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Posts by Sebastian Siegner

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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...

1 month ago 20 13 1 0
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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...

1 month ago 16 5 1 0

Happy to share our new pre-print on the dependency of ALT-positive tumors on the DNA translocase SMARCAL1. Outstanding work of @angelotaglialatela.bsky.social in collaboration with the Min, Lazzerini Denchi and @cejkalab.bsky.social laboratories! www.biorxiv.org/content/10.6...

2 months ago 20 9 0 0
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a man wearing a beanie and a black jacket is smiling and holding a piece of food . ALT: a man wearing a beanie and a black jacket is smiling and holding a piece of food .

Very cool work published in @science.org led by OanaPelea,
happy to participate!

www.science.org/doi/10.1126/...

2 months ago 2 1 0 0
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Excited to share our new Nature study! 🧬

We (sidrituruci.bsky.social et al) discovered that CFAP20 helps clear stalled RNAPII, preventing harmful clashes with DNA replication machinery. This protects cells from R-loops and genome instability.

Full paper: www.nature.com/articles/s41...

3 months ago 65 22 5 2
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One more upcoming appointment with great science via the Genome Integrity Italian Network (GiiN). Don't miss it, just join via the link πŸ‘‡

3 months ago 11 7 0 1
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New research group leader for functional genomics Molecular biologist Matthias Muhar becomes part of the MPI-CBG faculty

New research group leader @matthiasmuhar.bsky.social joins @mpi-cbg.de! πŸ₯³ With his group "Functional genomics of proteome remodeling,” Matthias wants to pursue high-throughput genetic studies to understand how protein turnover is regulated. Welcome, Matthias! www.mpi-cbg.de/news-outreac...

4 months ago 43 15 0 1
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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...

5 months ago 2 2 0 0
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Directed evolution of compact RNA-guided nucleases for homology-directed repair in mammalian cells RNA-guided nucleases enable DNA editing and offer promise for treating genetic diseases, particularly when used for precise sequence replacement. However, many of the most effective enzymes, such as S...

Sometimes #Cas9 is too dang big. But mini Cas proteins are bad at both NHEJ & HDR. PhD student Fedor Gorbenko used mammalian cell evolution for *HDR* to make REALLY super #Cas12f1 and #TnpB. As good as or better than Cas9! Base editors included! www.biorxiv.org/cgi/content/short/2025.10.27.684765v1

5 months ago 9 3 1 0
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An ETH spin-off aims to bring gene scissors to the clinic Thanks to CRISPR/Cas technology, researchers can precisely edit genetic material to treat hereditary diseases. To achieve this, they need to identify undesirable cuts in the genome at an early junctur...

Thanks to CRISPR/Cas technology, researchers can precisely edit genetic material to treat hereditary diseases. To achieve this, they need to identify undesirable cuts in the genome at an early juncture. Pioneer Fellow Lilly van de Venn is developing such testing methods. ethz.ch/en/news-and-...

5 months ago 5 3 1 0
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Cell-stereotyped DNA repair outcomes are widespread during genome editing Genome editing outcomes are governed by DNA repair pathways that vary with cell type and state. We developed scOUT-seq (single-cell Outcomes Using Transcript sequencing), a scalable approach that join...

Ever noticed that #CRISPR editing results differ between cells? Awesome PhD student Moritz Schlapansky developed "scOUT-seq" to measure single cell transcriptomes + editing. 1.2 million cells, 74 cell types, living 🐭. Cell subtypes differ wildly from bulk average! www.biorxiv.org/content/10.1...

5 months ago 18 11 3 0

On that note: hello world! My new lab on genetics of proteome remodeling is starting at the incredible MPI-CBG. We have big plans and open positions for PhD students and an RA. Apply now (!) at imprs.mpi-cbg.de and tinyurl.com/2vywj6f6 respectively.

5 months ago 10 5 2 0
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If you are interested in a PhD in the area of "Mechanisms of Genome Stability" and "Functional Genomics of Proteome Remodelling," apply now for a PhD @mpi-cbg.de! Overview of all participating RGLs: imprs.mpi-cbg.de/5761/researc...

6 months ago 5 3 0 1
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Just out in @science.org: Together with the lab of @wilhelmpalm.bsky.social, we used sequential in-vitro/in-vivo CRISPR screens to decipher metabolic adaptations in tumors. We find that acidosis is a dominant factor that shapes energy metabolism and stress resilience. www.science.org/doi/10.1126/...

