Lab News

Camilla Micheli obtained her Bachelor’s degree in Biology from Maastricht University (UM) in 2024. She is currently enrolled in the Microbiology and Immunology Master’s program at ETH Zurich. In the spring of 2025, Camilla carried out a semester project in the Corn Lab, where she assessed the fidelity of base editing sensors in breast epithelial cells. In March 2026, she returned to the lab to begin her Master’s thesis, which focuses on characterising the mechanism of putative oncohistone driver mutations.

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Programmable nucleases have transformed genome editing, enabling precise DNA modification for both research and therapeutic applications. However, ensuring that these tools cut only at their intended target—and not elsewhere in the genome—remains a key challenge, particularly for clinically relevant platforms where accurate off-target detection is essential.

In our latest collaboration with the Genome Engineering and Measurement Lab (GEML) and Allogene Therapeutics, we introduce DisTAL-Seq, a method that enables genome-wide detection of TALEN-induced DNA double strand breaks directly in human cells. The experimental work was led by research technician Lena Kobel. This approach builds on the principles of DISCOVER-Seq and incorporates analysis logic tailored to TALEN binding architecture, including variable repeat specificity, cleavage offset, and dimerization behavior.

Using DisTAL-Seq, we identified and validated editing sites across different TALEN designs and primary human T-cell donors, providing a systematic view of TALEN specificity in clinically relevant contexts.

These results expand the genome-wide profiling approaches developed at GEML and provide a framework for evaluating the safety and performance of genome editing nucleases as they move towards therapeutic applications.

For more detail, check out our paper in Molecular Therapy: Nucleic Acids.

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Stimulation of the innate immune system by foreign RNA triggers a strong interferon response that helps cells defend against infection. However, this powerful defense mechanism can also lead to cell death if not properly controlled. How do cells maintain this delicate balance?

Our latest breakthrough was led by postdoc Eric Aird in collaboration with the Hale Lab (University of Zurich), Recher Lab (University of Basel, University Hospital Basel), Jackson Lab (UCAM) and University of Kuwait.

Using genome-wide CRISPR screens and follow-up cellular biochemistry experiments, we discovered that speckled protein 110 (SP110) functions as a key safeguard against cell death triggered by interferon signaling.

Mechanistically, the study revealed that SP110 interacts with the nuclear body protein SP100 to regulate the disassembly of nuclear promyelocytic leukemia (PML) bodies. Loss of SP110 made cells highly sensitive to interferon stimulation, led to mitotic retention of SP100 and PML bodies, which associated with and perturb segregating chromosomes, leading to micronucleus formation, DNA damage and genotoxic cell death. Conversely, restoring SP110 protected cells from this lethal response. The SP100-SP110 axis is molecularly achieved by newly described functions for the SP100 and SP110 CARD domains that mediate assembly and disassembly of SP100 oligomers. By controlling this process, SP110 helps maintain a balance between effective immune signaling and cell survival.

These findings highlight regulated disassembly of phase-separated biomolecular bodies as essential for cell health and that its failure may contribute to diverse human diseases.

For more details, please visit Nature Cell Biology!

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DNA double-strand breaks (DSBs) are among the most dangerous forms of DNA damage, threatening genome stability but also serving as essential intermediates for many genome-editing technologies. A key question in the field is how cells repair different types of DSBs and what factors ensure that repair outcomes remain accurate.

In our new study, we uncover an important role for the DNA repair factor ERCC6L2 in safeguarding the repair of staggered DNA breaks, a type of DSB produced by several genome-editing tools. This exciting new work way led by our postdocs Eric Aird and Sebastian Siegner together with Almudena Serrano-Benítez from the Jackson lab (UCAM), together with the Cejka (USI) and Cathomen groups and colleagues from the University of Freiburg and IBSAL.

Using genome-wide CRISPR interference (CRISPRi) screening, we identified ERCC6L2 as a critical factor required for accurate repair of staggered DSBs generated by Cas12, TALENs, or dual Cas9 nicks. Interestingly, ERCC6L2 was not required for repairing the blunt DSBs typically produced by Cas9, revealing that different break structures rely on distinct repair mechanisms.

We found that ERCC6L2 protects staggered DNA ends and prevents harmful repair outcomes such as large deletions and chromosomal translocations. Mechanistically, ERCC6L2 counteracts the activity of the MRN complex (MRE11–RAD50–NBS1), limiting excessive DNA end resection and promoting accurate end joining.

Loss of ERCC6L2 sensitized cells to damage caused by multiple staggered breaks and increased genome instability following genome editing. These findings highlight ERCC6L2 as an important guardian of genome integrity and provide new insight into how cells respond to structurally diverse DNA breaks.

Beyond fundamental DNA repair biology, this work also has practical implications for genome engineering. Because many editing systems create staggered DNA ends, understanding how ERCC6L2 shapes repair outcomes may help improve editing accuracy and guide the safe use of these tools, particularly in therapeutic contexts. Our data reveal a protective role of ERCC6L2 in staggered-end DSB repair, shedding light on the molecular basis of pathology of ERCC6L2 mutations, which in humans most commonly present as inherited bone marrow failure and leukemia. The findings also suggest caution when considering therapeutic genome-editing strategies that rely on nucleases generating DNA overhangs for their treatment.

For more info, check out our new paper in Nature Communications!

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In February 2026, as part of the ETH Postdoc Career Week, the ETH Grants Office hosted a session on postdoctoral funding opportunities.

Ana, our Program Manager, was invited to share insights into her career path and to highlight the collaborative Horizon projects involving the Corn Lab and GEML. The session also emphasized how securing third-party funding can be a powerful catalyst for advancing your research career. You can find the slides here.

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We are proud to share that Jacob has received the 2025 Golden Owl Award for Excellent Teaching, presented by the student association VSETH. This award recognizes outstanding dedication to teaching, as nominated and selected by students. Congratulations to Jacob on this well-deserved recognition!

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David received his PhD in Molecular Life Science at the University of Zürich in 2025, working in the lab of Prof. Ataman Sendoel. For his PhD thesis David studied early embryonic development in an organoid model using single-cell CRISPR screens. In January 2026, David joined Corn lab as Genomics Expert, where he will support lab NGS and single-cell sequencing projects and act as link to the FGCZ.

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One of our postdocs, Matthias Muhar, secured a group leader position at the Max Planck Institute of Molecular Biology and Genetics in Dresden, Germany in November 2025 and will set up his own research group in “Functional genomics of proteome remodeling”. His lab will study how cells remodel their proteome during differentiation. His research will combine high-throughput genetics, proteomics, and chemical biology approaches to understand how protein homeostasis is regulated in neurons and other highly specialized cells of the human body. We wish him every success as he embarks on this next chapter and look forward to the exciting developments ahead for his new lab!

More information on the research focus of Matthias’s group can be found here.

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We are delighted to announce that Fedor has successfully defended his PhD. During his doctoral research, Fedor demonstrated remarkable dedication and perseverance, focusing on the directed evolution of RNA-guided nucleases to enhance homology-directed repair (HDR) in mammalian cells. His outstanding work advances the precision and efficiency of genome editing, contributing valuable tools to the fields of functional genomics and therapeutic gene correction. Congratulations, Dr. Gorbenko!

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We are happy to announce that Seba has successfully completed his PhD, built on passionate and persistent research into synthetic lethality in the DNA damage response —research that deepens our understanding of how cells cope with genetic stress. Cheers. Dr. Siegner!

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