CONTENTS

NEWS FEATURES PERSPECTIVES

2 18 31 PRESIDENT’S MESSAGE SOLVING THE FACULTY EDUCATION Biochemists, unite! DIVERSITY PROBLEM Starting the organelle wars 3 24 34 NEWS FROM THE HILL MEET ANNE-CLAUDE GINGRAS DUE DILIGENCE Let’s talk about reproducibility Pixel perfect 28 4 MEET STEVE CARR 36 MEMBER UPDATE OUTREACH 6 18 Eective communication: dream or reality? RETROSPECTIVE 37 6 Susan Lindquist (1949 – 2016) ESSAY 9 ressa C. Stadtman (1920 – 2016) 37 Is a tool or a discipline? 38 Working at Manylabs, 12 an open science space NEWS 40 Just like Boyd 12 Cox wins Tabor award for work on extracellular matrix 13 Hidden information in mRNA 42 THE DO-OVER 14 If I could turn back time LIPID NEWS PI-PLC β1 in dierentiation 44 and disease 31 OPEN CHANNELS Bradley Graba Make or break 15 describes how he discovered a new JOURNAL NEWS way to teach cell 37 15 A factory runs riot biology to high- 16 Predicting when blood goes bad school students 17 Targeting for ALS treatment using Twitter. 6 42

THE DO-OVER

MARCH 2017 ASBMB TODAY 1 PRESIDENT’S MESSAGE

THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY Biochemists, unite! OFFICERS COUNCIL MEMBERS By Natalie Ahn Natalie Ahn Squire J. Booker President Victoria J. DeRose Wayne Fairbrother Steven McKnight Karen G. Fleming he American Society of Past President Rachel Green Biological Chemists, Jennifer DuBois Susan Marqusee Jared Rutter Secretary T which later became Celia A. Shier the American Society for Toni M. Antalis Michael Summers Treasurer Biochemistry and Molecu- ASBMB TODAY EDITORIAL lar Biology, was founded EX-OFFICIO MEMBERS ADVISORY BOARD more than 100 years ago. Natalie Ahn Rajini Rao Steven McKnight Chair e founders’ aim was to Co-chairs, 2017 Annual Charles Brenner embrace the biological Meeting Program Past Chair sciences from the chemical Committee Ana Maria Barral point of view and separate Cheryl Bailey Floyd “Ski” Chilton Chair, Education and Henrik Dohlman biochemistry from physiol- Professional Development Peter J. Kennelly ogy as a distinct scientic Committee Beronda Montgomery A. Maureen Rouhi pursuit. Our elds of Daniel Raben Chair, Meetings Committee Melissa Vaught biochemistry and molecular Binks W. Wattenberg Takita Felder Sumter biology dened the molecu- lar and chemical mecha- Chair, Minority Aairs ASBMB TODAY Committee Angela Hopp nisms that govern biological omas Baldwin Executive Editor, processes, fostering one of Chair, Public Outreach [email protected] Committee the most productive areas of Rajendrani Mukhopadhyay Wesley Sundquist Managing Editor, scientic investigation. Chair, Public Aairs [email protected] Today, the ASBMB Advisory Committee John Arnst continues to stand for the Amnon Kohen Science Writer, discovery and understanding Chair, Publications [email protected] Committee Valery Masterson the molecular mechanisms Designer, Lila M. Gierasch of life at deeper levels. We [email protected] tion for discovery across the wide Editor-in-chief, JBC Ciarán Finn stand for education: We provide each spectrum of biological and medical A. L. Burlingame Web Editor, new generation of and edu- sciences? Binks Wattenberg, Enrique Editor, MCP c[email protected] cators with mentorship and resources De La Cruz and Dan Raben begin a Allison Frick Edward A. Dennis to teach critical thinking, problem Editor-in-chief, JLR Media Specialist, discussion to answer this question for [email protected] William L. Smith solving and the other skills of great biochemists in their Perspectives essay Barbara Gordon Editor-in-chief, JLR scientists. We are prominent national Executive Director, on page 37. Keeping our community [email protected] advocates: We reach out on behalf of alive enables each of us to ourish. our members and the larger commu- You can help make us even stron- nity of scientists to inform govern- ger. Not a member of the ASBMB? For information on advertising, contact Pharmaceutical mental and nonscientic groups about Please join our community today. Media Inc. at 212-904-0374 or [email protected]. the consequences of policy decisions Already a member? Enlist a colleague on science. We also inform scientists to join too. It’s easy: Go to www. about policies that aect our research asbmb.org/membership/ or email and teaching. And, most importantly, [email protected]. www.asbmb.org/asbmbtoday we foster community by creating a PRINT ISSN 2372-0409 home for people to nd collabora- Articles published in ASBMB Today reect solely tions, share ideas and promote careers. Natalie Ahn the authors’ views and not the ocial positions of ([email protected]) of the the American Society for Biochemistry and Molecular What does it mean to be a bio- Biology or the institutions with which the authors University of Colorado, Boulder, is are aliated. Mentions of products or services are chemist or molecular biologist as our president of the ASBMB. not endorsements. elds increasingly become the founda-

2 ASBMB TODAY MARCH 2017 NEWS FROM THE HILL Let’s talk about reproducibility By Benjamin Corb

n 2015, Leonard Freedman, the fact is that we need more data before Societies for Experimental Biology, founder and president of the we can draw rm conclusions. set the issue of reproducibility as the I Global Biological Standards Initia- Researchers at the Center for Open need for scientists to be transparent, tive, and colleagues published a report Science recently began their own careful, diligent about recordkeeping, that claimed $28 billion worth of analysis on reproducibility, specically and mindful of reducing potential biomedical research is irreproducible. in cancer research projects (3). eir pitfalls, such as conrmation bias and e amount accounts for more than preliminary results are complicated. poor study design, while conduct- 50 percent of all preclinical Project researchers are examining 29 ing research. Scientists rightfully feel research grants. papers published in Science, Nature proud of the enormous contribu- is analysis, published in PLOS and Cell since 2012, repeating the tions made by biomedical research, Biology (1), shook scientists and same experiments and asking whether but they can get defensive about science advocates alike. Articles and or not they can reproduce the nd- their work, which can complicate the blog posts critical of the study have ings. One unique aspect of this repro- issue. Moreover, even the denition been published in the 18 months since ducibility eort is its transparency. of what constitutes reproducibility is Freedman’s analysis was published, Unlike previous eorts that have not murky, because science, particularly including by us and others, that were shared which papers they attempted biological science, is complex. Small critical of his study, citing concerns to reproduce, this group is publish- environmental dierences from one over Freedman’s potential conicts of ing their ndings from beginning to lab to another or unclear methodology interest (2). end — the papers they reviewed, the explanations can aect the ability of e inability of scientists to procedures and methods they fol- one researcher to reproduce the reproduce other scientists’ ndings is lowed, and their entire results are all results of another. an issue that the biomedical research available for review and scrutiny. Sean Nevertheless, rather than overreact- enterprise should be concerned about, Morrison, a senior editor of eLife, told ing to criticisms regarding reproduc- especially given that so much of the Nature, “For people keeping score ibility, let’s commit to the goal of research is funded by the federal at home, right now it’s kind of two government, which is to say taxpay- out of three that appear to have been making our scientic work careful, ers. Being good stewards of taxpayer reproduced” (4). scholarly and impactful. If we articu- money must mean conducting sound Conversations about reproducibil- late this goal clearly, then the enter- science. Sound science requires ity can be dierent among scientists prise will be better protected against reproducibility. But is the amount of because the importance of the issue any future criticisms, and perhaps research irreproducibility in the life may vary signicantly across dier- then we’ll show the criticisms to be sciences really so clear-cut that we can ent disciplines. Some eorts, like one irreproducible. chastise an entire community? e led by the Federation of American

Benjamin Corb REFERENCES ([email protected]) is director 1. Freedman, L. P., et al. PLOS Biol. 13, e1002165 (2015). of public affairs at the American 2. http://policy.asbmb.org/2015/06/22/research-reproducibility-rises-to-the-top/. Society for Biochemistry and 3. Nosek, B. & Errington, T. eLife 6, e23383 (2017). Molecular Biology. Follow him on Twitter at twitter.com/bwcorb. 4. Baker, M. & Dolgin, E. Nature 541, 269 (2017).

Interested in science policy? Follow our blog for news, analysis and commentary on policy issues aecting scientists, research funding and society. Visit policy.asbmb.org.

MARCH 2017 ASBMB TODAY 3 MEMBER UPDATE

Six ASBMB members named fellows of the National Academy of Inventors Francis Barany of Weill Cornell University, Barbara D. Boyan of Virginia Commonwealth University, Paul L. Modrich of Duke University, Nicholas Muzyczka of the University of Florida, Ronald T. Raines of the University of Wisconsin–Madison and Bruce W. Stillman of Cold Spring Harbor Laboratory have been nominated as 2016 fellows of the National Academy of Inventors. NAI fellows are named inventors on U.S. patents who are nominated by their peers for their outstanding contribu- tions as innovators. Fellows are recognized for having a signicant eect on society through innovations in patents and licensing as well as discovery and technology. ese six members, along with the other 2016 NAI fellows, will be inducted as part of the Sixth Annual Confer- ence of the National Academy of Inventors in April.

