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Nicholas Perry
76 posts
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Nicholas Perry
@ntperry13
Applying Claude to Life Sciences @AnthropicAI
Palo Alto, CA
Joined August 2018
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  • user avatar
    Nicholas Perry
    @ntperry13
    Jun 26, 2024
    Our work on bridge recombination is out in @Nature today. We are especially excited to share our structural work in collaboration with @hnisimasu. We show that this enzyme makes and breaks a Holliday junction, using more (!) RNA-DNA base-pairing to drive the reaction forward 🧵
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  • user avatar
    Nicholas Perry
    @ntperry13
    Jul 7, 2025
    Happy to share that I'm continuing my research on bridge recombinases as a scientist in @pdhsu lab at the @arcinstitute! I am looking for a motivated post-grad to work with me as a research associate. If you are interested or know of someone, please use the link below:
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  • user avatar
    Nicholas Perry
    @ntperry13
    May 15, 2025
    "Does it work in human cells?" is a question I've gotten a lot this past year. Excited to share our latest work on bridge recombinases! It's been a lot of fun to lead this team effort. If you are excited to hear more, join for my thesis defense tomorrow at 3pm PT. Links below:
    user avatar
    Patrick Hsu
    @pdhsu
    May 15, 2025
    Genomes encode biological complexity, which is determined by combinations of DNA mutations across millions of bases In new @arcinstitute work, we report the discovery and engineering of the first programmable DNA recombinases capable of megabase-scale human genome rearrangement
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  • user avatar
    Nicholas Perry
    @ntperry13
    Jan 26, 2024
    Amazing week @KeystoneSymp ! So much fun to finally share our work. It’s been an awesome scientific journey characterizing this system with @mgdurrant and our team Some notes on our bridge recombination system from our preprint 🧵:
    user avatar
    Patrick Hsu
    @pdhsu
    Jan 25, 2024
    Just shared at @KeystoneSymp a new @arcinstitute discovery of the bridge RNA recombinase mechanism: a new class of natural RNA-guided systems that retains the key property of programmability from RNAi and CRISPR while enabling large-scale genome design beyond RNA and DNA cuts
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  • user avatar
    Nicholas Perry
    @ntperry13
    Jun 26, 2024
    Excited for our papers out in @Nature today! Please read this excellent thread by @pdhsu. Incredible teamwork was required for all this work to come together. Especially thankful to my co-lead @mgdurrant, and our collaborators at University of Tokyo @hnisimasu and @somturn20
    user avatar
    Patrick Hsu
    @pdhsu
    Jun 26, 2024
    What if we could universally recombine, insert, delete, or invert any two pieces of DNA? In back-to-back @Nature papers, we report the discovery of bridge RNAs and 3 atomic structures of the first natural RNA-guided recombinase - a new mechanism for programmable genome design
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  • user avatar
    Nicholas Perry
    @ntperry13
    Jan 25, 2024
    Replying to @markwbudde @pdhsu and 2 others
    We extensively utilized @PrimordiumLabs and @plasmidsaurus in this work. Extremely enabling for this kind of project!
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  • user avatar
    Nicholas Perry
    @ntperry13
    May 15, 2025
    Replying to @ntperry13
    arcinstitute-org.zoom.us/j/82812357615?… biorxiv.org/content/10.110…
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    Join our Cloud HD Video Meeting
    From arcinstitute-org.zoom.us
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  • user avatar
    Nicholas Perry
    @ntperry13
    May 15, 2025
    Replying to @owl_posting
    would love to connect with you to explain!
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  • user avatar
    Nicholas Perry
    @ntperry13
    Jan 26, 2024
    Replying to @ntperry13
    On the mobile genetic element side: - They are abundant in bacteria and archaea - They are cut and paste elements - The recombinases are ~325 aa - The bridge RNA is ~177 nt - The bridge RNA binds to both strands of the target and donor DNA (not one strand like CRISPR systems)
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  • user avatar
    Nicholas Perry
    @ntperry13
    Jan 26, 2024
    Replying to @ntperry13
    Matt and I would love to teach you more about how these systems work. Please reach out if you’d like to learn more! [email protected] mattdurrant.me Also, we are recruiting!
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  • user avatar
    Nicholas Perry
    @ntperry13
    Jun 26, 2024
    Replying to @ntperry13
    Another remarkable mechanism of this enzyme, we think it may have evolved to control directionality of the recombination reaction. We have built the handshake guide reprogramming rules into our bridge RNA design tool, which you can find here:
    Arc Institute
    Bridge RNA Design Tool | Arc Institute
    From arcinstitute.org
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  • user avatar
    Nicholas Perry
    @ntperry13
    Jan 26, 2024
    Replying to @ntperry13
    On the genome design side: - The bridge RNA, target, and donor sequences can be reprogrammed independently - This system can catalyze insertion, inversion and excision, like Cre-loxP - Insertions are stranded, meaning you can choose the orientation of the cargo upon insertion.
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  • user avatar
    Nicholas Perry
    @ntperry13
    Dec 5, 2024
    Congratulations Alison! Looking forward to seeing what people do with your engineered integrases in stem cells and T cells. Check out @AlisonFanton exciting thesis work here: biorxiv.org/content/10.110… nature.com/articles/s4158…
    user avatar
    Patrick Hsu
    @pdhsu
    Dec 5, 2024
    Super proud of the fearless @AlisonFanton for her PhD defense yesterday! Alison is a super talented bioengineer and molecular biologist who has done pioneering work on DNA recombinases for human genome insertion. Congratulations, Dr. Fanton!
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  • user avatar
    Nicholas Perry
    @ntperry13
    Jun 26, 2024
    Replying to @ntperry13
    We show two recombinase dimers bind one loop each of two (separate) bridge RNA molecules. These RNPs bind DNA and come together to form a tetramer. Composite active sites form between opposing dimers, using all five catalytic residues to facilitate strand cleavage
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