Our research is focused on elucidating the structure and functions of the ribosome, understanding the basic principles of protein synthesis in bacteria, the modes of action of ribosome-targeting antibiotics, and mechanisms of drug resistance at a structural level. While the general process of protein synthesis is relatively well understood, several fundamental questions central to the ribosome structure, function and evolution remain obscure. Understanding these aspects of translation is greatly facilitated by the use of X-ray crystallography technique that provides a structural basis for the molecular mechanisms, by which the ribosome and associated translation factors (such as release factors) achieve their roles in protein synthesis. We use cutting-edge X-ray crystallography technique to determine atomic-resolution structures of the bacterial ribosome in functional complexes with various translation factors and ribosome-targeting antibiotics. Our structures provide the basis for the understanding of how different elements of ribosome function together at the molecular level. Importantly, using the functionally relevant ribosome complexes, such as those that contain natural tRNA substrates, we produce principally new data, highly relevant to the actual mechanism of action of an antibiotic or a translation factor.
Our new laboratory was established in 2015 when I joined the team of faculty at the Department of Biological Sciences jointly with the Department of Medicinal Chemistry and Pharmacognosy at the University of Illinois at Chicago (UIC). As an independent laboratory, we have already published several experimental papers, in which we have unraveled the mechanisms of action of several new antibiotics and revised the modes of action of a number of the old drugs. We found that structural models showing how various translation factors and antibiotics interact with vacant bacterial ribosomes can provide information that is incomplete or possibly even misleading, which is because the critical interactions of a factor/antibiotic and the ribosome critically depend on the presence of natural ribosomal ligands, such as mRNA and tRNAs. We started to routinely use ribosome complexes containing natural tRNAs that fortuitously led us to a significantly higher resolution of our electron density maps due to the stabilization provided by the ribosome-bound tRNA molecules. We believe that only the high-resolution structures of various translation factors bound to the functionally meaningful complexes of the ribosome can supply information essential for understanding the actual mechanisms of their action. In the course of our studies, we have generated resources and techniques, which are in high demand in other research laboratories in academia and the pharmaceutical industry.
Our new laboratory was established in 2015 when I joined the team of faculty at the Department of Biological Sciences jointly with the Department of Medicinal Chemistry and Pharmacognosy at the University of Illinois at Chicago (UIC). As an independent laboratory, we have already published several experimental papers, in which we have unraveled the mechanisms of action of several new antibiotics and revised the modes of action of a number of the old drugs. We found that structural models showing how various translation factors and antibiotics interact with vacant bacterial ribosomes can provide information that is incomplete or possibly even misleading, which is because the critical interactions of a factor/antibiotic and the ribosome critically depend on the presence of natural ribosomal ligands, such as mRNA and tRNAs. We started to routinely use ribosome complexes containing natural tRNAs that fortuitously led us to a significantly higher resolution of our electron density maps due to the stabilization provided by the ribosome-bound tRNA molecules. We believe that only the high-resolution structures of various translation factors bound to the functionally meaningful complexes of the ribosome can supply information essential for understanding the actual mechanisms of their action. In the course of our studies, we have generated resources and techniques, which are in high demand in other research laboratories in academia and the pharmaceutical industry.