Special Biochemistry Seminar - Israel Fernández

CRISPR systems evolved in Bacteria and Archaea as defense mechanisms against Mobile Genetic Elements (MGE) such as viruses. The diversity of CRISPR systems as well as their prevalence among prokaryotic species suggest a scenario of rampant conflict between cells and MGE at the microbiology domain. With conflicts of such wingspan, arms-races at the molecular level are common, with shuffling of genes and/or gene exaptation events providing defense/attack systems with novel strategies to overcome adversarial situations. Using cryoEM, we studied in detail a bacterial transposon that exapted the DNA binding machinery of a CRISPR system for precise DNA location, binding and mobilization. Driven by accurate base pairing specified by the RNA component of the CRISPR system, these transposons are able to mobilize large DNA cargo molecules ranging in size from 0.5 to 5 kilo-bases to distant locations in bacterial genomes. We will focus our discussion on technical aspects of cryoEM, describing the problems we faced in the characterization of this system in order to attain high-resolution regimens. Additionally, we will discuss two new problematic samples for cryoEM we are working with that exemplify our approach to hard cryoEM targets.

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Dr. Israel S. Fernandez is an expert in cryo-EM based structural biology of protein-RNA complexes. While at the laboratory of the Nobel laureate Dr. Venki Ramakrishna at the LMB-MRC in Cambridge, Dr. Fernandez pioneered the elucidation of high-resolution cryo-EM structures of complete ribosomes that resulted in several seminal publications. As a group leader at Columbia University and St. Jude Children's Research Hospital in the US he has continued to make important contributions to understand the structural basis of RNA biology, from ribosomes to CRISPR/Cas. At the IBF he has stablished a research group focused on elucidating the ribosome contribution to the genomic expansion of retrotransposons in the human genome.