CONTENTS NEWS FEATURES PERSPECTIVES 2 14 22 PRESIDENT’S MESSAGE QUANTUM BIOLOGY COORDINATES CONTINUES TO INTRIGUE Exiting the hobbit hole 5 10 NEWS FROM THE HILL 24 What’s on tap for 2016 MINORITY AFFAIRS 24 Research spotlight 6 26 Committee update MEMBER UPDATE 28 8 EDUCATION NEWS Why should you be an ASBMB 8 NIH retiring 50 reserve chimpanzees Student Chapters adviser? 9 Proteins get their own periodic table 12 30 10 CAREER INSIGHTS JOURNAL NEWS Working at a PUI 10 Implicating proteins in synaptic plasticity 11 When the good and the bad make the ugly 24 12 JLR co-editor in chief steps down 13 e details of DNA end resection 7 14 Rajendrani Mukhopadhyay on the comeback of quantum mechanics in molecular biology. 22 JANUARY 2016 ASBMB TODAY 1 PRESIDENT’S MESSAGE THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY PCP addict By Steven McKnight OFFICERS COUNCIL MEMBERS Steven McKnight Squire J. Booker President Karen G. Fleming Gregory Gatto Jr. o — I’m not talking about Were it up to me — and as I have Natalie Ahn Rachel Green phencyclidine or angel dust but admitted over and over, it is not — I President-Elect Susan Marqusee instead PCP as an abbreviation would never fund a research project Jared Rutter N Karen Allen Secretary Brenda Schulman for three words: phenomenon, curios- that did not do one of two things. A Michael Summers ity and paradox. worthy project should either question Toni Antalis Treasurer ASBMB TODAY EDITORIAL My 1973 edition of Webster’s our existing assumptions or propose ADVISORY BOARD New Collegiate Dictionary denes a an uncharted pathway directed toward EX-OFFICIO MEMBERS Charles Brenner phenomenon as “a rare or signicant an unexplained biological phenom- Squire Booker Chair fact or event,” a curiosity as “one enon. Wei Yang Michael Bradley Co-chairs, 2016 Annual Floyd “Ski” Chilton that arouses interest especially for Knowing that my advice is anti- Meeting Program Cristy Gelling uncommon or exotic characteristics,” thetical to the status quo, I start with Committee Peter J. Kennelly and a paradox as “a tenet contrary to the truth-in-advertising warning that Rajini Rao Peter J. Kennelly received opinion.” I’m always on the the thoughts presented herein are Chair, Education and Yolanda Sanchez Professional Development Shiladitya Sengupta lookout for any PCP worthy of study. anti-professional. Follow this advice, Committee Carol Shoulders Once I nd a good one, I see the and you are almost certain to get your Daniel Raben opportunity to make a discovery. grant application triaged. Chair, Meetings Committee ASBMB TODAY Angela Hopp Before discussing ways of nding PCPs abound in biology. ey hit Takita Felder Sumter Executive Editor, Chair, Minority Aairs PCPs, let’s rst question the value of us in the face without even looking for [email protected] Committee this strategy. them. Some may defy conventional Lauren Dockett omas Baldwin Managing Editor, With respect to practicality wisdom and be paradoxical, others Chair, Outreach Committee [email protected] (careerism), this approach is a bad may constitute little more than weird Wes Sundquist Rajendrani Mukhopadhyay idea. Committing to a project that is curiosities, and still others may rest Chair, Public Aairs Chief Science Correspondent, Advisory Committee [email protected] unusual, exotic or contrary to opinion on a newly observed phenomenon of Blake Hill Valery Masterson is not easy. Granting agencies tend to interest. Chair, Publications Designer, choke on ideas that are new, dier- I bump into PCPs on a regular Committee [email protected] Lauri Pantos ent or a challenge to conventional basis. Here are several examples that F. Peter Guengerich Manager of Publications wisdom. ey want us to add incre- I thought of without getting up from Interim editor-in-chief, JBC Technology, [email protected] mentally to the existing knowledge my chair. Herbert Tabor Ciarán Finn Co-editor, JBC Web Publication Assistant, base; they want to know that what Starting with the phenomenon [email protected] A. L. Burlingame we propose in our grant applications category of the PCP triad, I recount a Editor, MCP Allison Frick Media Specialist, will work. Nothing I’ve ever known conversation I had recently with my Edward A. Dennis [email protected] for sure will work and proceeded to colleague, Betsy Goldsmith. Betsy William L. Smith Barbara Gordon do has added anything of signicance. is interested in how cells respond to Co-editors, JLR Executive Director, [email protected] If a project is perceived as likely to changes in osmotic pressure. Much to succeed, building on what already is her surprise, Betsy found an enzyme known and accepted, it is far more that is pressure sensitive and involved For information on advertising, contact Pharmaceutical Media Inc. at 212-904-0374 or [email protected]. digestible to most review committees in a signaling cascade that responds than a project seeking to challenge to extracellular osmolarity. How crazy dogma or break new ground. and cool is this? An enzyme that is www.asbmb.org/asbmbtoday PRINT ISSN 2372-0409 