Seminars

Physical (protein-protein) and functional (gene-gene, or genetic) interactions define the molecular organization of the cell. While proteomics approaches can identify physical interactions between proteins they do not necessarily reveal pathway-level relationships. On the other hand, genetic screens, where the growth of a double mutant is compared to a no-interaction model based on the fitness of the corresponding single mutants, can elucidate the functional relationships between genes. High-throughput experimental systems to examine genetic interactions on a genome-scale in eukaryotes have been successful in delineating epistatic relationships but have been limited in prokaryotes. I will present how our recently developed high-throughput genetic screening approach in the model prokaryote, Escherichia coli, is being exploited in a global screening effort to infer functional relationships and redundancy in conserved, clinically-relevant, core biological processes such as cell envelope and protein synthesis that mediate bacterial functions, fitness, proliferation, adaptation, and genome integrity. Characterization of such conserved networks is critical for uncovering targets for antimicrobial discoveries.