The structural dynamics of ribosomal frameshifting and ribosome rescue

PUBLIC HEALTH RELEVANCE STATEMENT (PROJECT NARRATIVE) This proposal aims to elucidate how the process through which the ribosome, the universally distributed biological machine that synthesizes all of the proteins encoded in an organism’s genome, synthesizes proteins is controlled at a level of detail much higher than is currently available. Because the bacterial ribosome is the molecular target of over half of the small-molecule antibiotics that are in current clinical use, the results of the proposed studies are expected to identify new targets and strategies for the development of next-generation antibiotics. Similarly, because aberrant control over the process through which the human ribosome synthesizes proteins plays a causal role in several human diseases, including numerous viral infections and cancers, the results of the proposed studies are expected to inform the development of small-molecule therapeutics that can be used to treat viral infections, cancers, and other human diseases.