Postdoc in the Kruse lab, @HMS_BCMP previously @doudna_lab / Kuriyan lab grad student in @berkeleyMCB
Boston, MA
Joined September 2021
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Josh Cofsky retweeted
Here, @JoshCofsky, @doudna_lab, and colleagues, use #CryoEM and biochemical analysis to investigate how the #CRISPR associated protein #Cas9 interrogates DNA to locate its RNA-matching target sequence @berkeleyMCB @igisci nature.com/articles/s41594-0…
Have you ever wondered how A-form and B-form nucleic acid helices might interact with each other during the expansion of a Cas9-bound R-loop? Check out our crystal structure of an interhelical stack in @PLOSONE ! #stacked
🙏 @doudna_lab @gavinjknott +CLG
dx.plos.org/10.1371/journal.…
"A tweak and a peek"! Our Cas9 paper is now out in @NatureSMB (nature.com/articles/s41594-0…). Thanks also to Sinan + Russell for the News & Views article (nature.com/articles/s41594-0…), which nailed it with the title and the beautiful explanations :)
🙏@doudna_lab @gavinjknott @NogalesLab
Josh Cofsky retweeted
1. I am thrilled to share the accepted version of our Cas9 mismatch manuscript, now in @Nature! Here’s a (not-so) brief outline of some of the findings from our original preprint, and some VERY exciting new findings nature.com/articles/s41586-0…
The first crystal structure I solved myself, no thanks to some pesky diffraction anisotropy! With crucial help from @gavinjknott, Christine Gee, and @doudna_lab, of course. If you don't care about nucleic acid structure, just check out the sexy lattice architecture in Fig. 1 😍
Crystal structure of an RNA/DNA strand exchange junction biorxiv.org/cgi/content/shor… #bioRxiv
Josh Cofsky retweeted
Keeping the ball rolling with my next manuscript from the @MartinJinek lab! We solved several
structures of intermediary binding states of Cas9 to elucidate the mechanism of target DNA binding and conformational activation!
biorxiv.org/content/10.1101/…
Josh Cofsky retweeted
(1/2) Cas9 can cut off-targets. We used kinetics-guided structural studies of Cas9 bound to different mismatches and reveal DNA bending requirements for targeting, the non-target strand poised for cleavage in the active site of RuvC, and… biorxiv.org/content/10.1101/…
New pre-print! While #CRISPR-Cas9 searches through the genome, how does it actually "read" DNA sequence information, which is normally hidden within the double helix? We determined structures of Cas9 in the act of DNA interrogation to find out! Thread below 👇 (1/8)
The speed with which Cas9 performs these bending actions may determine how fast it can find its target. Also, Cas9 may interact differently with pre-bent DNA sequences (such as those wrapped around histones). Both important considerations for genome editing efficiency! (7/8)
Thanks to @berkeleyMCB and all my wonderful co-authors (Kasia Soczek, @gavinjknott, @NogalesLab, @doudna_lab) for making these discoveries possible and teaching me a thing or two about structural biology 🧬 (8/8)