Lab News

MCL1/CDK9 screen published in eLife

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!

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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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We’re hiring!

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...

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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

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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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Papers!

The Corn lab has been a frenzy of activity in preparation for the move to ETH Zurich. We missed posting news of several publications at the time they happened,...

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The Corn lab has been a frenzy of activity in preparation for the move to ETH Zurich. We missed posting news of several publications at the time they happened, so here’s a big post to get us up to date. Many thanks to our wonderful collaborators and congratulations to everyone involved in these awesome pieces of research!

In reverse chronological order:

Elena Zelin
BARD1 is necessary for ubiquitylation of nucleosomal histone H2A and for transcriptional regulation of estrogen metabolism genes.
This paper was a fun collaboration with the lab of Rachel Klevit. BRCA1 gets a lot of press, but does its binding partner matter just as much? Our contribution was to use genome editing to make several BARD1 mutant MCF10A clones and determine how they affected regulation of BRCA1/BARD1 target genes.

Jiyung (Jenny) Shin
Enhanced genome editing with Cas9 ribonucleoprotein in diverse cells and organisms.
Want a hands-on introduction to using the Cas9 RNP, complete with high-quality video how-tos? Then check this one out! This paper was organized by Megan Hochstrasser, the outstanding IGI communications director, and is a collaboration with the labs of Alex Marson, Barbara Meyer, and Nipam Patel.

Beeke Weinert, Jenny Shin, and Elena Zelin
In vitro-transcribed guide RNAs trigger an innate immune response via the RIG-I pathway. 
When using the Cas9 RNP for editing, it’s fast, cheap, and easy to use IVT to make guide RNAs. We’ve written a widely-used protocol on making guide RNAs in very high throughput. But it turns out that leaving the 3′ triphosphate on these guide RNAs can make primary cells freak out due to innate immune sensing. Read this paper to find out a quick fix (beyond using synthetic guide RNAs). This was a collaboration with Kathleen Pestal.

Chris Richardson, Katelynn Kazane, Elena Zelin, Nick Bray
CRISPR-Cas9 genome editing in human cells occurs via the Fanconi anemia pathway.
How does genome editing even work? Cas9 and other Cas proteins just make breaks in genomes. Everything else is up to the cell. This paper uses a new screening approach to simultaneously test thousands of genes for their involvement in genome editing. Surprisingly, the Fanconi Anemia crosslink repair pathway is critically important for HDR from a single stranded DNA donor. This was a fun collaboration with Stephen Floor.

Amos Liang, Emiy Lingeman, Saba Ahmed
Atlastins remodel the endoplasmic reticulum for selective autophagy.
Cells can eat their own organelles via autophagy, and even somehow take apart the endoplasmic reticulum and package it into lysosomes. This manuscript develops several highly sensitive and quantitative reporters for ER-autophagy. Using these, we find that ER-resident proteins called atlastins are required for ER remodeling during ER-autophagy. Human mutations in atlastins cause paraplegias that are very similar to the phenotypes of mice with mutations in other known ER-autophagy proteins. Paraplegias may be a common outcome of defects in ER-autophagy, much as Parkinson’s Disease is a common outcome of defects in mitochondrial-autophagy.

 

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End of the year for our fabulous undergrads

The semester is over, and our undergrads gave stellar presentations over three packed days of Corn Lab Undergradapalooza. Many of the lab undergrads are graduating,...

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The semester is over, and our undergrads gave stellar presentations over three packed days of Corn Lab Undergradapalooza. Many of the lab undergrads are graduating, which is bittersweet. It’s great to see them doing well, but sad to see them go. Farewell to Saba Ahmed, Leo Chen, Jennifer Chung, Sharon Feng, Rachel Lew, Tracie Luong, Shirley Shao, and Ankita Singh. Wishing you all the very best for each and every one of your future endeavors.

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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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