This story is from the same Eric Aird who just published on the role of ERCC6L2 at staggered DSBs. The guy is on fire! And starting to plan his next steps afer his postdoc (hint hint to anyone looking to hire an amazing scientist and mentor).
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.
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.
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.
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.
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...
The E3 ubiquitin ligase mechanism specifying target-directed microRNA degradation (TDMD) is now published! 🎉🍾 We, @bartellab.bsky.social and Schulman lab, describe how 2-RNA factors control protein degradation by recruiting an E3 ligase. @mpibiochem.bsky.social
www.nature.com/articles/s41...
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.
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.
This work was led by Eric Aird, almuseben.bsky.social and sebasiegner.bsky.social in an amazing collaboration w/ spjacksongroup.bsky.social, cejkalab.bsky.social, Toni Cathomen and IBSAL.
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...
It’s been a fun first few week of my sabbatical. Many exciting meetings w/ @peterfineran.bsky.social 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…
Dunedin welcomed me to my sabbatical at @universityofotago.bsky.social with @peterfineran.bsky.social with style.
I’m an @univpugetsound.bsky.social alum. Super cool to see UPS STEM highlighted. 10/10 would recommend. Liberal arts education FTW.
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.
ERC Plus Grants
• No career limit, current ERCs are not eligible
• Major challenge, transformative research
• Up to 7 million euros, up to 7 years
• 30 grants per year, 2 years, only once per lifetime
• Same application format, plus vision statement
• Deadline in September 2026, 2 stage evaluation
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 @sebasiegner.bsky.social and @matthiasmuhar.bsky.social that reads out repeat sequence. www.biorxiv.org/content/10.1...
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!
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 😉
Reposted in edited form b/c I realized my original post could have been misinterpreted.
I recently received an AI-generated referee report. Almost all suggested experiments were already main figures & referee admitted using AI when asked by the editor. But they claimed they only used AI to write. No way. Editors, what do you do in this case? Referees, at least read the paper!
For me, it was the referee who used AI. Though AI generated papers and edits are certainly a problem.
I just realized my original post could be read the wrong way. Paper was from my lab and out for review in a high profile journal. Four years of work by a dozen people in multiple labs and AI slop seem to have been the judge.
It has been disappointing to see the general lack of interest and investment into population genetics and genomic medicine in Switzerland. While we can resort to other national cohorts for research the country can only benefit if the know-how can be applied locally
www.sfa-phrt.ch/success-stor...
957 proposals were submitted in the latest round of ERC Synergy applications. They expect to fund 50 which means around 5% success rate. This is really not sustainable and a lot of people are likely avoiding doing this knowing how poor the chances are.
erc.europa.eu/news-events/...
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...
In 2026 I'm taking a sabbatical in @peterfineran.bsky.social lab @universityofotago.bsky.social. I'm looking forward to learning a lot from Peter's lab and excited to get back to my prokaryotic/viral roots! Also planning to some trips to the rest of the Pacific and Asia. So much to look forward to!
This was a great collaboration with the lab of Virginijus Siksnys!