BARANY BOYAN MODRICH MUZYCZKA RAINES STILLMAN

Serio to be dean Hartl and Schulman named program pairs renowned scientists with leading biomedical research at UMass Amherst visiting professors institutions as a means of promoting Tricia R. Serio, F. Ulrich Hartl, intellectual exchange, collaboration professor and head director of the and discovery. of the department department of of molecular and cellular biochem- In memoriam: cellular biology istry at the Max P. Michael Conn SERIO at the University HARTL Planck Institute of of Arizona, will Biochemistry, and P. Michael Conn, senior vice become the dean of the College of Brenda Schul- president for research, associate pro- Natural Sciences at the University of man, the Joseph vost, and the Robert C. Kimbrough Massachusetts Amherst in August. Simone vhair in professor of internal medicine with a Serio takes over the department basic research at joint appointment in the department from Steven Goodwin, who is step- St. Jude Children’s of and biochemistry at ping down after leading the college SCHULMAN Research Hospital, Texas Tech University Health Sciences and one of its predecessors, the have been named Center, died in November. College of Natural Resources and the as 2017 Vallee visiting professors. Conn identied an underlying Environment, since 2002. Hartl’s research explores protein biological principle that has sig- Serio’s research is focused in the folding and quality control. Recently, nicantly altered the understanding eld of protein folding, where she he has focused on understanding the of cellular mutations that result in seeks to comprehend the mechanisms molecular mechanisms underlying human disease. His work has shown by which protein conformations can neurodegenerative disorders. the potential for the development of act as elements of inheritance and Schulman’s research focuses on the new therapeutic treatments. infectivity. structural basis for post-translational A highly accomplished researcher, Serio brings leadership and a modication by ubiquitin and ubiqui- Conn won, among numerous awards distinguished academic career to her tinlike proteins. and honors, the J. J. Abel Award of new role. e Vallee Visiting Professorship the American Society for Pharmacol-

4 ASBMB TODAY MARCH 2017 ogy and Experimental erapeutics Originally An important gure in the as well as the Miguel Aleman Prize, born Evgeny neuroscience community, Roberts Mexico’s national science medal. Rabinowitch in discovered the presence of abnormally Conn authored and co-authored Krasnodar, Russia, large quantities of γ-aminobutyric more than 350 publications and wrote Roberts moved to acid in the brain in 1949. In 1954, he and edited more than 200 books. Detroit in 1922. went on to work at the City of Hope He served as president of the Endo- ROBERTS He obtained his Medical Center in Duarte, California, crine Society, during which time he B.S. from Wayne where he later created an interdisci- founded the forerunner to the Hor- University in 1940 and received his plinary division of neurosciences, the mone Health Network, a group that M.S. and Ph.D. at the University of rst of its kind. serves as a public education resource Michigan in 1941 and He is survived by his wife, Ruth on hormone-related issues. 1943, respectively. Roberts; his son, Paul; his daughters, Shortly after his graduate work, Judith and Miriam; and his ve In memoriam: Roberts was employed to work on grandchildren. the Manhattan Project, serving as an Eugene Roberts assistant head of the project’s inhala- Eugene Roberts, distinguished tion research program. After the war, Erik Chaulk ([email protected]) Roberts joined Washington University is a peer-review coordinator and emeritus at the City of Hope digital publications web specialist Medical Center, died of pneumonia in in St. Louis, Missouri, in the division at the ASBMB. November. He was 96. of cancer research.

Upcoming ASBMB events and deadlines

April 5 – 6: ASBMB Hill Day

APR April 22 – 26: ASBMB annual meeting, Chicago

May 2: ASBMB Special Symposium: Evolution and Core Processes in Expression oral abstract deadline

MAY May 5: IMAGE Grant Writing Workshop application deadline May 9: ASBMB Special Symposium: Evolution and Core Processes in Gene Expression early registration deadline May 9: ASBMB Special Symposium: Transforming Undergraduate Education in the Molecular Life Sciences early registration deadline May 15: e Marion B. Sewer Distinguished Scholarship for Undergraduates application deadline May 24: ASBMB Special Symposium: Evolution and Core Processes in Gene Expression poster submission deadline May 31: ASBMB Special Symposium: Transforming Undergraduate Education in the Molecular Life Sciences poster submission deadline

June 8: ASBMB Special Symposium: Evolution and Core Processes in Gene Expression registration deadline June 15: ASBMB Special Symposium: Transforming Undergraduate Education in the Molecular Life Sciences JUNE registration deadline June 22: ASBMB Special Symposium: Membrane-Anchored Serine Proteases oral abstract deadline June 22 – 24: IMAGE Grant Writing Workshop June 29: ASBMB Special Symposium: Membrane-Anchored Serine Proteases early registration deadline

MARCH 2017 ASBMB TODAY 5 RETROSPECTIVE Susan Lindquist (1949 – 2016) By Jeery W. Kelly & Richard I. Morimoto

usan Lindquist was University of Chicago. It one of those very was a chance meeting with S rare, incredibly Sue when she had joined special individuals who Hewson Swift’s laboratory inspired many scientists, as a postdoctoral fellow whether through her semi- and was writing her Ph.D. nars, an insightful question (she had done her at a research talk or poster graduate work with Matt session, or her prolic and Meselson of Harvard Uni- innovative contributions versity) that led me to the to the scientic literature. wonders of the heat shock Sue also wrote frequently response and the lifelong about our roles and pleasure of knowing Sue. responsibilities as academic Her infectious enthusiasm scientists and the impor- was unmatched, and this tance of being supportive led me, upon completion and reliable mentors. She of my doctoral work at was an outspoken advocate Chicago, to join Mesel- for women and minority son’s lab as a postdoctoral scientists. Her passion, fellow. Upon returning to out-of-the-box thinking, Chicago and joining the and enthusiasm for science faculty of the biochemistry were contagious. Sue’s life and molecular biology was cut short by cancer on department at North- Oct. 27. For those who western University, our knew her, it will come as laboratories re-engaged, no surprise that she fought exchanged students and this horrible disease to the reagents, and had numer- very end through a combi- ous joint meetings. It nation of grit and scholar- PHOTO COURTESTY OF CEAL CAPISTRANO/WHITEHEAD INSTITUTE was a wonderful time. A ship, which is how she Susan Lindquist few years later, together lived her honorable life. lenges we encountered in FoldRx was with Betty Craig at the I, Je Kelly, rst came to know not having enough money to pursue University of Wisconsin–Madison, we of Sue Lindquist through her amaz- Sue’s dream of using yeast-based expanded our mega-group meetings to ing contributions to the scientic neurodegenerative disease models to form the Midwest Stress Response and literature. I recall meeting her for discover small-molecule drugs — a Chaperone Meeting, which continues the rst time at the University of dream that nally is being realized in its 22nd year with the same spirit Chicago. She was charming, insight- in another company, Yumanity (see of support of young investigators and ful, incredibly intelligent and, in below). rough sacricing her own great science. many respects, larger than life! After a scientic agenda, Sue enabled FoldRx Sue started her academic career decade of friendship, we co-founded to commercialize Tafamidis, a drug as a professor in the department of FoldRx Pharmaceuticals. rough the now sold by Pzer, to ameliorate the molecular biology at the University of challenges typical of successful biotech transthyretin amyloidoses. Chicago, and then she moved to the ventures, Sue remained a wonder- I, Rick Morimoto, interacted with Massachusetts Institute of Technol- ful friend and colleague until her Sue Lindquist as far back as when I ogy as a professor of biology until her untimely death. One of these chal- was a rst-year graduate student at the death. Lindquist served as director of

6 ASBMB TODAY MARCH 2017 PHOTO COURTESTY OF EDWARD BUCKBEE Lindquist with her husband, Edward Buckbee, and her daughers, Alana (left) and Nora (right), when she received the Naitonal Medal of Science in 2010. the Whitehead Institute from 2001 Medicine, the American Philosophi- cell-signaling pathways from being to 2004, becoming one of the rst cal Society, the American Academy compromised by mutations in other women in the nation to lead a major of Arts and Sciences, and the British proteins. If Hsp90 function was low- independent biomedical research Royal Society. ered — by environmental stress, for organization. She was also among the Sue is perhaps best known for her example — mutated proteins would rst women to serve on the board prion research. She provided strong fold dierently and new traits would of directors of a major pharmaceuti- evidence for a new paradigm in genet- appear. She also pioneered how stress- cal company, Johnson & Johnson. ics — that inheritance could result responsive signaling pathways like Besides being a Whitehead Institute from self-perpetuating protein aggre- the heat shock response regulated this member, Sue was an associate member gate structures. She discovered genetic capacity. Sue was considered one of of the Broad Institute of MIT and modiers of this protein-only form of the experts on cellular protein folding, Harvard, an associate member of the inheritance, such as the disaggregase and she studied how chaperones like David H. Koch Institute for Integra- Hsp104. ese insights led to discov- Hsp90 could inuence func- tive Cancer Research at MIT, and a eries that contributed signicantly tion as it relates to cancer and other longtime investigator of the How- to understanding devastating neuro- diseases. ard Hughes Medical Institute. She logical maladies such as Alzheimer’s, Many of Sue’s most insightful dis- received numerous awards over the Parkinson’s and Huntington’s diseases. coveries were enabled by her devotion course of her career, including the She was also very well known for the to her favorite organism, Saccharo- National Medal of Science, the high- concept that molecular chaperones, myces cerevisiae, and her fearless- est scientic honor bestowed by the such as Hsp90, functioned as capaci- ness to jump to mice, iPS-derived United States (awarded by President tors of morphological evolution by human cells or whatever organism Barack Obama). She was an elected regulating the inuence of other was most appropriate to demonstrate member of the National Academy of mutated proteins. For example, Sue the relevance of her ndings in yeast. Sciences, the National Academy of showed that Hsp90 could protect CONTINUED ON PAGE 8

