Cyanobacteria are often associated with microbial assemblages called biofilms that can cause fouling of industrial surfaces, but can also be beneficial, e.g., in water purification processes. Despite the environmental prevalence and economic consequences of cyanobacterial biofilms, the molecular mechanisms that underlie the formation of these structures have received little attention. The current proposal uses molecular genetics and sophisticated molecular and chemical techniques to understand the regulation of biofilm formation in the model cyanobacterium Synechococcus elongatus. Recent data suggest that the project will characterize a secreted inhibitor of biofilm formation, identify mechanisms of sensing the inhibitor, and determine the pathways for producing a biofilm in S. elongatus. Understanding this natural biofilm-inhibition system will be useful in designing strategies to minimize damage from detrimental biofilms and to elicit the formation of beneficial cyanobacterial biofilms. The project will train students from US and Israeli labs in microbiology, deep sequencing, and cutting-edge imaging technologies. The project will generate genetic tools and strains that will be made available to the research community, and any useful intellectual property that emerges from the work will be disclosed for commercialization. As part of the ICOB program it will also establish international research collaborations with Israel.