Translational Attenuation on the Ribosome
Ribosomes are essential catalytic machines in all living organisms that translate genetic information into protein via amino acid polymerization. Many antibiotics and proteins bind to the ribosome and impair its function by inhibiting translation or by interfering with proper ribosome biogenesis. One of the focuses in the lab is to investigate how ribosome-targeting antibiotics arrest translation by impeding ribosome movement on its template mRNA during elongation (“ribosome stalling”), and how pathogenic bacteria exploit the ribosome stalling mechanism to acquire antibiotic resistance. Our recent global translatome analyses show that the widely prescribed ribosomal antibiotic preferentially inhibits translation of specific protein targets in a sequence-dependent manner that results in the evasion of translational inhibition of other “resistant” proteins. The second focus of the lab is to explore the multifaceted roles of ribosome inactivating factors in maintaining ribosome integrity and in modulating translational activity during bacterial stress adaptation. Our work is based on integrating genetics, biochemical, and genome-wide approaches to study fundamental aspects of translational control in Staphylococcus aureus.