Most bacteria live in organized multicellular communities called biofilms. Biofilms have been linked to a variety of problems important to humans: biofilms contaminate water supplies, medical equipment, and industrial machinery, and biofilms cause many persistent infections. A fundamental goal in microbiology is to understand how these interesting and important bacterial communities develop. Recently, it has become apparent that bacteria use a number of conserved design principles to build a biofilm. Namely, cells produce extracellular signals to communicate information about cell density and cell position and this information is used to regulate the temporal and spatial expression of developmental genes. This project focuses on the regulation of developmental genes in Myxococcus xanthus. When starving, M. xanthus forms a biofilm containing a thin mat of cells and multicellular fruiting body structures. A cascade of enhancer binding proteins (EBPs), which is designed to respond to a variety of extracellular signals, is used to regulate many developmental genes. The long-term goal of this project is to understand how this regulatory network coordinates developmental gene expression and, ultimately, how it promotes the assembly of a biofim. The EBP Nla4 functions at the front end of the cascade, regulating the entry into development. The aim of this project is to understand how Nla4 helps cells navigate through this critical juncture in development. Specifically, this project aims to find Nla4 target genes, to understand how Nla4 recognizes target promoters and to determine whether these target genes are important for development. It seems likely that regulatory networks analogous to the EBP cascade will be a common theme in bacteria that make biofilms, since they must also process a variety of signal information to properly regulate their developmental genes. Therefore, we believe that this project will lead to a model for gene regulation that is pertinent to many bacterial systems.
Bacterial development yields a remarkable array of complex multicellular forms. Arguably, one of the most interesting and important forms of bacterial multicellularity is a surface-associated aggregate of cells known as a biofilm. Mature biofilms are complex and often contain highly ordered structural features such as towers of cells. Furthermore, biofilms are highly resistant to toxic chemicals such as those found in household cleaners, to chlorine, which is often used to treat water, and to many of the antibiotics commonly used to treat human infections. A fundamental goal of microbiology is to better understand how biofilm formation begins, since biofilms are difficult to eradicate once they have formed. The overall aim of this project is to identify genes that trigger biofilm formation in a model bacterial system. This project has uncovered new classes of genes that are important for the initiation and early stages of biofilm formation. These genes are now be analyzed in more detail to determine their specific functions. This project has contributed to the scientific training of four graduate students, eight undergraduate students and one high school student. This project has also been used as a platform to discuss careers in science with local high school students and undergraduate students who are from underrepresented groups.