MARCH 2017 ASBMB TODAY 7 CONTINUED FROM PAGE 7

is approach is exemplied by Sue’s discovery that three copies of the α-synuclein gene compromised vesicular tracking, which now is accepted as the basis for some of the Parkinson’s disease — a discovery that was made in yeast. is concept of making discoveries in yeast that translate to neurodegenerative diseases underlies the strategy for at Yumanity erapeutics, a company Sue co-founded with Tony Coles in 2015. Ulrich Hartl, a Max Planck Inves- tigator and longtime friend of Sue Lindquist, captured the feelings of many by telling us, “We are not only losing an eminent leader of the eld but also a warm-hearted and generous colleague and an advocate for young scientists. She will live on in our memories and through her fundamen- tal contributions to science.” Sue loved the two-steps-forward- one-step-back process of scientic dis- covery as much as she loved dancing. She was an eternal optimist. By seeing through hazy data to make discover- ies like few others could, she trained numerous scientists, providing the inspiration that would convince some- one to pursue science for a lifetime. We close with a fond memory. PHOTO COURTESY OF EDWARD BUCKBEE Lindquist at the U.K.’s Royal Society in 2015 when she became a member. Sue, like many gifted people, was a bit absentminded when it came to they were already en route. At this discreet, all the participants watched practical things. One memorable event point, with a fair amount of commo- in amazement as Sue retrieved her unfolded at the 2006 Protein Folding tion, it was discovered that Patricia computer. is contributed further to in the Cell meeting in Saxtons River, Clark of Notre Dame University had her larger-than-life persona. Vermont. One of us, Morimoto, grown up nearby in New Hampshire Rest in peace, dear friend — you had picked up Sue at her home in and that her dad ew a helicopter and are sadly missed. Boston, and together with Betty Craig had one in his yard. In quick course, and Carol Gross of the University of it was arranged for the computer to Jeffery W. Kelly (jwk@scripps. California, San Francisco, enjoyed the be delivered to Hanscom Field near edu) is the Lita Annenberg Hazen two-and-a-half-hour drive to Ver- Boston and brought to the meeting by Professor of Chemistry in the mont accompanied by laughter and Patricia’s dad. e next morning, just department of chemistry and the chairman of the depart- discussions among longtime friends. when the meeting participants were ment of molecular medicine at Arriving at Saxtons River, we discov- gathered outside for a coee break, the Scripps Research Institute. ered that Sue had left her computer at we heard the characteristic sound of Richard I. Morimoto (r-morimoto@ home. inking that we would catch a helicopter as it got closer and closer northwestern.edu) is the Bill and Gayle Cook Professor of Biology some of the Boston colleagues coming and nally landed in the adjacent open in the department of molecular biosciences at up to Saxtons River, we quickly made eld. Even though Sue had hoped Northwestern University and the director of the a number of calls, but to no avail, as that this step in the process would be Rice Institute for Biomedical Research.

8 ASBMB TODAY MARCH 2017 RETROSPECTIVE Thressa C. Stadtman (1920 – 2016) By P. Boon Chock & Rodney L. Levine

hressa “Terry” C. Stadt- of Cellular Physiology and man died peacefully at Metabolism at the NIH in the T her home on December newly formed National Heart 11 at age 96. She is remem- Institute, he invited Terry to bered as a pioneer in anaerobic move with him to continue electron transport, vitamin her work on bacterial choles- B12 metabolism and selenium terol oxidase. At that time, biochemistry. the NIH was one of the few Stadtman and her hus- institutions that would hire a band, Earl, created a superb married couple as independent mentoring environment at the investigators. Earl was able to National Institutes of Health tag along as the accompanying in which many outstanding spouse because Annsen also scientists were trained. e oered him a position. ey Stadtmans’ rigor in scientic moved to the NIH in 1950. inquiry and their superbly suc- Terry retired from the NIH cessful mentoring is aection- in 2009, 59 years after her ately known as “the Stadtman arrival. Way” (see https://history.nih. e Nobel laureate Michael gov/exhibits/stadtman). eir Brown at the University of Journal Club, initially feared Texas Southwestern Medi- cal Center, who did a post- by newly arrived trainees PHOTO COURTESTY OF BUHM SOON PARK doctoral stint at NIH, says, and then enthusiastically Thressa C. Stadtman “What I remember most about embraced, was the furnace B12. For her thesis work, she inves- Terry was her enthusiasm for where scientic rigor was forged. tigated the mechanism of methane science … Terry was outgoing and No detail or question was too trivial fermentation by the activities of two always eager to discuss data, whether to be brushed aside. e Stadtman anaerobic microorganisms, Clostrid- they were her own or that of others. Way also included generous sharing ium sticklandii and Methanococcus Her interest in biology was as pure of credit in publications with more vannielii, which she isolated from the as that of anyone I ever knew. Terry junior scientists. Camaraderie, lively mud that she scooped up from the loved scientic beauty without any and friendly discussions, and lab par- San Francisco Bay. While working in concern for its utility. She was a scien- ties led to lifelong friendships among Barker’s lab, she met his technician tist’s scientist.” those lucky enough to be shown the and graduate student Earl Stadtman. Terry’s initial scientic goal at the Stadtman Way. ey were married in 1943. NIH was to elucidate principles of Terry was born in 1920 in Sterling, After graduation in 1949, Terry and biochemistry by studying the metabo- New York, and studied bacteriology at Earl moved to Boston, where she did lism of anaerobic bacteria, organisms Cornell University, where she received postdoctoral training with Christian that seem capable of almost any imag- her B.S. in 1940 and her M.S. in Annsen at Harvard Medical School inable chemical reaction. While chem- 1942. She earned her Ph.D. from the while Earl worked with Fritz Lipmann ists had to use harsh solvents and high University of California, Berkeley, at the Massachusetts General Hos- temperatures to make many reactions under the guidance of Horace Barker, pital. When Annsen was oered a who discovered the active form of position as the chief of the Laboratory CONTINUED ON PAGE 10

MARCH 2017 ASBMB TODAY 9 CONTINUED FROM PAGE 9

happen, these microbes easily achieved the same reactions with extraor- dinarily high yields at ambient temperatures in aqueous solutions! Using extracts from M. vannielii and C. stick- landii, Terry studied the mechanisms of amino acid fermentation and methane production from carbon dioxide. Her investigations gave insights into anaerobic electron transport and vitamin B12 metabo- lism. In the course of these studies, Terry and her colleagues discov- ered four of the vitamin B12-dependent enzyme systems. She also estab- lished that the free form of B12 can function as a methyl-group carrier and that its deoxyad-

enosyl coenzyme forms PHOTO PROVIDED BY P. BOON CHOCK & RODNEY LEVINE serve as hydrogen Stadtman with her husband, Earl, at their Ph.D. graduation carriers. Her ndings doxin reductase in human lung adeno- established that seleno-phosphate is provided the basis of our understand- ing of methane biosynthesis. carcinoma contained selenocysteine. the immediate selenium donor for the Terry’s pioneering work on Her studies then established that the biosynthesis of selenium-containing selenium biochemistry began with codon for selenocysteine in thiore- biomacromolecules, selenocysteine in her 1972 discovery that protein A, doxin reductase was UGA, which proteins and 5-methylaminomethyl- a low-molecular-weight subunit of was normally the terminator codon. 2-selenouridine in seleno-tRNAs. the Clostridial glycine reductase, is a By collaborating with August Böck A series of publications from 1996 selenium-containing protein. In 1976, of Munich, Dolph Hateld of the until her retirement elucidated the Terry and her colleagues became the National Cancer Institute and others, mechanism by which selenophosphate rst to demonstrate that the selenium she soon was established that seleno- synthetase catalyzes the synthesis of was present as selenocysteine. ey cysteine is inserted co-translationally selenophosphate. It’s not surpris- showed that selenocysteine plays an rather than as a post-translational ing that Terry became known as the essential role in the catalytic activity of modication. Hence, selenocysteine “mother of selenium biochemistry.” many selenoenzymes. Terry went on to came to be known as the 21st amino Terry was elected to the National establish that selenium is an essential acid, sharing its codon with the termi- Academy of Sciences in 1981 and constituent of several other enzymes. nation process. the American Academy of Arts and In addition to its incorporation as a In 1984, Terry and colleagues Sciences in 1982. Among her awards, selenocysteine residue, the selenium showed that the selenium-containing Terry received the William C. Rose can be coordinated with molybdenum nucleoside in several bacterial seleno- Award of the ASBMB in 1986, the in a molybdopterin cofactor. She tRNAs was 5-[(methylamino)methyl]- Klaus Schwarz Medal from the Inter- extended her ndings to eukaryotes 2-selenouridine. Collaborating with national Association of Bioinorganic with her demonstration that a thiore- Robert Balaban at the NIH, she Scientists in 1988, and the inaugural

10 ASBMB TODAY MARCH 2017 L’Oreal Lifetime Achievement Award for Women in Science from L’Oreal–UNESCO in 2000. e organism Methano- spaera stadtmaniae is named in her honor. e American Society for Biochemistry and Molecular Biology gives out the Earl and ressa Stadtman Distinguished Scientist Award every other year to an estab- lished scientist for his or her outstanding achievement in basic research. e award alter- nates with the Earl and ressa Stadtman Young Scholar Award, which goes to a sci- entist with 10 years or less of experience as an independent investigator. e awards were established by friends and colleagues of the Stadtmans to preserve their legacies as scientists and mentors. Terry, with the whole- hearted support of Earl, championed and supported women in science. Terry was able to attend Cornell only because of scholarship support and working as a waitress for four hours a day. is is why Terry generously endowed the Stadtman Scholarship Fund for undergraduates and the PHOTO PROVIDED BY RODNEY LEVINE Stadtman Fellowship Fund for Stadtman tried her hand at viticulture. graduate students at Cornell. deeded their property to expand the “If we make a pinot noir wine with e funds provide support for women park. In accepting the gift, the park Burgundy grapes but with Napa Valley who are majoring in the sciences. commissioners gave that section of yeast and fermentation techniques, Being optimistic about the future for the park the legal name the Stadtman will it taste like a French Burgundy or women in science, she specied that Preserve. It features a mature forest, a California Pinot Noir?” eir answer when women no longer face road- steep slopes, oodplain, wetlands, a to the question turned out to be, blocks to careers in science, Cornell stream, and nearly a thousand azaleas “We’re not sure, but it’s a really good may redirect the Stadtman funds to and rhododendrons planted by Earl. wine!” support other groups who still face Terry also tried her hand at applied impediments in becoming scientists. biochemistry. In the early 1990s, she P. Boon Chock ([email protected]) Earl and Terry lived in a home purchased a rst-growth vineyard in and Rodney L. Levine on six acres adjacent to Rock Creek the Burgundy region of France known ([email protected]) are members Park in Washington, D.C., one of the by the name “Les Chouacheux.” of the laboratory of biochemistry of the National Heart, Lung and places President Abraham Lincoln She, Earl and a microbiologist friend Blood Institute, where Terry Stadt- sometimes took carriage rides to try from Berkeley, Terry Leighton, then man’s laboratory was located dur- to unwind a little during the Civil launched a classic Stadtman experi- ing her 59 years at the National War. After Earl’s death in 2008, Terry ment aimed at answering the question, Institutes of Health.

