Lab News

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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NSF Graduate Fellow Emily Lingeman et al. have published a chapter “Production of Purified CasRNPs for Efficacious Genome Editing” in Current Protocols in Molecular Biology. This article describes how to make a Cas9 RNP and outlines its use for gene editing in human cells. Check it out if you’d like to get started with RNP-based gene editing.

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IGI Scientific Director of Biomedicine Jacob Corn has received the NIH Director’s New Innovator Award that provides $1.5 million over five years to pursue high-risk, high-reward work that could have implications for human health. The National Institutes of Health’s (NIH) High-Risk, High-Reward Research program, part of the NIH Common Fund, funded 86 awards to exceptionally creative scientists proposing to use highly innovative approaches to tackle major challenges in biomedical research.

Corn lab will use CRISPR-Cas9 gene editing to explore how cells recycle damaged organs, such as mitochondria. Dysfunction in organelle autophagy has been implicated in diverse diseases, including neurodegeneration, lysosomal storage disorders and cancer.  Corn lab will use next- generation CRISPR-Cas9 genome editing and regulation technologies, combined with cellular biochemistry and imaging to discover the pathways that signal for the remodeling and lysosomal degradation of multiple organelles.  Our work will reveal the mechanisms by which cells maintain organelle homeostasis and respond to organelle damage or stress, which could suggest new strategies to treat diseases associated with improper organelle autophagy.

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The work of IGI scientists “Discovery of stimulation-responsive immune enhancers with CRISPR activation” was recently published in Nature. The researchers used CRISPR activation to find DNA “switches” that control key genes in the immune response and autoimmune disease. Post-doc Benjamin Gowen and PhD student Dimitre Simeonov were the lead authors. IGI Scientific Director Jacob Corn and IGI affiliate Alexander Marson jointly supervised the work. Important contributions were made by several Corn Lab members and alumni, including Mandy Boontanrart, Nicolas Bray, Therese Mitros, Jordan Ray, Gemma Curie, Nicki Naddaf, Julia Chu, and Hong Ma.  A summary of the research was featured by the UCSF News Center.

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A series of interviews and lab visits by The Daily Californian show what it’s like to work inside some of UC Berkeley’s most high-level labs.  Our lab is featured in the article “The Genome Revolution: Inside UC Berkeley’s CRISPR labs” .  

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