Lab News

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 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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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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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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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!

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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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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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Chris Richardson joined the lab as a Postdoctoral Fellow in July 2014 and made huge advances in human gene editing. He developed new ways to improve NHEJ and HDR, plus discovered out that genome editing in human cells works via the Fanconi Anemia Pathway. Three major first author papers in three years – not bad! Chris will be joining Spotlight Therapeutics as a Group Leader, and may have some additional career news to share soon. We wish you success in all your future endeavors!

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Not your typical news post! The Corn Lab will be moving to the ETH in Zurich, Switzerland. Jacob is accepting a position as a full professor in the Institute for Molecular Health Sciences. The IGI and UC Berkeley MCB have been wonderful places to do research and work to make an impact on genetic disease. It’s hard to believe that it’s only been 4 years since Jacob moved from Genentech to help start up IGI. And reflecting back, it’s wild to see how much IGI has grown! What a great time!

We’ll be fully moved in October of 2018. The main thrust of my research program won’t change, so get in touch if you’re interested in a Ph.D. or postdoc in working on gene editing, DNA repair, hematopoietic stem cell biology, or organelle autophagy. I’m looking forward to new friends and colleagues, and to having current friends and colleagues come visit the Alps!

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Benjamin Gowen joined our lab as a Postdoctoral Fellow in May 2015 and used the CRISPR/Cas9 system to study T cell regulation. Congratulations on his big step in becoming the Co-Founder and CEO at Peregrine Biotechnology, Inc. Wishing you much luck on your new business venture.

Hong Ma joined the lab as a Research Associate I in February 2016. She has accepted a Research Associate II position in Kramer Lab. Best wishes as you embark on a new challenge.

Rachel Valenzuela joined the IGI staff as a Postdoctoral Fellow in July 2016, and used the CRISPR/Cas9 system to study the factors involved in metabolic disorders in human and mouse models. She will be a Cell Line Engineer at Memphis Meats. Best of luck in your new job!

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