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CRISPR in Mycobacterium Tuberculosis Rocks the Boat a U Dr E Y G Ol Dfa R B

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CRISPR in Mycobacterium Tuberculosis Rocks the Boat a U Dr E Y G Ol Dfa R B Issue 165 December 2019/January 2020 A NEWSLETTER OF THE ROCKEFELLER UNIVERSITY COMMUNITY CRISPR In Mycobacterium Tuberculosis Rocks the Boat A UDREY G OLDFA RB Dr. Jeremy Rock heads the Labora- tory of Host-Pathogen Biology located on the south side of the River Campus Re- search Building. Rock studies Mycobacte- rium tuberculosis (Mtb), a bacterium that exclusively parasitizes humans. Tuberculo- sis (TB) is the leading cause of death from infectious disease, but Mtb biology is still poorly understood. Rock pursued his interest in Mtb after completing his Ph.D. at the Massachusetts Institute of Technology working with yeast, the exhaustively characterized workhorse of genetics. “I did a Ph.D. in yeast genetics, and I loved it,” Rock said. “The rigor and depth with which you can answer a question in this model organism is second to none. But I wanted to move to an area that was more di- rectly medically relevant, and in which there was a lot of big, unanswered questions.” Immediately, there were challenges. Photo Courtesy of TONY RINALDO Yeast doubles once every ninety minutes, and E. coli every twenty. To the disadvan- a lot of very interesting hits, and we’re now people I spend a lot of time with, and they’re tage of Rock and his colleagues, Mtb’s dou- trying to figure out the biology. This is what all people I love being around.” bling time is a full twenty-four hours. “It we wanted to do with it, and it’s actually was not a painless transition,” Rock said. working.” The lab’s productivity is due in large “Everything grows faster than TB. So, if you Using CRISPR guides of different part to the bioinformatics expertise of com- don’t have sterile technique everything gets strengths, Rock is able to knock down es- puter scientist Dr. Michael DeJesus. “He’s contaminated.” sential genes to varying degrees. This ranks just phenomenal,” Rock said. “The math Rock wanted to identify essential essential genes by their vulnerability: even behind what we’re doing pretty quickly got genes in Mtb using CRISPR in order to re- slight knockdown of some genes in Mtb is complicated to the point where we needed veal potential therapeutic targets. However, lethal, while others require more robust de- someone like him. He was the perfect per- the traditional CRISPR systems used in oth- pletion to kill the bacterium. If a gene prod- son to bring in.” er organisms did not seem to work in Mtb. It uct requires minimal inhibition to elicit a Developing CRISPR in Mtb was a took Rock two years of his postdoctoral fel- therapeutic benefit, it can more easily be huge hurdle with a huge payoff. “It was slow, lowship to identify the Cas9 allele that could targeted by drugs. it was hard, and it didn’t always work,” Rock edit the Mtb genome. Though the lab is less than two years said. “But it was clearly a problem that was His lab at Rockefeller is now able to old, Rock is already thrilled with the people important, and it was going to open a lot of identify hundreds of candidate genes from he has recruited. “They’re a very hard work- doors.” a single CRISPR screen. “We can do 100,000 ing, collegial bunch,” he said. “Everyone experiments at once,” Rock said. “We have collaborates and helps each other. These are CONTINUED TO P. 2 - 1 Editorial Board Sarah Baker Editor-in-Chief, Managing Editor, Webmaster Megan Elizabeth Kelley Associate Editor, Communication Emma Garst Associate Editor Evan Davis Copy Editor, Photographer-in-Residence Nicole Infarinato Editorial Assistant, Distribution Melissa Jarmel Copy Editor, Website Traffic Photo Courtesy of ALEXANDRA ROWLEY Pooja Viswanathan Copy Editor, Website Design CONTINUED FROM P. 2 - and structures may be on the horizon. “We like screening for genes that contribute to Audrey Goldfarb Rock also acknowledged the support interesting phenotypes, and now that we Anna Amelianchik he has received throughout his career, espe- have lots of hits we’re excited about and Jennifer Einstein cially as a new faculty member at Rockefell- zooming in on more mechanistic studies,” Copy Editors er. “When you start a lab, you have to build Rock said. it from the ground up,” Rock said. “But it’s Meaningful success in science is usu- Jim Keller not like you do that alone. Both junior and ally preceded by myriad failures, making Editor-at-Large senior faculty were very welcoming, and the hard work and persistence essential even Nan Pang administration is amazing. They really take for talented minds. “A lot of this job is just Designer care of you and help you in this