In recent years it has become apparent that many, if not most bacteria live in organized multicellular communities called biofilms. Biofilms have been linked to a variety of problems that are important to humans: they contaminate water supplies and industrial machinery, and they cause many persistent infections in plants and animals. A fundamental goal of researches that study biofilm formation and other model systems for multicellular development in bacteria is to understand how programmed changes in gene transcription guide the formation and maintenance of bacterial communities. Fruiting body formation in M. xanthus is the best characterized model for the genesis of the highly ordered structures that are important components of most biofilms. Previous work has shown that NtrC-like activators play prominent roles in regulating changes in gene transcription during the development of multicellular fruiting bodies. This project focuses on two of these NtrClike activator proteins, Nla6 and Nla28. The long-term goals of this project are to determine how these NtrC-like proteins identify their target developmental genes and to define the roles that Nla6 and Nla28 target genes play in fruiting body development. These studies will help test the hypothesis that M. xanthus coordinates changes in developmental gene transcription by using a series of NtrC-like activators to turn on specific sets of genes at specific stages of fruiting body formation. On a broader scale, these studies will provide important information about the intimate relationship between changes in gene transcription and the formation and maintenance of bacterial communities such as those found in biofilms. This project will serve to train graduate and post doctoral students.