Translational Control: Discovery and Mechanisms

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Project Summary/Abstract Ribosomes are at the center of gene expression regulation. Not only do they synthesize proteins, but they regulate transcription and respond to stress signals. The translational control underlies the pathogenesis of infectious and genetic diseases. Translation is a key antibiotic target, but the emergence of antibiotic resistance poses a serious challenge in the fight against infectious diseases. To improve our understanding of the translational control of gene expression in molecular detail, we propose to elucidate the structural mechanisms of (1) translation initiation of viral mRNAs and virus-like cellular mRNAs; (2) bacterial stress responses which couple translation with transcription, conferring bacterial pathogenicity and antibiotic resistance and (3) translation elongation and termination. Understanding these mechanisms may enable discovery of novel drugs for the treatment of viral or bacterial infections or genetic diseases caused by nonsense mutations.