Lab News

Rafaela received her Master’s degree in Bioengineering from the University of Engineering of Porto in 2019, where she worked on the production and characterization of Anti-CCR5 siRNA-loaded nanoparticles for topical pre-exposure prophylaxis of HIV-1 infection. Later on, she joined Adriano Aguzzi’s lab at the University of Zurich as a research technician/assistant, focusing on CRISPR screens and hit validation in neurodegenerative diseases. Rafaela joined the Corn Lab as a scientific assistant in February 2025. Her research interests include studying complete organelle removal during erythropoiesis.

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Boris Korablev received his Bachelor’s degree in Molecular and Cell Biology from UC Berkeley in 2021. Before joining ETH, he worked at a gene-editing startup in the Bay Area. In February 2025, Boris joined the Corn Lab for his Master’s thesis, where he is investigating aberrant gene-editing outcomes.

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Proteins are essential building blocks of life, but they can become toxic to our cells if damaged, for example under oxidative stress. In turn, human cells selectively remove damaged proteins to maintain a healthy proteome. But how can cells identify individual damaged proteins among thousands of intact ones? An old hypothesis states that cells scan the proteome for chemical modifications that occur, for example, when proteins break. Are you interested in learning more about how cells combat chemical protein damage?

Have a look at our newest research breakthrough, led by postdoc Matthias Muhar in a collaboration with Jakob Farnung from the Bode group (D-CHAB) as well as with Jessberger group (UZH), Jinek group (UZH), Mann group (Max Plank Institute of Biochemistry) Germany   and Schulman group (Max Plank Institute of Biochemistry, Germany).

In this study, using a semi-synthetic chemical biology approach coupled to cellular assays, we found that C-terminal amide-bearing proteins (CTAPs) are rapidly cleared from human cells.

To identify the cellular machinery underlying CTAP clearance, we utilized a genome-wide CRISPR screen for genes that are responsible for specific degradation of C-terminally amidated proteins. We identified SCF–FBXO31 ubiquitin ligase as a key reader of C-terminal amides, marking CTAPs for proteasomal degradation. With a conserved binding pocket, FBXO31 exhibits remarkable selectivity, binding C-terminal peptides with amides while excluding non-modified proteins. This mechanism allows cell to remove CTAPs, which form when proteins break under under oxidative stress. Intriguingly, a human mutation linked to neurodevelopmental disorders alters FBXO31’s substrate recognition, leading to toxicity. These findings suggest CTAPs may represent a new class of modified amino acid degrons (MAADs) that mark proteins for removal by reader proteins and downstream effectors, offering insights into selective surveillance of chemically damaged proteins.

In conclusion, this research uncovered new signals for protein clearance and advanced our understanding of cellular protein quality control.

For more info check out our new paper in Nature!

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We are thrilled to announce that GEML has been awarded an ETH grant to advance its pioneering research into the biological mechanisms driving phenotypic variability in human genetics. This project explores how cells respond to various genetic manipulations and how these adaptations influence phenotypic outcomes. By unraveling these processes, we aim to uncover key factors that shape disease traits and open new avenues for therapeutic intervention. This achievement highlights GEML’s leadership in cutting-edge genome engineering and our commitment to translating knowledge into transformative breakthroughs in human health. Stay tuned for updates on this impactful research!

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We’re happy to announce that Charles and Lilly received the BRIDGE Discovery supporting HT-DISCOVER, an exciting new technology for detecting genome editing off-targets. HT-DISCOVER is a drop-in technology that works even in established genome editing workflows, enabling safer and more effective therapies. With the support of BRIDGE Discovery, Charles and Lilly will bring this innovative technology to market in a future spin-off.

Stay tuned for more information!

For potential collaborations and partnerships involving HT-DISCOVER, please contact Jacob Corn (jacob.corn@biol.ethz.ch) and Lilly van de Venn (lilly.vandevenn@biol.ethz.ch).

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We’re thrilled to announce that Lilly has received the prestigious ETH Pioneer Fellowship! This achievement will empower her to transform her research-based technology into innovative product/service, paving the way for the launch of her spin-off, HT-DISCOVER. Her work will focus on advancing accurate and high-throughput off-target detection, ensuring precision and safety in genome engineering. 

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Genome editing creates double-strand breaks (DSBs) that can be repaired through either non-homologous end joining (NHEJ), microhomology-mediated end joining or homology-directed repair (HDR). While NHEJ is quick but error-prone, HDR uses a DNA template for precise edits, allowing targeted changes from single-nucleotide fixes to large gene insertions, greatly benefiting biomedical research and therapies. However, HDR is a relatively inefficient process, and ongoing efforts aim to improve its efficiency, including the use of small molecule inhibitors targeting DNA repair. One such highly potent inhibitor, AZD7648, selectively targets DNA-PKcs, redirecting DNA repair from the error-prone NHEJ pathway to the more precise HDR pathway in both transformed cell lines and primary human cells. However, the potential unintended consequences of its use in genome editing remain largely unexplored.

Are you curious to find out more?

Check out our recent advancement, led by postdoc Grégoire Cullot in a collaboration with the Gehart group (IMHS), Cathomen group (University of Freiburg, Germany) and the Gene Therapy research group of CSL Behring.

This work demonstrated that genome editing with a single Cas9-induced DSB in combination with AZD7648 leads to an increase in HDR, but this was accompanied by Cas9-induced genomic instability at on-target sites, where small-scale NHEJ outcomes were transformed into larger genetic alterations that cannot be detected by short-read sequencing.

Through the use of long-read sequencing, droplet digital PCR (ddPCR) for copy number analysis, single-cell RNA sequencing, and unbiased translocation detection, we discovered that AZD7648 significantly amplifies the frequency of kilobase-scale deletions, chromosome arm loss, and translocations across various cell types.

More broadly, genome editing-induced large-scale genomic alterations might still be largely underestimated. Indeed, these large-scale genomic alterations evade classical genome editing detection assays, typically short-read next-generation sequencing (NGS) and necessitate specific techniques that are not currently commonly used in the genome editing field. This means that clinical genome editing groups might be unaware of potential induced genomic instability and safety risks. Of note, AZD7648 is being tested by many clinical genome editing groups, however our results urge caution when deploying it during genome editing and reinforce the need to investigate genetic outcomes beyond those accessible to short-read target amplicon next-generation sequencing.

For more info check out our new paper in Nature Biotechnology!

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Tijana Nikic received her MSc in Human Biology from LMU Munich, completing her thesis in 2022 with Prof. Dr. Stefan Stricker on understanding astrocyte cell identity and optimizing their reprogramming to neurons. Tijana joined the Corn Lab as a PhD student to investigate the mechanisms of organelle clearance during reticulocyte maturation. Her research interests include functional genomics, unraveling molecular mechanisms driving cellular processes, and advancing genome editing technologies for therapeutic applications.

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We are thrilled to announce that Lilly has successfully defended her PhD! Her research focused on monitoring genome editing by visualizing DNA repair. She developed a high-throughput off-target identification method, enabling tracking of off-targets for thousands of human guide RNAs. A huge congratulations, Dr. van den Venn!

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