סמינר לפיזיקה של מערכות ביולוגיות וחומרים רכים: The combinatorial logic of the BMP signaling pathway
Dr. Yaron Antebi, Weizmann institute of sciences
Cell-cell communication systems are inherently combinatorial, as multiple ligands and receptor variants function together to control cellular behavior. The complex way in which cells integrate these signals still remains poorly understood. In this talk we will focus on ligand integration within the Bone Morphogenetic Protein (BMP) pathway, a key developmental signaling pathway, and uncover the combinatorial logic of such systems. By systematically measuring the cellular response to multiple BMP ligands we can classify ligands into equivalence groups based on their profile of positive and negative synergies with other ligands. Using this classification we generate ligand interaction maps that encode efficiently the combinatorial logic of the BMP pathway. We find that these maps vary, in specific patterns, with receptor expression. This provides a quantitative framework to analyze context dependent effects of ligands across biological processes. Finally, using a biochemical model based on competitive formation of signaling complexes we gain intuitive insights into the mechanism governing the combinatorial logic. Together, these results reveal the roles of BMP combinations in developmental and therapeutic contexts and establish a framework for analyzing other combinatorial, context-dependent signaling systems.