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CRISPR-Cas Systems: From Humble Beginnings to Today’s Headlines
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CRISPR-Cas Systems: From Humble Beginnings to Today’s Headlines

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JHE 264

Prof. Sylvain Moineau PhD is the Canada Research Chair in Bacteriophages. He is from the Department of Biochemistry, Microbiology and Bioinformatics in the Faculty of Sciences and Engineering from Université Laval, Quebec city, Quebec, Canada.


Viruses are now recognized at the most abundant biological entities on the planet and display a remarkable genetic diversity. Not surprisingly, bacteria have a plethora of diverse defense mechanisms to combat their phages. Four decades after the discovery of one such defense mechanism, restriction enzymes, another bacterial anti-phage system that cleaves foreign DNA was identified—one that acts as an adaptive immune system. Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated cas genes protect microbial cells against infection by foreign nucleic acids, including phage genomes and plasmids. Bacterial CRISPR-Cas type II systems function by first incorporating short DNA ‘spacers’, derived from invading phage genomes or plasmid sequences, into a CRISPR array located in their genome. This step is known as adaptation or vaccination. The CRISPR array is then transcribed and matured into short RNAs (the maturation step), which, by recruiting a Cas endonuclease, act as surveillance complexes that recognize and cleave invading matching sequences (the interference step). The cleavage occurs near a short motif, called the PAM, adjacent to the sequence targeted by the spacer. Phages can bypass the protection provided by CRISPR-Cas through point mutations, deletions, or the production of anti-CRISPR proteins. Exploiting this system has also resulted in the development of the much-publicized CRISPR-Cas9 technology for precise genome manipulation of various organisms. This seminar will mostly recall the roles played by phages in the discovery and understanding of CRISPR-Cas systems. Finally, I will highlight the use of CRISPR-Cas9 technology for viral genome editing in order to better understand phage-host interactions.