6 months ago 110 29 1 3
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Happy to share our latest research on the BRCA1-BRCTs now online.

academic.oup.com/nar/article/...

Congrats to first author Venda for putting it all together! This project was a great collaboration with the @titiasixma.bsky.social lab who helped us give structural meaning to our observations.

7 months ago 19 6 1 1
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Mitotic single-stranded DNA suppression by DDIAS Incomplete DNA replication and chromosome breakage during mitosis pose major threats to chromosome segregation. The CIP2A-TOPBP1 complex acts to mitigate this peril, but its exact role is not yet unde...

New work from the lab! πŸ”¬

We report that DDIAS is a new component of the mitotic CIP2A-TOPBP1 pathway of genome maintenance. 1/n

www.biorxiv.org/content/10.1...

7 months ago 47 17 2 0
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JOB ALERT 🚨 We are hiring TWO principal investigators in cell, molecular, systems, or chemical biology in Toronto, Canada at @sinaihealth.bsky.social. We provide a generous startup, fully funded salary and academic appointment at U of Toronto.

www.nature.com/naturecareer...

Please repost!

7 months ago 133 169 0 8
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Exciting to see our protein binder design pipeline BindCraft published in its final form in @Nature ! This has been an amazing collaborative effort with Lennart, Christian, @sokrypton.org, Bruno and many other amazing lab members and collaborators.

www.nature.com/articles/s41...

7 months ago 305 109 14 11

Exciting times ahead!

Today marks the first day of the Loeff Lab at Leiden University Medical Center in the Netherlands πŸ‡³πŸ‡±. I’m thrilled to begin this new adventure and continue exploring microbial defense mechanisms and their applications through an integrative structural biology approach.

8 months ago 65 9 10 1
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NASP modulates histone turnover to drive PARP inhibitor resistance - Nature PARP inhibitor treatment triggers histone release from the chromatin in cancer cells; consequently, targeting the histone chaperone NASP renders cells vulnerable to PARP inhibition.

Thrilled to share our latest work, just published in @nature.com ⬇
www.nature.com/articles/s41...

We discovered that PARP inhibitors πŸ’Š trigger histone eviction from the chromatin and this creates a hidden vulnerability in PARPi resistant tumors.
🧡 (1/8)

8 months ago 82 32 3 3
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Multigenerational cell tracking of DNA replication and heritable DNA damage - Nature A multigenerational single-cell tracking approach provides a framework to dissect phenotypic plasticity at the single-cell level, offering insights into cellular processes that may resemble early even...

Delighted to share that the results of my main postdoc project are now published in @nature.com

πŸ”— doi.org/10.1038/s415...

10 months ago 89 34 8 1
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Treatment of a metabolic liver disease in mice with a transient prime editing approach - Nature Biomedical Engineering A transient in vivo prime editing strategy is developed for the liver by delivering the prime editor as mRNA encapsulated in LNP.

Our paper describing an RNA-LNP prime editing strategy for treating phenylketonuria was published today in Nature Biomedical Engineering (1/7)
www.nature.com/articles/s41...
@schwanklab @UZH_Science @UZH_en @KispiZuerich @ethz.ch

11 months ago 6 4 1 0
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Exciting PhD project available in our lab (time sensitive)! πŸ‘‡

11 months ago 10 15 1 0
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Comprehensive interrogation of synthetic lethality in the DNA damage response Nature - Combinatorial CRISPRi screening was used to map genetic interactions in DNA damage response pathways, revealing known and new connections, including the roles of WDR48 and USP1 in...

Thrilled to see this β€œveritable tour de force” led by John_C_Fielden from Jacob Corn lab out @nature.com, rdcu.be/ehd4E. This @erc.europa.eu funded project uses #CRISPRi to systematically scan 548 DDR genes for synthetic lethal interactions, ~150,000 pairwise combinations!

1 year ago 10 5 1 0

New #preprint from the lab! Do you want to see the invisible? So did we! When DNA genomes get broken, cells somehow find related sequences to fix the break. But how do they find it? We developed a way to look at sequence *search*, not just sequence usage.
doi.org/10.1101/2025...

1 year ago 34 22 2 1
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Very cool study about selective protein degradation by FBXO31!

1 year ago 3 1 0 0