Our research focuses on uncovering the structure and function of the ribosome, with a particular emphasis on understanding protein synthesis in bacteria, the mechanisms of action of ribosome-targeting antibiotics, and drug resistance at the structural level. While the general process of protein synthesis is well understood, several fundamental questions central to the ribosome structure, function, and evolution remain unanswered. We address these questions using advanced X-ray crystallography and cryo-electron microscopy (cryo-EM) to obtain atomic-resolution structures of bacterial ribosomes in functional complexes with translation factors and antibiotics.

Our work provides detailed insights into how different ribosomal elements work together at the molecular level. By studying ribosome complexes that include natural tRNA substrates, we generate principally new data that reveal the true mechanisms by which antibiotics and translation factors act. Our findings also highlight that studying vacant ribosomes or incomplete complexes can lead to misleading conclusions, as critical interactions between antibiotics or factors and the ribosome depend on the presence of natural ribosomal ligands like mRNA and tRNAs. These functionally relevant ribosome complexes not only offer more accurate insights but also improve structural resolution due to the stabilization provided by ribosome-bound tRNAs.

Since our lab was established in 2015, we have published several key papers that unraveled the mechanisms of action of new antibiotics and revised the understanding of some older drugs. Our research aims to achieve a deeper understanding of how the ribosome functions, how antibiotics inhibit it, and how resistance mechanisms develop to overcome drug action. This knowledge will inform the future design of antibiotics that more effectively kill pathogenic bacteria and may offer new strategies for modulating protein synthesis, providing potential therapeutic avenues for various human diseases.