MARCH 2017 ASBMB TODAY 11 NEWS Cox wins Tabor award for work on extracellular matrix By Mariana Figuera–Losada

homas Cox at the Garvan Institute of Medical Research in T Australia won a Journal of Bio- logical Chemistry/Herb Tabor Young Investigator Award at the 2016 Matrix Biology Society of Australia and New Zealand Conference. Amanda Fosang of the Murdoch Childrens Research Institute in Australia, who is a JBC associate editor, presented the award to Cox. Cox obtained his Ph.D. in 2008 at the University of Durham in the U.K. He continued his training as a cancer-cell biologist at the Institute of Cancer Research in London and then PHOTO COURTESY OF THOMAS COX in the laboratory of Janine Erler at the Thomas Cox University of Copenhagen. He started cations that alter its biochemical and dous honor for me,” says Cox. “Over his own group at the Garvan Institute biomechanical properties and that the years, I have seen many fantastic of Medical Research in late 2016. lysyl oxidase and lysyl oxidaselike fam- junior researchers awarded this presti- He now is the matrix and metastasis ily members play an important role in gious prize and feel very privileged to group leader. this process. As a long-term goal, Cox be one of the 2016 recipients.” e Tabor award recognized Cox’s intents to establish a novel therapeu- research on the eects of extracellular tic approach to treat solid cancers by matrix remodeling on cancer progres- targeting ECM dynamics. Mariana Figuera-Losada ([email protected]) is an sion, metastasis and therapy response. “Being awarded the Journal of associate scientist at Albert He has shown that ECM remodeling Biological Chemistry/Herbert Tabor Einstein College of Medicine. is induced by post-translational modi- Young Investigator Award is a tremen-

The Marion B. Sewer Distinguished Scholarship for Undergraduates

Benefits: : $2,000 toward tuition for one academic year. Scholarship recipients are eligible to apply for an additional scholarship in subsequent years. Requirements: Must be a U.S. citizen, U.S. national or permanent resident. Students with DACA status also are eligible. Must be a full-time student at an accredited two- or four-year institution located in the U.S. or U.S. territories. Must have completed a minimum of 60 credit hours or equivalent, have a GPA of 3.0 or higher, and have faced significant educational, social, cultural or economic barriers in pursuit of education. Must also be committed to diversity on campus and in the scientific community as a whole and be an ASBMB member (membership can be processed at time of application). Application deadline: May 15, 2017 Learn more at www.asbmb.org/MinorityAffairs/UndergraduateScholarship/

12 ASBMB TODAY MARCH 2017 NEWS Hidden information in mRNA By Dawn Hayward

ust before the transla- beginning of messenger tion step of protein RNA can get “decapped” J synthesis, the cell by DCP2, the putative protects its messenger RNA enzyme in a large complex. with a 5′ methylguanosine By using a radioactivity triphosphate cap and a 3′ where the release of polyadenosine tail. Other methylguanosine diphos- modications can occur phate was detected if DCP2 within the message itself. succeeded in decapping the 6 One of these, called m Am, mRNA, researchers found appears on adenosine that transcripts beginning 6 nucleotides at the start of with the m Am modication transcripts and has a methyl were not as easily decapped group on both its sugar IMAGE PROVIDED BY SAMIE JAFFREY and destabilized. and nitrogenous base. is Modifications of the extended mRNA cap. Finally, the Jarey group modication was discovered 6 explored the phenomenon pression decreased m Am levels speci- in the 1970s but received little atten- cally, and its knockdown increased the of microRNA-mediated degradation tion, and its role was unknown. 6 of mRNA transcripts. is degrada- ratio between m Am and Am. In a paper published Dec. 21 in the Next the Jarey group looked at tion is important, as some transcripts journal Nature, Samie Jarey of the this modication’s role. While the cap are mysteriously resistant to its eects. Weill Cornell Medical College and and tail are known both to protect e group again looked at previ- 6 colleagues explored m Am in depth. and aid in translation initiation, mod- ously compiled translation eciency ey determined which enzyme spe- ications to the nucleotides them- data, this time in DICER knock- cically removes this modication and selves have been studied less. Jarey down cells, a key component of the the profound eects this mark has on calls these marks “hidden information degradation machinery. Transcripts 6 mRNA stability. sitting inside RNA molecules” and beginning with m Am did not change 6 Jarey says that the m Am modica- sought to uncover their signicance. signicantly, while others increased, tion largely was overlooked after its To gure out what m6A is doing, an indication of lowered susceptibility. 6 m initial discovery. e m Am modica- the group analyzed previously com- Jarey marvels at how the stability tion was present at less than 10 per- piled translation eciency data. is of these mRNAs was encoded: “It was 6 cent of the level of the m A modica- data reveal how well a large group actually in the nucleotides, some- tion, which also is found in mRNA. of mRNA transcripts is translated at thing that was invisible to standard e adenosine is modied only at its a given point, explains Jarey. e methods,” he notes. Next steps from nitrogenous base and occurs internally investigators sorted transcripts based this work include studying how levels rather than at the beginning of the on the rst nucleotide identity, A , of this modication are aected in transcript. In addition, FTO, the fat m disease states as well as identifying Cm, Gm or Um, and used specialized mass and obesity-associated protein, mapping techniques to identify those the methyl-transferase that adds this was identied as the “eraser” of the beginning with m6A . From this mark. 6 6 m 6 6 m Am mark. e m Am modication For the time being, m Am is back in analysis, m Am transcripts showed fell by the wayside. longer half-life and higher expression the spotlight. But by using analytical chemistry levels, an indication of stability. techniques, the Jarey group discov- Next, the group collaborated with Dawn Hayward ered that FTO actually prefers the Mergerditch Kiledjian of Rutgers 6 6 ([email protected]) is a gradu- m Am modication over m A. FTO University to study the decapping ate student at the Johns Hopkins showed a higher catalytic eciency of mRNA transcripts. e 5′ meth- University School of Medicine. 6 toward m Am. In cells, FTO overex- ylguanosine triphosphate cap at the

MARCH 2017 ASBMB TODAY 13 LIPID NEWS PI-PLC β1 in differentiation and disease By Lucio Cocco

vidence from several laboratories has highlighted the presence of E autonomous nuclear inositol lipid metabolism. e evidence sug- gests that lipid molecules are impor- tant components of signaling path- ways operating within the nucleus. e ndings are important, given the fact that nuclear signaling activity con- trols cell growth and dierentiation. Among the nuclear enzymes involved in this system, inositide-spe- cic phospholipase C, or PI-PLC, β1 is one of the most extensively studied enzymes. Besides the studies on its signaling activity, clinically oriented IMAGE PROVIDED BY LUCIO COCCO studies have shown that a mono-allelic Inositide-specific phospholipase C plays a role in MDS and a form of muscular dystrophy. deletion of the PI-PLCβ1 gene is asso- genic dierentiation. cells. Treatment with insulin induces ciated with the evolution of myelodys- Indeed, nuclear PI-PLCβ1 plays a dramatic decrease in the amount of plastic syndromes, or MDS, into acute a crucial role in the initiation of PI-PLCβ1. During dierentiation, myeloid leukemia. Studies also have the genetic program responsible for cyclin D3 and myogenin are elevated showed that increased PI-PLCβ1 gene muscle dierentiation: the enzyme in normal myotubes. When DM1 and expression, due to reduced methyla- activates the cyclin D3 promoter DM2 cells are induced to dierenti- tion and reactivation of its promoter, during the dierentiation of myo- ate, they do not show any increase in associates with responsiveness to blasts to myotubes. is indicates that these proteins. Forced expression of demethylating agents, such as azaciti- PI-PLCβ1 is essential for cyclin D3 PI-PLCβ1 in DM1 and DM2 cells dine, in MDS. Extensive clinical and promoter activation and gene tran- increases the expression of dierentia- molecular evaluation have aimed to scription through c-jun/AP1. tion markers myogenin and cyclin D3 establish a predictive role of increased Myotonic dystrophy is the most and enhances fusion of DM myo- β PI-PLC 1 gene expression during the prevalent form of muscular dystrophy blasts. ese results highlight again rst three cycles of treatment with in adults. DM type 1 and type 2 are that nuclear PI-PLCβ1 expression is a the demethylating drug azacitidine. dominantly inherited multisystem dis- key player in myoblast dierentiation, β e data obtained hint at PI-PLC 1 orders. DM1 is triggered by the path- functioning as a positive regulator in expression as a useful tool for the ological expansion of a CTG triplet the correction of delayed dierentia- early identication of a subgroup of repeat in the gene coding for DMPK, tion of human skeletal muscle. patients with a higher probability of the dystrophia myotonica-protein response to azacitidine. ese data kinase. A CCTG tetranucleotide suggest also a possible involvement of repeat expansion in the ZNF9 gene, nuclear PI-PLCβ1 in the early stages which encodes a CCHC-type zinc- Lucio Cocco ([email protected]) is a of hemopoiesis and specically in the nger protein, causes DM2. Unlike in professor and head of the cellular control of cell-cycle progression in normal myotubes, the level of expres- signaling laboratory in the depart- progenitor hemopoietic cells. Nuclear sion of PI-PLCβ1 in DM1 and DM2 ment of biomedical sciences at PI-PLCβ1 also is involved in myo- cells already is elevated in proliferating the University of Bologna in Italy.

