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Areas of interest: New antimicrobial targets. Mechanisms of ribosome assembly.

Ribosomes are responsible for the process of decoding mRNA into proteins, a process essential to sustain life. Bacteria with defects in ribosome biogenesis exhibit slower growth and severely reduced ability to cause disease. Ribosomes are comprised of a small (30S) and a large (50S) subunit and overall they contain over 50 different components. In recent years, extraordinary efforts in structural biology have provided atomic structures of the ribosome generating a detailed three-dimensional view of the process of protein synthesis and how antibiotics currently used in the clinic function by targeting the mature ribosome. These structures have been essential to both find new antibiotics as well as to make existing ones more powerful. However, atomic resolution structures of ribosome assembly intermediates have not been obtained and the present structural understanding of the intricate process of assembly of the ribosome is very superficial. This void of knowledge limits our ability to develop new antibiotics targeting the process of ribosome assembly. The Ortega lab uses cryo-EM to obtain atomic resolution structures of ribosome assembly intermediates and visualize in 3D the complexity of this process. Structural biology techniques have been instrumental in the discovery of antibiotics targeting the mature ribosome. The atomic resolution structures of immature ribosomes obtained in our laboratory are having the same impact and are providing an extensive reservoir for the discovery of new antibiotics that target ribosome assembly.