Lab News

Welcome to Dora!

Dora obtained her Master’s degree in Chemistry from ETH Zurich in 2019, where she conducted research on the Synthesis of trypanothione reductase inhibitors...

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Dora obtained her Master’s degree in Chemistry from ETH Zurich in 2019, where she conducted research on the Synthesis of trypanothione reductase inhibitors in the Diederich group (Chem. Eur. J., 2019) and Templated length-controlled oligomerization in the Wennemers group (Faraday Discuss., 2023). In May 2025, Dora joined the Corn Lab as a PhD student to investigate how cells sense and respond to genetic perturbations. Her research focuses on uncovering how transcriptional adaptation shapes phenotypic variability and contributes to disease-relevant traits.

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Welcome back to Dominic!

Dominic Mailänder received his Master’s degree in Molecular Health Sciences from ETH Zurich in 2024. Dominic returned to the Corn Lab as a Research ...

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Dominic Mailänder received his Master’s degree in Molecular Health Sciences from ETH Zurich in 2024. Dominic returned to the Corn Lab as a Research Technician in April 2025. His current work centers on the development and automation of a high-throughput CRISPR off-target detection protocol.

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SYNTHETIC LETHALITY IN DNA DAMAGE RESPONSE- PUBLISHED IN NATURE

The DNA damage response (DDR) protects the genome from myriad insults. Indeed, because endogenous damage is an existential and continual threat, cells achieve...

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The DNA damage response (DDR) protects the genome from myriad insults. Indeed, because endogenous damage is an existential and continual threat, cells achieve robustness by engaging multiple overlapping pathways to deal with it. In the context of cancer, these relationships can present therapeutic opportunities because DDR-deficient tumors often rely on backup repair mechanisms for survival. However, addressing this complexity is a daunting challenge because gene functions in essential DNA repair processes can be masked and overlooked when pathways use completely different mechanisms to complement one another. But which DDR gene interactions are essential for cell survival during normal homeostasis? Our latest CRISPR interference (CRISPRi) screen has the answers!

In our latest paper, we performed the most systematic genetic interaction investigation of the human DDR to date. This exciting new work was driven by postdoc John Fielden and PhD student Sebastian Siegner in collaboration with the Jackson  (UCAM), Cejka (USI) and Jost  (HMS) labs.

We tested 150,000 genetic interactions, asking which DDR genes have synthetic lethal interactions with each other. We uncovered previously unknown connections between DNA repair factors as well as interactions that may be clinically exploitable. All these interactions can be browsed on our user-friendly website, SPIDRweb.

 For deep mechanistic studies, we prioritized two of the strongest novel synthetic interactions: WDR48:LIG1/FEN1 and FANCM:SMARCAL1. First, we found that WDR48 partners with USP1 to prevent PCNA degradation in cells lacking either FEN1 or LIG1, two enzymes which ordinarily prevent the accumulation of DNA nicks, gaps, and single-strand breaks. Second, we revealed that FANCM and SMARCAL1, two well-known but previously unconnected DNA translocases, have overlapping roles in unwinding DNA secondary structures that form at TA-rich repeats. In doing so, they effectively shield the genome from catastrophic fragmentation by the ERCC1-ERCC4 nuclease complex.

From a clinical perspective, our data suggest that already existing USP1 inhibitors may synergize with chemotherapies that induce DNA gaps, such as ATR and WEE1 inhibitors. Moreover, FANCM and SMARCAL1 are mutated in breast cancers and glioblastomas, respectively, pinpointing them as promising targets for drug development.

Overall, our work reveals new aspects of DDR biology and suggests multiple targets for synthetic lethality-based cancer therapy. We anticipate that our genetic interaction map will reveal further insights into fundamental DDR biology as well as cancer cell-specific vulnerabilities and candidate drug targets.

For more info check out our new paper in Nature!

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Welcome to Rafaela!

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...

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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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Welcome to Boris!

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...

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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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C-TERMINAL AMIDES FUNCTION AS SIGNALS FOR PROTEIN DEGRADATION- PUBLISHED IN NATURE

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 ...

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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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Congratulations to Zac who was awarded an ETH grant!

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...

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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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Congratulations to Charles and Lilly on the BRIDGE Discovery grant!

We’re happy to announce that Charles and Lilly received the BRIDGE Discovery supporting HT-DISCOVER, an exciting new technology for detecting genome...

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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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Happy Holidays!

We wish you a joyful holiday season and a Happy New Year! Special thanks to Martina and Jenna for creating this amazing card! Cheers!

Congratulations to Lilly on the ETH Pioneer Fellowship!

We’re thrilled to announce that Lilly has received the prestigious ETH Pioneer Fellowship! This achievement will empower her to transform her research-based...

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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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Questions and/or comments about Corn Lab and its activities may be addressed to:

JACOB.CORN@BIOL.ETHZ.CH

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