process.” tenacity,” Rock said. “That goes a really long Rock is excited to pursue mechanistic way. In order to be tenacious, you have to selections.rockefeller.edu studies to nail down the detailed biology of really love your project. Science is never [email protected] Mtb. Collaborations to elucidate pathways easy, but you’ll figure it out.” n Natural Expressions Performance for more information and discounts on Digital Collete Ryder of The Rockefeller Uni- tickets. Bernie Langs of The Rockefeller Uni- versity’s Office of Sponsored Programs versity Development Office has re- Administration will be singing with On Saturday, December 14th at 7 p.m., leased a new music video, “How Can NYCHORAL on Friday, December 13th Lance Langston of the O’Donnell Labo- You Mend a Broken Heart.” In this lat- at 7:30 p.m. and Saturday, December ratory and Alison North of The Rockefell- est video, Langs performs music by 14th at 2:30 p.m. at Our Lady of Pompeii er University Bio-Imaging Resource Cen- the Bee Gees and Madonna, acting as Church (25 Carmine St.). The event, “Cel- ter will be singing with the Central City both musician and film director. Check ebration! A NYCHORAL Christmas,” fea- Chorus at St. Ignatius of Antioch Episco- out his video here on YouTube. tures Daniel Pinkham’s “Christmas Can- pal Church (552 West End Avenue). The tata,” John Rutter’s “Gloria,” Ola Gjeilo’s program features “Mid-Winter Songs” by “A Spotless Rose” and “The Rose,” Franz Morten Lauridsen, the New York premier Email Megan E. Kelley at mkelley@ Biebl’s “Ave Maria,” and an audience of “Lux Brumalis” by Nathaniel Adams, rockefeller.edu to submit your art/mu- sing-along. Children under 12 years old and other festive seasonal works. Tickets sic/performance/sporting/other event can receive reduced admission for the are $20 in advance ($25 at the door) and for next month’s “Natural Expressions” family matinee on Saturday. Contact can be purchased online at the Central and follow @NatSelections on Twitter Collette Ryder ([email protected]) City Chorus website. for more events. 2 Giving during the Season of Giving N ATA LI A K ETA RE N Fall has broken, the nights are getting Hope For New York can also drop your coat and shoes (and any chillier and the holiday season is fast ap- I’ve been volunteering with HFNY other clothes you may no longer need) di- proaching. For many of us, this is a time for for many years now. They are a non-de- rectly at The Bowery Mission, which is right family, giving, and quality time with loved nominational Christian organization that next door. Visit https://www.newyorkcares. ones. The words “Joy,” “Merry,” and “Spirit” are is affiliated with many charitable organiza- org/coat-drive and https://www.newmuse- in abundance. They are a reminder that with tions, offering support to our most vulner- um.org/pages/view/neighborhood for more this cold, wintery season approaching, we able neighbors here in NYC. Their mission information. shouldn’t be wintery inside. This holiday sea- is for NYC to be, “...a city in which all people For direct drop-offs at the Bowery son is steeped with virtuous traditions. At the experience spiritual, social, and economic Mission, visit 227 Bowery, New York, NY core of them all is a time of reflection, making flourishing through the demonstration of 10002 (open 24 hours) us thankful for the positive things that have Christ’s love.” Their website allows you to come our way. Often these moments of reflec- navigate through their many opportunities, God’s Love We Deliver tion encourage us to share our giving spirit to which range from educational support for Many of our sick neighbors in NYC our unseen neighbors here in New York City, low-income individuals, to assisting with find it difficult to afford healthy meal op- our neighbors in need. meal services for the needy. Visit https:// tions. “God’s Love We Deliver” cooks, pre- Here are a few suggestions to give to www.hfny.org/ for more information. pares, and delivers nutritious, medically those in need in NYC during this holiday sea- tailored meals for those too unwell to do so son: Coat Drives for themselves. You can donate on their site We all know the necessity of a warm or get involved directly by volunteering with New York Cares Winter Wishes coat during this holiday season. There are them. Visit https://www.glwd.org/ for more In NYC every year, one in ten NYC stu- many places in the city to donate a gently information. dents experience homelessness. The “Winter used coat you’ve lost need of. New York Wishes” program run by New York City Cares Cares has an annual coat drive with many These are just a few ways to give this is a holiday gift drive aimed at providing gifts drop off location throughout the city.
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