Chemical Society Seminar: Dr. Joaquin Ortega - The Impact of Recent Improvements in Cryo-electron Microscopy Technology on the Understanding New Antimicrobial Targets

Multidrug resistance infections are putting us at risk of entering into a ‘postantibiotic era’ with people at the mercy of microbes and treatments like major surgery no longer possible. New approaches and significant efforts must be focused on developing new antibiotics. Our research aims to understand the structure and function of new antimicrobial targets, developing them into tangible enzymes for intervention with new antibiotics. Current work focuses on the assembly process of the ribosome; a pathway of tremendous potential but that has not been explored as a target for antimicrobials yet. Cryo-electron microscopy (cryo-EM) had played a central role in the study of ribosome structure since the  development of this technique in the mid 1980s. Until recently cryo-EM structures were limited to ~10Å in the best cases. However, the recent
advent of direct electron detectors has greatly improved the resolution of cryo-EM structures to the point where atomic resolution is now achievable. This improved resolution is allowing cryo-EM to make groundbreaking contributions in essential aspects of ribosome biology, including the assembly process. In my talk, I will summarize important insights that cryo-EM, in combination with chemical and genetic approaches, has already brought to our current understanding of the ribosomal assembly process in bacteria using previous detector technology.
More importantly, I will discuss how the higher resolution structures now attainable with direct electron detectors can be leveraged to propose precise testable models regarding this process. These structures are providing an effective platform to develop new antibiotics that target this fundamental cellular process.