14 ASBMB TODAY MARCH 2017 JOURNAL NEWS A factory runs riot By Catherine Goodman

Bacteria are at war. eir foes? Other microorganisms. eir weapons? Among other things, they deploy small chemicals called natural products. ese chemicals often are co-opted by humans for drugs, mak- ing it important to keep identifying natural products and the pathways by which they’re made. While these bio- synthetic pathways often have minor departures from rules developed over many examples, a recent paper in the Locations where the bacterial strains were collected. Journal of Biological Chemistry colleagues reported 14 thalassospi- of the thalassospiramide assembly line, reports an extreme case of rule-break- ramides from four types of ocean- only four of which were operational. ing that explains how a structurally dwelling bacteria. ey also wanted By pairing compound structures with diverse group of natural products, to determine the blueprint for the assembly lines, the authors could see called thalassospiramides, is made. assembly line because, as Qian recalls, how the four functional lines were Two of the common pathways that “We wondered how and why bacteria hiring, ring and reusing enzymes bacteria use to make natural products from dierent genera produce similar even more than anticipated based on rely on a series of enzymes linked compounds.” the previous report. Moreover, they together in long chains. e chained Surprisingly, the assembly line was discovered that attempts to outsource enzymes function much like factory sending some workers home for the an intact assembly line to a dierent workers at an assembly line: When a day, asking other workers to perform bacterial factory might have caused molecule arrives at their station, they their jobs two or three times, and the seemingly functional but unpro- add a new piece or adjust an existing bringing in workers from elsewhere ductive lines, as some of the individual piece and send it along. In this way, in the factory. As rst author and parts needed for the assembly line many copies of the same thing are then-postdoctoral fellow Avena Ross workers weren’t available in the new made eciently. recalls, “ e huge diversity of mol- factory. However, the bacterial foe doesn’t ecules seemed to be coming from a While some of these individual just sit around, waiting to be killed; single, quite simple assembly line that mechanisms of hiring, ring and the bacteria evolve to resist specic behaved in a highly unusual manner.” reusing enzymes to create compound natural products. So many assembly Since their rst study only exam- diversity have been seen in other natu- lines either swap workers with other ined four bacteria, teams led by ral product assembly lines, the new pathways or get the workers to make Qian, Moore and Ross — now a mechanisms as well as their combina- tweaks to create multiple, slightly faculty member at Queen’s Uni- tion are surprising. Moore notes that dierent molecules based on the same versity — suspected there might the assembly line “is able to break so overall blueprint. be more to learn. So they looked many of the conventional ‘rules.’” Ross believes more surprises await A team led by Pei-Yuan Qian at through the Marine Culture Col- as they determine how the rule-break- Hong Kong University of Science and lection of China, including samples ing occurs at the level of individual Technology and Bradley Moore at the from the Baltic and Bering seas, enzymes and reactions. Perhaps, in University of California, San Diego the coasts of Madagascar and New times of war, rules are meant to be previously had teamed up to study the Zealand, and everywhere in between, broken. assembly line that makes thalassospi- to assemble 130 dierent strains of ramides. ese compounds inhibit an bacteria, leading to 21 new enzyme called calpain protease, which thalassospiramides. Catherine Goodman ([email protected]) is the is important in neurological disorders, By looking at the DNA sequences JBC’s scientific editor. Follow cancer and other medical conditions. for a subset of the bacteria they col- her on Twitter at twitter.com/ In earlier work, Qian, Moore and lected, the authors found seven copies cate_goodman.

MARCH 2017 ASBMB TODAY 15 JOURNAL NEWS

Predicting when blood goes bad By John Arnst

Despite the best eorts of chance of heritability for the blood banks and networks, some entire set of metabolites related to blood bags end up spoiling before the pathways. “We observe that they can make it to patients in you don’t just sort of randomly need. A blood bag’s spoilage inherit high levels of 2, 3-diphos- depends on the red blood cells’ phoglycerate or pyruvate, but ability to avoid hemolysis caused rather that the entire block of by low ATP levels. e break- metabolites from the intermedi- ing of red blood cells can release ate part of the pathway are all byproducts, such as iron and inherited at a higher or lower hemoglobin, that become toxic in level,” says omas J. Raife, a a free-oating form by inten- co-author at the UW’s depart- sifying bacterial infections and ment of pathology and laboratory interfering with the nitric oxide medicine. “ is means a pheno- signaling that is key for type.” vasodilation. e researchers proposed In a paper published in the phenotypes for both high and journal Molecular & Cellular low levels of ATP after six weeks Proteomics, researchers at the of storage. e phenotypes cor- University of Wisconsin–Madi- related to ve key parameters, son have generated a model for which include pH and concentra- predicting post-storage ATP levels tions of phosphofructokinase, an in blood based on the concentra- centrifuged the hemoglobin out of essential enzyme in glycolysis, as tions of ve key metabolic factors. whole red blood cells, as it makes up well as the proteins Band 3, BPGM ey found these factors exhibited about 98 percent of the cells’ protein and CA1. As a trio, the latter proteins high heritability and were inherited as content. e researchers digested the correlated negatively with post- a block rather than individually. remaining proteins with trypsin and storage ATP conditions, making lower “We can use this model to identify subjected them to a novel proteomics concentrations desirable for blood blood that can be potentially stored and metabolomics approach. e viability. for longer or shorter periods as well approach involved two sets of liquid is phenotypic existence of vary- as potentially identify other factors to chromatography with tandem mass ing levels of glycolysis also could have make all blood store longer,” says Erin spectrometry, separately optimized for implications for a variety of metabolic M. M. Weisenhorn. Weisenhorn, the acidic and basic metabolites, com- diseases, says Weisenhorn. One such rst author on the paper, is a graduate bined with a standard analysis by gas correlation is the Warburg eect, student in Joshua J. Coon’s group. chromatography and mass spectrom- in which a cancer is associated with To generate this model, the etry. ey quantied 328 separate extremely elevated levels of glycoly- researchers performed a comprehen- metabolites from the red blood cells, sis. “You can potentially imagine if sive metabolomics and proteomics including those from the glycolysis someone inherits higher levels of these study to examine heritability of and pentose phosphate pathway. glycolytic proteins or metabolites and metabolites associated with ATP e researchers then identied 119 has naturally higher ux through this consumption in the red blood cells in membrane proteins and 148 metabo- pathway, then they might be more 18 pairs of twins. Heritability is the lite concentrations that had a herita- predisposed towards cancer.” proportion of phenotypic variability bility rate of more than 30 percent, due to genetic factors. which previously had been established e researchers wanted to examine John Arnst ([email protected]) is as a benchmark level of heritability in ASBMB Today’s science writer. the proteins in the red blood cells’ studies with the same group of twins. Follow him on Twitter at twitter. membranes because of their high e researchers additionally found com/arnstjohn. abundance there. To do this, they that there was a 60 to 90 percent

16 ASBMB TODAY MARCH 2017 JOURNAL NEWS

Targeting cholesterol for ALS treatment By Monika Deshpande

In 2014, amyotrophic brospinal uid. e level of lateral sclerosis came into cholesterol, specically non- the limelight with the Ice esteried cholesterol, was Bucket Challenge. ALS, higher in the cerebrospinal also known as Lou Gehrig’s uid of the ALS patients. disease, is a debilitating and Griths and his team fatal disorder that attacks explained this observation the nerve cells. ere is no by pointing to the greater cure for ALS. In a recent number of neurons that die paper in the Journal of during ALS. e dying neu- Lipid Research, researchers rons release more choles- showed for the rst time terol from their membranes, that patients with ALS have and the metabolic pathways higher levels of cholesterol are unable to remove this in the uid surrounding the excess cholesterol. brain than people without Alternatively, the inves- the disease. e research- tigators proposed, choles- ers propose that a potential terol metabolism through therapeutic approach for IMAGE COURTESY OF FRANK GAILLARD/WIKIMEDIA a pathway called LXRβ ALS treatment could be to The brain of an ALS patient. signaling could be defective use drugs that reduce the in ALS patients. Support Some studies indicated that statins, levels of cholesterol in the brain. for this hypothesis comes from mice drugs that reduce cholesterol, exac- ALS typically starts with twitch- that are decient in the LXRβ gene. erbated ALS. However, a 2013 study ing of muscles and ultimately leads to ese mice, similar to ALS patients, denitively showed that the detrimen- paralysis and respiratory failure. About have neuronal inammation and high tal eects of statins were abolished 20,000 Americans have this disease cholesterol levels in the spinal cord. when adjusted for age of onset and at any given time. Riluzole, the only Furthermore, other metabolites of body mass index. “In the light of these drug for ALS approved by the U.S. cholesterol that are part of the LXRβ studies, and considering that about Food and Drug Administration, has 25 percent of the body’s cholesterol is signaling pathway also were reduced been on the market since 1995 and present in brain, it seemed like cho- in the cerebrospinal uid of ALS shows only modest slowing of progres- lesterol might be a potential target for patients. sion in a fraction of patients. ere ALS studies,” says Griths. “We think that people with ALS is no current treatment that stops or e investigators used serum, the are unable to dispose of the nonesteri- reverses ALS. clear liquid separated from clotted ed cholesterol from brain eciently, In the JLR study, led by William blood, from 35 ALS patients and 24 leading to the presentation of the J. Griths of the Swansea University healthy individuals, and cerebrospinal disease,” explains Griths. Griths is Medical School and Martin Turner of uid, the colorless uid surrounding optimistic that “not only will our work the University of Oxford in the U.K., the brain and spinal cord, from 20 provide a method to diagnose ALS but the researchers investigated whether ALS patients and 15 healthy indi- be useful to stratify people for more targeting cholesterol was an option viduals for the study. ey measured ecient clinical trials and could also for ALS treatment. Earlier studies cholesterol and its metabolites by mass provide a route to development of a indicated that an increase in choles- spectrometry. new drug to treat ALS.” terol caused oxidative stress that led eir analysis of the serum showed to neuronal death in ALS. Secondly, no signicant dierences in cholesterol a gene critical for cholesterol metabo- Monika Deshpande or most of its metabolites between ([email protected]) is a post- lism called CYP27A1 was identied as ALS patients and controls. However, doctoral fellow at Johns Hopkins a susceptibility gene that increased a Griths and colleagues observed the University. person’s likelihood of contracting ALS. most interesting results in the cere-

