Genomic sequencing, big data analysis, and substantial microbial studies in animal models identified important drivers of CRC on the microbial and cellular level, but the underlying mechanistic details are not known. Therefore, we structurally analyze complexes between commensal proteins and human receptors to understand the molecular background of their binding mechanisms.
We apply cryogenic electron microscopy (Cryo-EM) and single particle analysis to determine the structures of protein complexes that facilitate the host-microbiome interaction, which is a prerequisite for structure-based design of personalized anticancer compounds. In addition, we visualize molecular details of bacteria interacting with the host epithel via cryo-ET to understand their binding mechanisms in a cellular context. Finally, we attempt to identify yet undescribed bacterial adhesins that facilitate epithelial binding in a pathogenic context using genomic and biochemical screening systems.
Research SectionStructural Biology