Yale Goldman

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Single Molecule Dynamics of mRNA Translation

Ribosome catalyzed protein synthesis is a core function of all living cells, but how it proceeds differs in detail between bacterial cells and eukaryotic, including mammalian, cells. These differ- ences are exploited in frequently utilized antibiotics, such as neomycin and erythromycin, which specifically target the bacterial ribosome and combat bacterial infections. However, widespread resistance to ribosomal antibiotics has limited their use. We are proposing sophisticated bio- chemical and biophysical studies to determine the precise functioning of bacterial ribosomes and how the rate and amount of expression is controlled by native and pathogen genomes. The knowledge gained from our experiments should both advance our basic understanding of how cells function and facilitate the development of new antibiotics for human use. Mechanisms re- vealed in the bacterial ribosome may either apply directly to eukaryotic protein synthesis or else help to inform further studies of the protein synthesis machinery of higher organisms. Specific mechanisms that are required for replication of viruses, such as programmed frameshifting, may someday be targets of therapy against cancer or AIDS.