MARCH 2017 ASBMB TODAY 17 FEATURE Solving the faculty diversity problem A model shows it’s possible to diversify the workforce within a single tenure cycle. e solution has to do with hiring decisions By Angela Hopp

ast fall, a paper in the journal member from an underrepresented eLife called into question the wis- background every year for six years, L dom that the key to diversifying the system would reach parity with the faculty hiring pool is focusing on the Ph.D. pool in one tenure cycle,” building the talent pool of underrep- explains Gibbs. resented scientists. e paper showed Bottom line: Diversifying the fac- that diversity within the Ph.D. pool ulty is not unsolvable. As Gibbs puts has increased dramatically. e prob- it, “the mathematical reality is that it lem is that scientists from underrepre- takes around 100 assistant professor sented backgrounds aren’t being hired hires annually to reach parity with the at the rate needed to establish parity in Ph.D. pool. It’s just arithmetic.” basic science departments (1). Gibbs earned his bachelor’s degree “My goal is to use data to demon- in biochemistry at the University of strate clearly and quantitatively that Maryland, Baltimore County, and there’s a robust talent pool of scientists his Ph.D. in immunology at Stanford from underrepresented backgrounds. University. He became a science policy We can stop having conversations fellow for the American Association based on the idea that scientists of for the Advancement of Science, com- color don’t exist,” says Kenneth Gibbs pleted a postdoctoral fellowship at the Jr., the lead author of the paper. National Cancer Institute, and then As a program director at the joined the NIGMS. National Institute of General Medical For the paper, Gibbs teamed up Sciences in the Division of Training, with Jacob Basson, a biostatistician at Workforce Development and Diver- the NIGMS; Imam M. Xierali, who sity, Gibbs isn’t in the business of manages the American Association of advising faculty hiring committees or Medical Colleges’ diversity programs; department administrators. But the and David Broniatowski, an assistant model he and his colleagues devel- professor who directs the Decision oped spells out for hiring managers Making and Systems Architecture what they have to do, collectively, to Laboratory at the George Washington establish a national faculty body that University. reects the talent pool and comes ASBMB Today’s executive editor, closer to reecting the American Angela Hopp, talked to Gibbs about population. his interest in workforce diversity, his “If two-thirds of the medical team’s ndings and obstacles to achiev- schools hired and retained one faculty ing parity. is interview has been

18 ASBMB TODAY MARCH 2017 edited for length, style and clarity. When and how did you get You wrote once about how started in this line of work? I was an AAAS policy fellowship the metaphor of the STEM for two years at the National Science pipeline doesn’t stand. Why Foundation in the Directorate for Education and Human Resources don’t you like it? in the Division of Human Resource I appreciate where people are Development. I got interested in trying to come from. ere is a clear understanding what was happening with me and my peers as it related to educational pathway to scientic inde- our career development. pendence. (Common wisdom is that) I was in a number of dierent the only way you get more scientists meetings where I was hearing talk PHOTO COURTESTY OF KENNETH GIBBS of color in the end is to stu more at Kenneth Gibbs Jr. about young scientists broadly and the beginning. at would lead you young scientists of color particularly to believe that workforce diversity that did not seem to match my own challenges are mainly about a lack of life experience. I also recognized, as a diversity early on, but empirically that scientist, that questions such as “Why doesn’t work out. Moreover, even if we do Ph.D. scientists make the career had a clear pipeline, current conversa- decisions they do?” and “How do the tions about this topic often ignore the decisions dier across demographics?” shearing forces that are inside the pipe. can be addressed empirically. When training environments and climates do not support all trainees, You were hearing including minority trainees, that is a shearing force that we need to change. people say what in those Also, I really don’t like the notion meetings? of leaking, as it takes agency away from people. I did not leak out of One was that (scientists of color) any path. I actively made decisions didn’t exist. at didn’t align with my about my career. I work in science experience. I look in the mirror every policy, as do many contemporaries day and see a black man scientist. I see hundreds of them on Facebook. who are from well-represented racial Two, there was a conation of race backgrounds. When my white male and poverty. I grew up middle class. colleagues make a choice similar to I’m an “n” of one and recognize that a mine, it’s not referred to as “leaking,” fair number of peers had greater prox- but when people of color or women imity to economic struggle, but that’s choose a career outside of academia, denitely not the case for all underrep- we’re called “leaks.” I don’t like that. resented scientists. Nobody leaked. Everybody is mak- ere was also the idea that we were ing choices. To really get at workforce all at minority-serving institutions. issues, including diversity, we need to ese are great institutions. How- understand those choices and address ever, I had many underrepresented the root causes of those choices. colleagues at places like Stanford, Conversations about a “leaky Harvard, Hopkins and Duke. pipeline” take our attention away Specically, I had three black from what we have: a talent pool of women friends who completed their thousands of scientists of color. Let’s Ph.D.s at elite East Coast institu- acknowledge that reality and, as a tions and who had rst-author papers community, work to ensure we are in (the Proceedings of the National utilizing this talent pool. CONTINUED ON PAGE 20

MARCH 2017 ASBMB TODAY 19 CONTINUED FROM PAGE 19 humanity as a whole, so I pursued a career as a scientist. Academy of Sciences), Nature and Sci- I went to the University of Mary- ence. However, their graduate school land, Baltimore County, as a Meyer- experiences were so challenging and, ho scholar. I also had funding from frankly, hostile that at the end two the (Maximizing Access to Research of them said, “I’m completely out of Careers) program at NIGMS, and the science,” and the other one said, “I Howard Hughes Medical Institute. will do research, but I’ll never stay in I got a biochemistry and molecular academia.” is is a loss for all of us, biology undergrad degree and did my because these excellent scientists are Ph.D. in immunology at Stanford accomplishing at the highest levels of University, where I focused on inter- our eld, and they don’t feel there’s a sections of stem cell biology, signaling place for them within our system. biology and cancer biology, at which en there was one of my white point I had my existential crisis. male colleagues, probably one of the smartest people I’ve met in science, who chose to start a business instead You weren’t sure if you of pursuing academia. I began to wanted to stay at the wonder: Why is anybody doing what they’re doing? Are the reasons that my bench? white male colleagues are moving out Remember, I started doing research of science the same reasons as those as a high-schooler. My rst job was of these black women that I know? working in a lab. I worked in labs at Why are these postdocs staying for six the (University of North Carolina) to eight years to try to get a faculty and at Duke (University) and in the position? 10th and 11th grades. So I’d been I recognized that I could not doing research from the age of 15, and change everything, but we can illu- I nished my Ph.D. when I was 26. minate what is happening. Change I wanted to take a step back and see happens when people start thinking if this was what I wanted to be doing. about the world dierently. I decided I can do it, and I enjoy it. But is it a I’m going to research it. thing that I really want to be doing? is was before the distress in the Tell me about your own Ph.D. workforce was en vogue to talk about. I completed grad school from education and career path. 2005 to 2010, so this was before it I am a black American whose was widely known. But observation- family has been here for centuries, ally, I could see something weird was meaning slavery and Jim Crow are happening around people getting jobs. part of our history. My grandfathers People were doing postdocs for seven had fourth- and eighth-grade educa- years, with Cell papers, and not get- tions, and my grandmothers both had ting jobs. high school diplomas. My mother and father were the rst people in their At that point you took the families to graduate from college, and that set up a worldview for me in AAAS fellowship, which set which education was very important. you off on this policy route. I grew up in Durham, North Carolina, the Research Triangle Park. e more I explored, the more I I did lots of internships in high school kept coming back to these really com- and got really hooked on the idea of pelling workforce questions. scientic research and what scien- I paired with a colleague of mine, tic research can do to be helpful to Kimberly Grin, who is an education

20 ASBMB TODAY MARCH 2017 researcher at the University of Mary- intervention strategies in the short and land. My goal has been to quantify the long term. qualitative aspects of our enterprise, We used the NSF Survey of Earned because scientists respond to num- Doctorates, which (the Federation of bers, not quotes. We started writing American Societies for Experimental papers and got some support from Biology) very nicely compiles every the AAAS’s education unit and the year on Ph.D. production (5), and Burroughs Wellcome Fund, and we’ve the AAMC faculty roster for faculty written a series of papers on biomedi- data (6). In 1980, there were 93 Ph.D. cal workforce development (2–4). graduates from underrepresented backgrounds, and that had grown to Given that you felt the 868 by 2013. And in 1980, there were 132 assistant professors from under- pipeline metaphor was represented backgrounds in basic science departments, and that grew to inadequate, did that play 341 by 2014. into your decision with this We see similar trends for scientists from well-represented backgrounds eLife paper? — that is, both populations grew. Yes, exactly. I was thinking about But then you see that from 1980, the it as a system instead of a pipeline. underrepresented student population Where do people move in and out, has grown 9.3-fold, whereas the pro- and what are points of leverage that fessor population has grown 2.6-fold. can help achieve certain outcomes? e rate of growth for underrepre- From an NIH perspective — again, sented Ph.D. (holders) is much greater not a policy perspective, but just a fac- than it is for underrepresented faculty. tual reality — most of our money goes to medical colleges. And so biomedical Already, you could see that workforce diversity is linked to faculty diversity in those specic contexts. I the pool is not depleted also gured examining these environ- of underrepresented ments could help illuminate what’s happening in other contexts, because scientists. many scientic environments have What we see is that the pool of these challenges. We focused on medi- scientists from underrepresented cal schools because of access to high- backgrounds has grown almost eight- quality longitudinal data. fold in the past 30 years, compared with two-fold growth for the well- Which brings us to represented candidates. e sizes of the pools are dierent by an order of your findings. magnitude, but, all things being equal, We wanted to know what actu- as the pools grow, you’d anticipate ally has been happening over the comparable entry into these faculty past 30-plus years — from 1980 to positions. at’s not what we see. 2014 — as it relates to (1) Ph.D. What we see is that for scientists production among scientists from from well-represented backgrounds, as underrepresented and well-represented the pool grows, more people are hired. backgrounds and (2) progression But there’s statistically no relationship into assistant professor positions in between the size of the talent pool for basic science departments. We then underrepresented scientists and the used these data to build a conceptual number of assistant professors hired. model of the workforce and used the model to test the impact of dierent CONTINUED ON PAGE 22

