In order to grow and survive in variable and often hostile environments, bacteria have evolved amazing adaptation mechanisms. These include complex stress responses and the formation of multicellular aggregates, i.e. biofilms, which cause serious biomedical and technological problems. Research in the Hengge group focusses on the genetic mechanisms and complex control networks that underly biofilm formation in the model organism Escherichia coli, which includes commensals as well as important pathogens. Special emphasis lies on the role of signaling by the ubiquitous bacterial second messenger cyclic-di-GMP, which is produced and degraded by diguanylate cyclases (carrying GGDEF domains) and specific phosphodiesterases (with EAL domains), respectively. The goal is to elucidate the regulation, function, cooperation and targets of the 29 GGDEF/EAL domain proteins of E. coli and their c-di-GMP-binding effector components during the entire series of molecular events that generates a biofilm. As cyclic-di-GMP is used by most bacteria, understanding its production and mode of action will open new and general perspectives for interference with bacterial biofilm formation.