Cyclic Dimeric GMP, A Novel Second Messenger in Bacteria: Molecular Mechanisms

University Of Wyoming, Laramie WY

Investigators

Abstract

Cyclic dimeric guanosine monophosphate, c-di-GMP, identified in the 1980s as an allosteric activator of the bacterial cellulose synthase, has emerged in the last few years as a ubiquitous second messenger in Bacteria. C-di-GMP affects exopolysaccharide synthesis, biofilm formation and structure, flagella- and pili-based motility as well as gene expression. This makes c-di-GMP an important regulator of the transition from the motile, single-cellular lifestyle to a sessile, multicellular (biofilm) lifestyle. In addition, c-di-GMP affects symbiotic and parasitic interactions of bacteria with animals and plants. Considering the scope of its effects on bacterial physiology and behavior, c-di-GMP appears to be at least as important as the better-known cyclic nucleotide second messenger, cAMP. Therefore, understanding how c-di-GMP operates is of fundamental importance in bacteriology. However, with the exception of bacterial cellulose synthases, the identities of c-di-GMP receptors, end-targets and mechanisms of action remain essentially unknown. The objective of this project is to elucidate molecular mechanisms through which c-di-GMP operates, using bacterium Escherichia coli as a model. To achieve this objective the PI's lab will identify and characterize c-di-GMP receptors and end-targets in this bacterium. The PI also intends to uncover mechanisms by which c-di-GMP affects gene expression in E. coli. These advances will ultimately result in the comprehensive picture of c-di-GMP-mediated signal transduction in a model organism. Society in general may benefit significantly from this project because the knowledge obtained here will provide important insights into bacterial physiology and behavior, which will allow manipulation of various bacteria of medical, agricultural, and biotechnological significance. This project will provide interdisciplinary training opportunites (in bioinformatics, bacterial genetics, protein-ligand biochemistry, physiology, transcriptomics and proteomics) to the graduate student(s) and postdoctoral fellow(s) involved. Research experiences will be provided to undergraduate students and to minority high school students enrolled in the Summer Research Apprenticeship Program. A key microarray experiment will be carried out by undergraduate students enrolled in the lab course taught by the PI and will be supervised primarily by a highly qualified postdoctoral fellow supported by this project. This will allow students to address a real-life research problem using modern (and expensive) approaches, which otherwise would be inaccessible to them. The graduate student(s) and postdoctoral fellow(s) involved in this project will give lectures on c-di-GMP in the Microbial Physiology and Metabolism course taught by PI. Results of this project will be presented at scientific meetings and articles will be published in peer-reviewed journal(s).