MARCH 2017 ASBMB TODAY 21 CONTINUED FROM PAGE 21 some number that always is there. We wanted to know how many The number of additional people were over and above what would be expected with overall underrepresented system growth through time. Using candidates has grown real data, in 2014, 5.8 percent of the assistant professors were underrepre- but academe is hiring a sented minorities. And that would be smaller portion than it consistent with a 0.25 percent transi- tion rate of URM scientists. at is, used to. even though we’re doing a lot to grow e nine-fold growth in the num- the URM talent pool, it looks like very ber of underrepresented Ph.D.s and few of these people are transitioning the almost eight-fold growth in the into the faculty pool. underrepresented talent pool sug- gests that the collective action of the You also tested some community to focus on and build the underrepresented talent pool has had interventions, right? an eect. is rate of growth is much We used the model to test the larger than the growth of those popu- impact of three interventions in the lations in the country since 1980. short and long term. ese interven- What we’re seeing, though, is a lack tions were: focusing on building the of connection between the talent pool talent pool, increasing the number and academic hiring. Between 2005 of faculty positions available, and and 2013, there were close to 6,000 increasing the transition rate of under- underrepresented scientists who got represented Ph.Ds. onto the faculty Ph.D.s in the biomedical sciences, and market and their subsequent hiring. between 2005 and 2014 there were All the models showed the same six fewer underrepresented assistant thing. If we only focus on growing the professors. ere’s a disconnect that URM talent and let it grow expo- needs to be addressed. nentially, by 2080 we would have 73 percent underrepresented minority Ph.D.s but only 8.9 percent under- Now explain the model. represented minority faculty. e e logic of the model is this: You low transition rate means that even have some number of people who without active discrimination, the aspire to these positions. ey go into system operates in such a manner that the market. And then people are hired the URM talent pool is disconnected based on the number of slots available. from academic hiring. In our model, there is no bias To see if it was an issue of the in hiring. People are hired directly number of jobs, we added 100 new proportionately to their representa- assistant professor positions annually tion on the market. So, if there are starting in 2015. Even with exponen- 90 well-represented folks and 10 tial growth in the underrepresented underrepresented folks on the market Ph.D. pool, there’s still no impact. and there are 10 slots, nine go to the Finally, we examined the impact well-represented folks and one goes to of increasing the transition rate — an underrepresented person. that is, getting more URM postdocs Historically, there was some num- onto the market. is dramatically ber of people who would have become increased faculty diversity, because as faculty no matter what. ere were more URMs enter the market, more minority professors in the 1970s when are hired. You only get diversity in the things were really terrible. ere’s faculty if you get people into the mar-

22 ASBMB TODAY MARCH 2017 ket and hire them. Changing the pool changes in the world. It is possible, or the labor market are not sucient though it will take changing the way to increase diversity. We have to think we’ve always done things. about transitions and hiring. Ultimately the goal is to enhance scientic excellence through diversity. Bottom line? If large sections of the workforce are disconnected from academic science, Change is possible now. e reality scientic excellence suers. is paper is that there are about 1,000 assistant focused on scientists from underrep- professors hired every year across the resented backgrounds, but many of country. If you hire around 1,000 peo- these issues also apply to women from ple a year, and you want 10 percent well-represented backgrounds. to be people from underrepresented backgrounds, which would match the Ph.D. pool, then that would mean You are careful not to hiring 100 underrepresented minority call your projections as assistant professors a year. We graduate close to 900 (under- “quotas.” represented) Ph.D.s a year. Correct. It’s a mathematical reality All of this is to say that we some- that it takes around 100 scientists times talk about issues of diversity as from underrepresented backgrounds if they cannot be xed. is can be each year to reach parity with the solved with around 100 people. Ph.D. pool. We assumed (in the past) that growing the talent pool would be sucient to right the system. is You’re not making, then, (paper) calls that into question. It recommendations. speaks to the need, I think, to recog- I am describing reality with the nize that this is happening and then hope that we can have a broader that there can be systemic architec- conversation in the scientic com- ture issues going on that are outside munity about how we ensure that we of the motives of any individual can eectively utilize the diverse talent person’s heart. ose issues need to pool that we have before us. be addressed so that this disconnect doesn’t continue. Medical schools could How hopeful are you that commit to doing this, if institutions will do this? they really wanted to. I believe that it can be done. We I think it’s important for all actors live in an interesting cultural moment. in the system — individual scientists, Science is not immune from the institutions, funding agencies, scien- broader societal challenges as they tic societies — to think about how relate to issues of race, and lots of they can individually and synergisti- institutions are examining if their cally work to address the issues that practices are keeping up with broader have been illuminated by this paper.

REFERENCES 1. https://elifesciences.org/content/5/e21393. 2. https://www.ncbi.nlm.nih.gov/pubmed/24297297. Angela Hopp ([email protected]) 3. https://www.ncbi.nlm.nih.gov/pubmed/25493425. is executive editor of ASBMB Today 4. https://www.ncbi.nlm.nih.gov/pubmed/26582238. and communications director for 5. https://www.nsf.gov/statistics/srvydoctorates/. ASBMB. Follow her on Twitter at www.twitter.com/angelahopp. 6. https://www.aamc.org/data/facultyroster/.

MARCH 2017 ASBMB TODAY 23 FEATURE Meet Anne-Claude Gingras One of the two new deputy editors for Molecular & Cellular Proteomics, she is a signaling soothsayer and candid Québécoise By John Arnst

nne-Claude Gingras is a senior mass spectrometry. In addition to her investigator at the Lunenfeld– role as a senior investigator, she is a A Tanenbaum Research Institute director of the institute’s proteomics in . Gingras started her lab group. is past fall, she and Steven at the institute in late 2005 and has A. Carr at the Broad Institute became won several awards for her research deputy editors at the journal Molecu- involving signal transduction and lar & Cellular Proteomics, where the current editor-in-chief is Al Burlingame at the University of Cali- fornia, San Francisco. Gingras spoke with John Arnst, ASBMB Today’s science writer. e interview has been edited for clarity and length. What are the projects that your group is working on? My research is mostly focused on understanding how proteins essentially associate with one another to perform their activities and how these associa- tions are perturbed by changes in the signals PHOTO COURTESY OF ANNE-CLAUDE GINGRAS that the cells would Anne-Claude Gingras receive. I’m also a full

24 ASBMB TODAY MARCH 2017 professor at the University of . because in Montreal, you can still live in French and work in English. I did What was your research my Ph.D. with Nahum Sonenberg. Nahum’s lab had discovered the inter- training? nal ribosomal entry site that many I did my Ph.D. at McGill Univer- viruses use to initiate the translation sity in the department of biochemis- of their own proteins. He had also dis- try. I worked on translation initiation. covered and cloned eIF4E, the protein I was characterizing how a certain that binds to the cap structure of the translation inhibitor called 4E-BP1 cellular mRNAs. was able to receive signals from the At the time when I joined, the lab insulin and growth receptor pathways had just cloned the rst two inhibitors to regulate translation initiation. is of translation that block the action process is involved in dierent cancers of eIF4E. Arnim Pause, the student and neurodegenerative diseases, and who cloned it, was leaving for his it’s also targeted by viruses. postdoc. I was lucky. I walked in the I graduated in 2001, and I started lab, and they said, “OK, new girl, my postdoc in 2002. I wanted to do your job is to nish the experiments more of a technical postdoc, as I had for that paper that we’re going to be a pretty good basis in fundamental submitting.” ey submitted it to biochemistry. I decided go to the lab Nature a few weeks after I started in of Ruedi Aebersold, who, at the time, the lab. When the paper came back, was in Seattle. Ruedi was a rising star I had to help with the revisions, so I in proteomics. Now he’s at the top of got to be on a Nature paper within a the world. He had just published a few months. It was really cool, and it proteomics method called ICAT that was super motivating. Of course that enabled researchers to compare the didn’t happen every week after that. abundance of peptides in two samples. One of the things that I learned What I wanted to do was to continue from Nahum is if you have somebody to work on the characterization of in your lab who’s good, you need to signaling pathways that impinge on let them come up with their own ideas translation but bring a proteomics and try them, because any given per- component to it. I started in Ruedi’s son will only have a limited number lab in 2002, and I worked there for of good ideas. Nahum would leave the just over three years. students and postdocs to essentially come up with crazy ideas and test them. What made you choose We had a case where we needed science as a career? to map phosphorylation sites. ere was this new professor at the time in I did my bachelor’s (degree) in Vancouver, who was Ruedi. (Author’s Quebec City at the University Laval. note: Ruedi Aebersold was at the It was in biochemistry. I worked in University of British Columbia from the lab one summer before the school 1989 to 1993.) We sent him some of year, and I realized I wanted to do our samples to do Edman degrada- research as a career. e mentor whom tion, and that’s how I got connected I had in the lab, André Darveau, (with Ruedi). We then collaborated was fantastic and spent a lot of time on several projects, eventually using training me. He’s now the dean of mass spectrometry to study phos- the science and engineering faculty at phorylation of 4E-BP1 and other Laval University. proteins. at got me very interested After that, I realized that I prob- in proteomics, and I knew I really ably should learn English. I thought McGill was a good compromise, CONTINUED ON PAGE 26

MARCH 2017 ASBMB TODAY 25 CONTINUED FROM PAGE 25 cell biology and so on. And, of course, I was an author. I have several papers liked Ruedi personally, so the deci- in MCP. sion to do my postdoc there was quite natural. I never applied for any other postdoc position, never went to an What was your reaction interview or anything like that, so it’s when they asked you to quite unusual in that way. I felt like that was the right thing for me to do take over? at the time. It caught me a little bit by surprise. My initial reaction was that I didn’t Do you have any words of want to have any more work, but then I thought, “Yeah, I have some ideas wisdom or a favorite motto of how to improve the journal. is for scientists in training? is the best journal in the eld, and it’s important for proteomics that people ere is one thing that I tell them: actually get involved and agree to step Be nice to everyone, because this is a up and contribute.” very small world. If somebody needs help, try to guide them the best way you can, whether it’s somebody in Do you have any hobbies, another lab or elsewhere. It’s going to or advice for balancing life be these people coming back in your life later on. in the lab with life I think when people join a lab after outside it? doing a Ph.D., sometimes they’ve been in a place where they were told to be My signicant other is also a sci- selsh. It’s such a collaborative world entist running his lab. If anything, he right now. e sooner you learn to works more than me. We don’t have a be nice to people and work well with super balanced life. We do things like people and to share everything — the hiking, but we don’t have kids, so that credit for intellectual contribution and makes it easier for me to commit to reagents — everybody wins. something else. at’s something that I fully realize is hard for some of my lab members with families. How’s the new role at MCP I give a lot of courses, seminars and going so far? conference presentations abroad, so I travel several times a month outside of Having Steve and me joining at the Toronto. same time is really good, because it enables us to re-energize and rethink the structure of the journal. Al has What’s the most interesting been really open to work as a trio of place you’ve traveled to in editor-in-chief and deputy editors, so it’s been great so far. I think it’s going the last year? to keep getting better. Just a couple of weeks ago, I was in southern Chile in this nice area that’s What was your involvement north of Patagonia, with this beauti- ful volcano and lake. It was spring with MCP prior to this? there, and it was beautiful. It’s a nice John Arnst ([email protected]) is I was one of the most used review- opportunity when you’re a scientist to ASBMB Today’s science writer. Follow him on Twitter at twitter. ers on the editorial board. I was travel to a lot of cool places, but it’s com/arnstjohn. dealing with a lot of the papers that something that most people who have had to do with protein interactions, a normal job don’t get to do.

