Sebastian Siegner

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...

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

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-...

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...

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.

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...

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/...

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.

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! 🔬

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...

Image of Toronto

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!

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...

Exciting times ahead!

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

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 💊 trigger histone eviction from the chromatin and this creates a hidden vulnerability in PARPi resistant tumors.
🧵 (1/8)

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

🔗 doi.org/10.1038/s415...

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

Exciting PhD project available in our lab (time sensitive)! 👇

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 “veritable 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!

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...

Very cool study about selective protein degradation by FBXO31!