iiinova — where your digital self keeps evolving

Jacob Corn @jcornlab.bsky.social · 30/06/2026

Do you need a super active #CRISPR Cas for in vivo editing? I have not one, but two options for you. Activities rival SpyCas9, but they fit into an scAAV. Check out our latest paper, co-led by Fedor Gorbenko and Irene Sala. Just out in Genome Research. link.springer.com/article/10.1...

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Jacob Corn @jcornlab.bsky.social · 18/03/2026

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!

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Jacob Corn @jcornlab.bsky.social · 18/03/2026

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.

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Jacob Corn @jcornlab.bsky.social · 18/03/2026

Using cryo-EM and AlphaFold, we found that SP110 physically binds SP100 via their CARD domains. In healthy cells, this interaction sequesters SP100 and dissolves PML bodies in mitosis. Without SP110, SP100 oligomerizes and wreaks havoc on the genome.

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Jacob Corn @jcornlab.bsky.social · 18/03/2026

What happens when SP110 is missing? SP100 becomes a "toxin." When upregulated, it forms large oligomers that fail to disassemble and persist into mitosis. These persistent SP100-PML bodies coat segregating chromosomes, causing massive DNA damage and genomic instability.

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Jacob Corn @jcornlab.bsky.social · 18/03/2026

The story started with a genome-wide CRISPRi screen for regulators of the innate immune response. We found that SP110 is a potent inhibitor of interferon-driven cell death. It specifically counteracts the toxic activity of another speckled protein, SP100.

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Jacob Corn @jcornlab.bsky.social · 18/03/2026

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/s415...

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Jacob Corn @jcornlab.bsky.social · 12/03/2026

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.

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Jacob Corn @jcornlab.bsky.social · 12/03/2026

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.

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Jacob Corn @jcornlab.bsky.social · 12/03/2026

Many genome-editing tools work by cutting DNA - but the shape of the cut matters. Using genome-wide screening, we show ERCC6L2 is specifically required to maintain repair fidelity at staggered DNA breaks, but not at blunt ends. www.nature.com/articles/s41...

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Jacob Corn @jcornlab.bsky.social · 22/11/2025

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

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Jacob Corn @jcornlab.bsky.social · 17/11/2025

Congratulations to @sebasiegner.bsky.social who defended his PhD on Friday! His name will be on 6-7 papers by the time he leaves the lab, including a co-first Nature paper. What a superstar! Keep an eye out for his postdoc application 😉

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Jacob Corn @jcornlab.bsky.social · 10/11/2025

Congrats to Moritz Schlapansky, who successfully defended his PhD thesis on Friday! You can read his work on "scOUT-seq" profiling of single cell transcriptomes + editing outcomes in millions of cells and living mice at www.biorxiv.org/content/10.1...

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Jacob Corn @jcornlab.bsky.social · 12/02/2025

Altogether, proximity is key and search normally stays around the DSB. When it comes choosing a donor, only these sequences are candidates.

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Jacob Corn @jcornlab.bsky.social · 12/02/2025

During genome editing, exogenous donor DNAs soak up homology search during HDR. Even if they have no sequence relationship to the cut site at all. They actually steal search from the genome!

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Jacob Corn @jcornlab.bsky.social · 12/02/2025

Only 3D-nearby those sequences that are searched (i.e., candidates) are chosen as HDR donors! Donors too far away are never seen and never used.

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Jacob Corn @jcornlab.bsky.social · 12/02/2025

Search is constrained by chromatin conformation. Check out the related preprints from fedeteloni.bsky.social and albertomarin.bsky.social for a much deeper dive (see later in thread).

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Jacob Corn @jcornlab.bsky.social · 12/02/2025

We call this "RaPID-seq". It unveils a new dimension of DNA repair, telling us what is searched during HDR. In other words, what are the candidates?

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