Ilya Finkelstein, University of Texas
Host: Roger Loring
Single-molecule views of bacterial adaptive immunity
Clustered regularly interspaced short palindromic repeats (CRISPRs) are a recently discovered RNA-based adaptive immune system that protects bacteria and archaea from foreign DNA and play a central role in controlling horizontal gene transfer. More recently, CRISPR-associated (cas) proteins have been harnessed for programmable gene regulation and precision genome editing. All CRISPR systems require complementary base pairing between an RNA-guided nucleoprotein complex and the target DNA. Off-target activities have also been reported, but we currently lack a comprehensive and quantitative description of sequence-dependent DNA binding and nuclease activation. I will discuss our recent progress in using a combination of single-molecule biophysics and next-generation sequencing to uncover the mechanisms of target recognition and DNA degradation by a variety of CRISPR systems. This work offers new insights in understanding the mechanisms of CRISPR-associated adaptive immunity and for using these enzymes for precision genome engineering in both scientific and future therapeutic settings.
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