Jacob Corn

We saw the same SP100-dependent toxicity in cells from VODI patients who lack SP110. Regulated condensate disassembly may be a general requirement for maintaining cellular health!

This phenomenon is relevant to any situation where the balance of SP110 versus SP100 expression is perturbed. Not just via interferon upregulation. SUMOylation is also a key regulator of toxicity.

Proper organelle regulation during mitosis is a must, but how do membrane-less condensates like PML bodies behave during cell division? In work led by @eric_aird, we found the balance of speckled proteins SP110 & SP100 to be the key. doi.org/10.1038/s41556…

@ketanpatelimmo1 @karasuerman1 Excellent question. Maybe increased demand for NHEJ in HSCs plus more frequent overhanging ends vs blunt? No clear source of increased overhangs in HSCs so far as I know. My lab is more and more getting into tissue-specific etiologies of mutations in core repair factors.

@jcornlab @karasuerman1 But why should its loss lead to bone marrow failure?

Many genome-editing tools work by cutting DNA - but the shape of the cut matters. Using #CRISPR screening, we show ERCC6L2 is specifically required to maintain #DNArepair fidelity at staggered DNA breaks, but not at blunt ends. nature.com/articles/s4146…

@eric_aird @almuseben @SMSiegner @SPJacksonGroup @CejkaLab ERCC6L2 acts as a guardian during repair of staggered DSBs. This sheds light on ERCC6L2 mutations linked with BMF and leukemia and highlights caution for genome-editing approaches that generate DNA overhangs.

@eric_aird @almuseben @SMSiegner @SPJacksonGroup @CejkaLab What does ERCC6L2 actually do? It counteracts the activity of the MRN complex (MRE11–RAD50–NBS1), limiting excessive DNA end resection and promoting accurate end joining.

It’s been a fun first few week of my sabbatical. Many exciting meetings w/ @PeterFineran lab, learning new stuff and brainstorming ideas. And my own lab has been off to a crazy great start to the year. The early/late zoom meetings have me burning the candle at both ends…

Happy to share that my postdoctoral work is now out in @ScienceMagazine. We show that the RNA-programmable bridge recombinase ISCro4 can insert, delete, or invert multi-kilobase DNA fragments at defined genomic sites in human cells. Study link: science.org/doi/10.1126/sc… CRISPR-Cas has transformed genome editing, but many diseases involve diverse patient-specific mutations within the same gene. A mutation-agnostic alternative is to insert a healthy gene copy at a defined genomic locus, but gene-sized, site-specific insertions remain a major challenge. Main findings of our work: (1) ISCro4 is highly active in human cells and can be delivered by plasmid or all-RNA formats (2) Proof-of-concept programmable multi-kb insertions, deletions, and inversions (3) Structural insights into the basis of enhanced ISCro4 activity (4) Specificity and off-target characterisation (5) A framework to support future development and adoption of bridge recombinases The work was made possible through a close collaboration between the Jinek Lab, @schwanklab, and @jcornlab. I am deeply grateful to all of my co-authors for the team spirit, hard work, and dedication that went into this publication: @talasandris, Javier Fernández Carrera, @nicopmat, Lilly van de Venn, Charles Yeh, @p_kulcsar, @marquark, @YanikWeber, @SaskiaGerecke, Isabelle Harvey-Seutcheu, Dominic Mailänder, @MorPfl, and @ChrisChanez89. Special thanks to my supervisor, Prof. Martin Jinek, for his outstanding mentorship, and to Prof. Gerald Schwank and Prof. Jacob Corn for their generous support throughout. Finally, I would like to thank everyone in the Jinek lab for creating a supportive work environment, and @EMBO for funding my postdoctoral work. In parallel, independent work led by @ntperry13, @SKonermann and @pdhsu also reported ISCro4 activity in human cells, reinforcing the robustness and momentum of this direction. Please reach out if you would like to test the system or discuss potential applications. Relevant plasmids are now available via @Addgene.

This looks incredible! Cell systems can still be a bottleneck, but are cloning woes now a thing of the past?

Dunedin welcomed me to my sabbatical at @otago with @PeterFineran with style

AI reviewers are here — we are not ready nature.com/articles/d4158…

Sometimes I'm excited to read a paper and every paragraph blows me away. And sometimes I'm just as excited and every paragraph leaves me wondering if the referees were sleeping on the job. Today it was one of the latter.

1/ New preprint out! We show that PROTAC-induced ubiquitination can bypass canonical ERAD to degrade ER membrane proteins. Wonderful collaboration w/ @DanNomura and huge credit to grad student superstar Sydney Tomlinson! biorxiv.org/content/10.110…

What controls expansion & contraction of DNA repeats (e.g. Huntington's)? We were thrilled to collaborate w/ the lab of Marta Olejniczak to find out. Check out the cool screen from @SMSiegner and Matthias Muhar that directly reads out repeat sequence. biorxiv.org/content/10.110…

I’m very grateful to @ETH_en @vseth for a Golden Owl award. People who know me know that I respectfully decline science awards. But recognition directly by students hits different!