Correction Articles published in ASBMB Today reect solely the authors’ views and not the ocial positions of e article “More good news about aspirin” in the October 2015 issue of the American Society for Biochemistry and Molecular ASBMB Today incorrectly referred to salicylate as an acetylated form of Biology or the institutions with which the authors are aliated. Mentions of products or services are aspirin. It is an unacetylated form of aspirin. not endorsements. ©2015 ASBMB 2 ASBMB TODAY JANUARY 2016 pressure sensitive! Betsy sticks her the ultraconserved intronic elements technical hurdles might be way too enzyme in a test tube, pumps up the of the NPAS3 genes as to its protein- high, or our instincts may simply be pressure, and the enzyme activates coding exons. is is a curiosity. dead wrong. magically. Talk about a cool phenom- I’ll close with a paradox. Several PCP projects are risky. We all know enon! years ago, my trainees and I stumbled this. What if our system of grant fund- Moving to the curiosity category, I onto the fact that low-complexity ing, instead of betting on sure winners turn to a gene my lab has studied for a sequences associated with many DNA guaranteed of incremental advance, while — the gene encoding a tran- and RNA regulatory proteins can instead demanded that each funded scription factor that we call neuronal polymerize into amyloidlike bers. project aim at a unique phenomenon, PAS domain protein 3, or NPAS3. Intuition and certain experimental curiosity or paradox? A small fraction e NPAS3 gene has ridiculously large observations led us to hypothesize that of the annual budget of the National introns. Two of the introns span nearly there might be biologic utility to LC Institutes of Health is indeed devoted a million base pairs. Geez, it takes the sequence polymerization. Whether to high-risk, high-reward projects — RNA polymerase II enzyme ve to 10 we are right or wrong on this remains perhaps 1 percent in aggregate. Why hours simply to transcribe the gene open to question. e paradox that is do we not devote a higher fraction of from end to end. Other genes are big, clear, however, is that the amyloidlike biomedical research funding to crazy so the whalelike size of NPAS3 introns bers polymerized from LC sequences exploration? is not all that perplexing. Cool and are labile. is is crazy. As visualized e success rate of PCP-funded unexpected is the fact that the introns by electron microscopy, LC amyloids projects would be modest. Many of the NPAS3 gene contain hundreds look just like pathogenic amyloids that would fail. By contrast, the small of ultraconserved elements 100 to 300 are rock solid and at the heart of many number of wins might accelerate base pairs in length. ese elements forms of neurodegenerative disease. our understanding of how biological have been conserved for upward of How can two amyloid bers look the systems actually work. e careers half a billion years, going back to the same yet be entirely dierent with of scientists crazy enough to expend evolutionary time when our ancestors respect to lability? their shot on the goal of a four-year diverged from teleost sh. I happen to believe that these three period of grant funding on a wild and e intronic sequences of the PCPs are pregnant with discovery. crazy project might well decay and die NPAS3 gene are conserved to an at is the good news, and that is on the journey. Despite this risk, I’m extent equal to the handful of exons what causes me to adore my job. e thinking that the line for those bold that encode the polypeptide sequence bad news is that I can’t be sure that enough to give PCP a try might be of the NPAS3 protein. If we knew studies of Betsy’s pressure-sensitive long. nothing about exons, introns, proteins enzyme, the ultraconserved intronic — nothing about the central dogma elements of the NPAS3 gene or our Steven McKnight (steven. of molecular biology — yet were able labile amyloids will illuminate our [email protected]) is president of the American to sequence and comparatively align understanding of biology. Instincts tell Society for Biochemistry and the NPAS3 genes from dozens of me they will, but these are the sorts of Molecular Biology and chairman vertebrates, evolution would be telling projects that most grant review groups of the biochemistry department at the University us to pay just as much attention to would automatically reject — the of Texas-Southwestern Medical Center at Dallas. JANUARY 2016 ASBMB TODAY 3 Submit Your Next Paper to an ASBMB Journal! When you submit a paper to an ASBMB ASBMB journal special features: journal, you can expect: • Customized eTOC alerts • Thorough, constructive reviews by scientists • Explore the Editorial Board • Affordable publication charges (*FREE color) • Meet new Associate Editors • Peer reviewed papers published the day of • Read Collections including: Reflections, acceptance Minireviews and Thematic Series *ASBMB has eliminated color figure fees for Regular ASBMB www.asbmb.org/publications members publishing as corresponding authors.