Lab News

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!

X Close

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!

X Close

Our CRISPR screening projects are starting to come out! Today work from postdoc Shaheen Kabir, in collaboration with oncologists at AstraZeneca, was published in eLife. Shaheen used a very creative FACS screen to find genes involved in the early apoptotic response to CDK9 and MCL1 inhibitors. Inhibition of CDK9 reduces transcript half-life and indirectly inhibits MCL1, whereas the other compound screen directly binds MCL1. Several cancers respond well to these new compounds, but others are already completely resistant. Shaheen went looking for genes involved in this resistance and found some very interesting shared hits. She focused her mechanistic work on the CUL5 ubiquitin ligase complex, which is a multi-component system used to degrade target proteins. Almost every component of the CUL5 complex was a hit in the screen, and Shaheen found that knockdown of CUL5 components affected the stability of pro-apoptotic proteins Bim and Noxa. CUL3 type ligases are already established cancer targets, and Shaheen’s work shows that CUL5 could also be targeted to synergize with front-line cancer therapeutics. Congratulations Shaheen!

X Close

Matthias is a new postdoc in the lab, having joined after completing his Ph.D. with Johannes Zuber at the IMP in Vienna. Welcome!

X Close

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!

X Close

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.

X Close

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.

X Close

Are you interested in working on genome editing, DNA repair, and organelle quality control in a dynamic lab environment? We are seeking a technician/lab manager and a bioinformatics scientist. Apply at the links below.

Technician / Lab Manager

Bioinformatics Scientist

X Close

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!

X Close

We had an slightly belated American Thanksgiving in Zürich, complete with turkey, stuffing, mashed potatoes, and gravy. After eating more than our fill, we all walked down to a big Weinachtsmarkt for Glühwein. A great start to the holiday season!

X Close