CRISPR-Cas Immune System: Molecules, Mechanisms and Microbes

Abstract

The ongoing evolutionary arms race between bacteria and their predatory phages gives rise to the evolution of different anti-phage defense systems. Among these, CRISPR-Cas represents an RNA-mediated adaptive and heritable immune system that protects the bacteria and archaea against the invasion of mobile genetic elements such as phages and plasmids. Exploitation of this immune system gave rise to a widely acclaimed and versatile genome editing technology referred as CRISPR/Cas9 and several variants thereof. In this talk, I will emphasize the centrality of RNA in orchestrating the defense response. The defense mechanism proceeds via three distinct stages: (i) acquisition of immunological memory from the foreign genetic elements and storing it in the genome, (ii) retrieving this immunological memory in the form of RNA and (iii) using this RNA as a guide for target recognition and cleavage. This talk will introduce CRISPR-Cas as a prokaryote-specific defense response and highlight the molecular mechanism that underlie the fascinating functional diversity. Finally, I will provide a compelling narrative how mechanistic understanding of this defense system was instrumental for repurposing them as precision genetic scissors.