Lab News

Welcome to Lena

Welcome to Lena Kobel, who joins the lab as a Cell Line Engineer. Lena has a long history in genome engineering, with previous experience in Martin Jinek’s lab...

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Welcome to Lena Kobel, who joins the lab as a Cell Line Engineer. Lena has a long history in genome engineering, with previous experience in Martin Jinek’s lab and at Caribou Biosciences. Lena will be working on precision cell models and screens to study the genetics of DNA damage and genome editing.

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ER-autophagy screen published in Cell

Did you know that cells eat their own organelles? This is best known when damaged mitochondria are degraded by autophagy (aka mitophagy). Failure to perform...

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Did you know that cells eat their own organelles? This is best known when damaged mitochondria are degraded by autophagy (aka mitophagy). Failure to perform mitophagy can lead to diseases such as Parkinson’s. But many other organelles are also degraded by autophagy. We have been studying autophagy of the endoplasmic reticulum (ER-phagy), which is much less understood than mitophagy. Engulfing a mitochondria in an autophagosome sounds pretty straightforward, but ends up being complicated. Now imagine needing to do that for one part of the ER network! A handful of direct ER-phagy receptors are known. But these receptors are always on the ER, so it was not clear what really initiates and controls ER-phagy. How does the cell know what part to engulf? What are the signals that turn this on and off? What happens when it goes wrong?

Superstars Amos Liang (postdoc) and Emily Lingeman (PhD student) tackled this question in a big way. Using a highly sensitive fluorescent reporter for ER-phagy, they used CRISPRi to ask what genes regulate ER-phagy. The first surprise was that intact mitochondrial oxidative phosphorylation is required to successfully initiate ER-phagy. This is odd because preventing oxidative phosphorylation actually initiates bulk autophagy. But the opposite is true for ER-phagy! The second big surprise was that a weird post-translational modification called UFMylation is required for ER-phagy. Lots of mechanistic work showed how UFMylation machinery is brought to the ER surface and what gets UFMylated during ER-phagy. There are some very interesting parallels to mitophagy, but using totally different machinery. Third, many of the genes involved in ER-phagy are involved in peripheral neuropathy in humans. Since their role in ER-phagy wasn’t previously known, it wasn’t understood how they were connected to cause human disease. This work suggests that failure to do ER-phagy links them all and leads to neurodegeneration. There’s a lot going on here, so read the paper to find out more.  Congrats to Amos and Emily!

 

 

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Choosing the right path in genome editing – review published in Nature Cell Biology

Genome editing is all about DNA repair. So if you want to get your cells to do more of what you want (*cough* HDR *cough), you’d better know how they make ...

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Genome editing is all about DNA repair. So if you want to get your cells to do more of what you want (*cough* HDR *cough), you’d better know how they make decisions about DNA repair pathways. To help people get the lay of the land, Ph.D. student Charles Yeh and former postdoc Chris Richardson wrote a review all about manipulating DNA repair decisions to influence genome editing outcomes. Out now in Nature Cell Biology!

Be sure to check out Table 1 for a very thorough, non-redundant summary of all the ways people have tried to redirect CRISPR-Cas repair in human cells!

 

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CDN transporter collaboration with David Raulet published in Nature

Cells have many ways to figure out that something is wrong. One of these is cGAS, which makes a cyclic dinucleotide (CDN) to activate STING innate immune signaling....

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Cells have many ways to figure out that something is wrong. One of these is cGAS, which makes a cyclic dinucleotide (CDN) to activate STING innate immune signaling. CDNs are made during bacterial infection and tumor progression, and CDN derivatives are in development to re-activate immune cells next to a tumor. But how do CDNs secreted into the environment get into a target cell? This was the question asked by David Raulet’s lab, who collaborated with us on a genome-wide CRISPRi screen to find the CDN transporter. We helped the Raulet lab identify the folate transporter (SLC19A1) as a CDN importer. The Raulet lab plus further collaboration with Joshua Woodward’s lab figured out the mechanism. Lingyin Li’s lab also identified the folate transporter in a parallel collaboration with Mike Bassik, reported in Molecular Cell. Congrats to former lab members Benjamin Gowen and Stacia Wyman, who were authors on the paper, now out in Nature!

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Welcome to Zac

Welcome to Zac Kontarakis, who is the head of the new Genome Engineering and Measurement Lab (GEML). The GEML is a new hub, jointly developed by Jacob Corn and...

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Welcome to Zac Kontarakis, who is the head of the new Genome Engineering and Measurement Lab (GEML). The GEML is a new hub, jointly developed by Jacob Corn and the Functional Genomics Center Zurich, that will focus on the development of innovative approaches to genome engineering and their deployment to the Zurich research community. You may know Zac’s work already from his mind-blowing papers on mechanisms of genetic compensation. Stay tuned for more from Zac and the GEML!

 

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Welcome Erman, Kinga, and Markus

From left to right: Markus, Kinga, and Erman

Three people joined the lab, all in one day! Erman is a postdoc, interested in DNA repair and genome editing, Kinga...

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From left to right: Markus, Kinga, and Erman

Three people joined the lab, all in one day! Erman is a postdoc, interested in DNA repair and genome editing, Kinga is our new lab manager, and will be keeping us all in line. Markus is a bioinformatician, working on quantifying editing outcomes from complex datasets. Welcome to the lab!

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DISCOVER-seq published in Science

The lab’s manuscript on DISCOVER-seq is out today in Science. DISCOVER-seq is a way to watch Cas enzymes doing their things in any cell, or even an organism....

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The lab’s manuscript on DISCOVER-seq is out today in Science. DISCOVER-seq is a way to watch Cas enzymes doing their things in any cell, or even an organism. It uses recruitment of DNA repair factors to find off-targets and provides single-nucleotide resolution of Cas repair dynamics. Congrats to co-first authors Beeke Weinert and Stacia Wyman! And thanks to our wonderful collaborators in the Conklin labs and at AstraZeneca.

Want to give DISCOVER-seq a try? There is a very detailed protocol on protocols.io and code on Github.Feel free to reach out if you’re having trouble or want to collaborate.

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Charles passes his qual!

Charles moved all the way from Berkeley to Zurich with the Corn Lab. If he had stayed at Berkeley, he would have taken a qualifying exam. Things are a bit different

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Charles moved all the way from Berkeley to Zurich with the Corn Lab. If he had stayed at Berkeley, he would have taken a qualifying exam. Things are a bit different across the pond, but there’s still a milestone at the end of the 2nd year of grad school. Charles passed with flying colors and had the honor of wearing the traditional Corn Costume.

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Welcome to our new Ph.D. students

We have two new Ph.D. students at ETH Zurich: Marija Banovic and Lilly van de Venn. Marija is interested in the biology of hematopoietic stem/progenitor cells...

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We have two new Ph.D. students at ETH Zurich: Marija Banovic and Lilly van de Venn. Marija is interested in the biology of hematopoietic stem/progenitor cells and translational research with the special emphasis on the implementation of genome editing technologies for therapeutic purposes. Lilly’s interests include DNA repair mechanisms, as well as the potential use of genome editing for therapeutic purposes. Welcome!

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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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