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Slideshow

CRISPR-Cas systems and their Interaction with Bacteriophage

Dr. Andrew Varble
Dr. Andrew Varble
Marraffini Laboratory
The Rockefeller University
Online via Zoom
Special Information:
Please contact Nancy Perkins at nancydh@uga.edu for Zoom link and passcode
Type of Event:
Department Seminars

Abstract:

CRISPR loci are composed of short DNA repeats separated by sequences that match the genomes of phages and plasmids, known as spacers. Spacers are transcribed and processed to generate RNA guides used by CRISPR-associated nucleases to recognize and destroy the complementary nucleic acids of invaders. My postdoctoral work focused on 2 elements of this immune response: (1) Although, CRISPR-cas loci are widely distributed throughout microbial genomes and often display hallmarks of horizontal gene transfer, the drivers of CRISPR dissemination remain unclear. I show that spacers can recombine with phage target sequences to mediate a form of specialized transduction of CRISPR elements. (2) To counteract CRISPR defense, phages can produce small proteins that inhibit these nucleases. I demonstrate that the ΦAP1.1 temperate phage first expresses a canonical anti-CRISPR, to prevent Cas9 function, and then integrates into the direct repeats of the CRISPR locus to neutralize immunity during lysogeny. Building on these findings, I plan to characterize the interaction between CRISPR immunity and horizontal gene transfer, while also expanding this dynamic to determine wide-ranging mechanisms and barriers to horizontal gene transfer and how this impacts the pathogenicity of Staphylococcus and Streptococcus organisms.

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