Characterization of lectins to understand human microbiome functions and develop live biotherapeutics

Project Summary Almost all living cells use specific non-enzymatic carbohydrate binding proteins (e.g. lectins) to recognize carbohydrate ligands for cellular trafficking, signaling and defense. The systematic study of lectins and their carbohydrate ligands has improved our understanding of human health and the high specificity of lectins for certain cellular interactions has made them a valuable resource for therapeutic discovery. In previous research, my laboratory suggested that human commensal microbiota utilize lectins (e.g. human-microbial-lectins) to regulate a complex network of host-microbe interactions beyond those mediated by simple pattern recognition receptors and conserved microbial metabolites. Furthermore, our characterization of a highly prevalent human- microbial-lectin Cbeg5 suggests this specific lectin may regulate fundamental human myeloid cell interactions integral to normal microbiome homeostasis. As such, the central hypothesis of this proposal is that the study of Cbeg5 and other human-microbial-lectins will elucidate microbiome functions relevant to human health and which can be developed therapeutically. We will advance this hypothesis through three aims to define (1) how Cbeg5 regulates distinct myeloid cell populations, (2) the potential to develop Cbeg5 as a therapeutic for inflammatory bowel disease, and (3) to explore the larger network of microbiome interactions regulated by human-microbial lectins.