Besides known adhesins, more proteins with unknown function and a validated role in colorectal cancer development were identified in commensals. The underlying mechanisms are entirely unknown, i.e. if the proteins mediate cell or extracellular matrix adhesion or activate a signaling pathway, such as Wnt/b-catenin or TLR signaling. Therefore, we apply genomic screenings (e.g. CRISPR-Cas9) and biochemical screening methods to identify the cellular receptors of these proteins with unknown function.
After confirming protein-protein interactions between CRC-driving commensal factors and human epithelial receptors, we will determine the complex structures to understand the underlying molecular mechanisms and facilitate drug development.