26 ASBMB TODAY MARCH 2017 MARCH 2017 ASBMB TODAY 27 FEATURE Meet Steve Carr One of the two new deputy editors for Molecular & Cellular Proteomics, he advises “to be in a eld that is at the intersection of at least two dierent areas” By John Arnst

teven A. Carr, director of the What was your background Proteomics Platform at the S Broad Institute of MIT and and research training? Harvard, became a deputy editor at I did my undergraduate work at the journal Molecular & Cellular a college in upstate New York called Proteomics along with Anne-Claude Union College. I was a chemistry Gingras at the Lunenfeld–Tanenbaum major, and I thought I was going to be Research Institute in Toronto this past an organic chemist, so I went to (Mas- fall. Carr has been an associate editor sachusetts Institute of Technology) for with the journal since its inception graduate school and began work in a in 2002. e journal’s editor-in-chief laboratory doing organic chemistry is Al Burlingame of the University of with Klaus Biemann. I then did a postdoc with Vernon California, San Francisco. Carr spoke Reinhold at Harvard Medical School. with John Arnst, ASBMB Today’s I realized that mass spectrometry’s science writer. e interview has been primary use at the time was for analyz- edited for clarity and length. ing post-translational modications. e most dicult of those at the time Tell us about the work was glycosylation. It remains probably one of the more dicult areas of post- you’re doing. translational modication to make any e research in my lab focuses on headway in. developing and applying technologies I left Harvard Medical School to go to quantify proteins, their modica- to what was, at the time, Smith, Kline tions, and their interaction partners & French laboratories down in Phila- in stages of health, disease and other delphia. ey were just beginning perturbation conditions. We do that to acquire very signicant amounts work to try to understand the func- of money from their H2 antagonist, tion of the proteins and their response Tagamet, which became, I believe, the and resistance to drugs. rst billion-dollar drug on the market. My group also has a major focus on ey were building a huge facility out in King of Prussia, Pennsylvania. ey discovery and quantitative verication were an old, sleepy pharmaceutical of biomarkers for major diseases, such company, but they hit on Tagamet, as cancer, cardiovascular disease and and they basically decided to com- infectious disease. We put a lot of time pletely revitalize and reorganize the and eort into pushing new technolo- company. gies in that area as well. Hepatitis B vaccine was the very

28 ASBMB TODAY MARCH 2017 PHOTO COURTESY OF STEVEN CARR Steven Carr rst thing that I worked on when I again for me, so in many ways it was went there, and it was really a thrilling setting me up for failure further on. process. I went back and forth from Many disappointments in projects Philadelphia to Ricksonfort, Bel- occurred after that point and taught gium, where our vaccine aliate was me that research is really hard and located, and was involved in all of the failure is the most common thing that initial characterization work of that you’re going to have to learn to deal vaccine product. What was very inter- with. And keep your chin up. esting was that protein was extremely hydrophobic. Is there any advice you Mass spectrometry was ideally suited for this. We covered a very would give to young high percentage of the protein in our scientists? regulatory ling, and it really helped the company get the vaccine on the ere are two pieces of advice. One market when we were in hot competi- is that it’s really important, if you can tion with Merck. It turned out to be a manage it, to be in a eld that is at the big product for the company, partially intersection of at least two dierent because the World Health Organiza- areas. Mass spectrometry was kind of its own specialization, but applying tion came around and said that all mass spectrometry in biotechnology children have to be vaccinated with was that junction. It just makes you a hepatitis B vaccine. at helped both lot more valuable (as a researcher) and Merck and Smith Kline. provides the most interesting problems at was maybe an unexpected to work on. e other piece of advice and unusual win for a drug company is that life’s long and work is a huge at that time, because it was a very part of what you do, so you better care fast timeline from the start through to completion. at never happened CONTINUED ON PAGE 30

MARCH 2017 ASBMB TODAY 29 CONTINUED FROM PAGE 29 What was your reaction about what you do; otherwise, change like when you were asked what it is you’re doing. to be a deputy editor? What made you want to I was honored, of course, and felt empowered to speak up at an even become a scientist? greater level than I had previously. It’s I credit my parents. Neither of a pleasure working with Al and Anne- them had a high-school education. Claude. I think that we’re a terric ey were forced as a result of the team, and we’ve gotten o to a great start. Depression to leave school and go to work. ey impressed on me that I had to get an education. We ran a Between your lab work and television repair shop out of my par- your MCP duties, what do ents’ house where I lived in Putnam Valley, New York. I did work in that you do outside of the lab? shop alongside my father and learned I have done a lot of woodworking a fair amount about electronics. He in my time. I haven’t been able to do was entirely self-taught. ose were as much lately, but I still consider that the sort of things that rubbed o on a hobby. I am a scuba diver. My son me — the general curiosity about how and I, whenever we have the chance, things work and why and this push go o to some exotic location and go toward education. Chemistry was diving together. We’ve gone to Bonair originally the thing I wanted to do several times (Author’s note: Bonair more than anything, partly because I is in the southern Caribbean). We’ve had chemistry sets when I was a kid gone to Hawaii. e South Pacic, and did a lot of fooling around in the specically Palau, is on the bucket list. basement with them. at area is fantastic not just because When I went o to college, there the coral is still reasonably intact in were a couple of really good profes- those areas but because there are a lot sors at Union College that took a of wrecks, unfortunately, from World special interest in me. ey helped me War II. e wreck diving there is understand that I could actually apply really, really good. to graduate school, I could go beyond just getting a college education, I Do you have any advice for didn’t have to go out immediately and try to get a job after college. balancing your life in the lab with life outside of it? How is the new role at MCP Balance is denitely the wrong going so far? word. I think it’s more like a teeter- totter. You sit on the work end, you I think it’s going well. I feel hit the ground and you’re sitting there empowered a bit more to help make for a while, laboring away at work, decisions and move the journal for- and suddenly you realize that, wait a ward into the future. ere’s a number minute, that other part of your life, of things that are still under discussion which is the other end of the teeter- that I think are going to make MCP totter, is up in the air and you haven’t John Arnst ([email protected]) is even more attractive to the commu- ASBMB Today’s science writer. dealt with it. You have to rebalance. I Follow him on Twitter at twitter. nity of proteomics scientists as a place go traveling with my wife, and I go for com/arnstjohn. to publish. ose will get rolled out in long hikes with her. at’s how I try to the not-too-distant future. provide some balance.

30 ASBMB TODAY MARCH 2017 EDUCATION

Starting the organelle wars By Bradley Graba

IMAGE COURTESY OF ANDIE EVANS, A SENIOR AT WILLIAM FREMD HIGH SCHOOL

n 2011, I was looking for a way to ence teacher and department chair, average ACT score of 25 and, most invigorate teaching cellular organ- and my brother is a physics teacher importantly, they are motivated, I elles to high school freshmen. and head of the math and science respectful kids who are fun to work I am lucky enough to teach at Wil- department at Crystal Lake South with. e overwhelming majority liam Fremd High School in Palatine, High School in the Chicago suburbs. of our parents are supportive and Illinois, which is about 45 minutes e community teachers and stu- involved in their kids’ education. I northwest of Chicago. For me, teach- dents are proud of our school, where myself graduated from Fremd in 1994 ing is a family aair. My mom was a 97.1 percent of our students graduate and then was hired back to teach there third-grade teacher for most of her and 84.3 percent of our students are in 1998 after graduating from Illinois career, my dad was a junior-high sci- college-bound. e students have an CONTINUED ON PAGE 32

MARCH 2017 ASBMB TODAY 31 of the students, I did not hear any complaints from students or parents about creating the account. In addi- tion, because the use of social media fell in the extras category, students could fulll the requirement for that category of the project without using Twitter if they or their parents were not comfortable with the idea. e reason for adding the twist was pretty simple. My students were always on their phones and on Twitter anyway, so why not take the project to where my students were spending a lot of their time? e use of Twitter put the project over the top. In 2011, Twitter wasn’t as powerful as it is today. My students followed each other’s accounts, and I followed them all to monitor the accounts. Everything stayed within the small circle of students in my class. e next year was an entirely dif- ferent story. It was an election year with President Barack Obama running for re-election against Mitt Romney, so the class was already buzzing with a little more excitement than usual when it came to campaigning. On the rst day of the project, one of my groups mentioned that someone they didn’t know was tweeting at them. Being relatively new to Twitter at the CONTINUED FROM PAGE 31 I immediately fell in love with the idea time, I was concerned as to who might Wesleyan University with a bachelor’s of having my students run a cam- be interacting with my 14-year-old degree in biology with a minor in paign. e wonderful part of the proj- students. It turned out that the person secondary education. ect was that students not only had to tweeting them was a researcher from I was struggling to teach the promote their own organelle but also England who specializes in study- unit on cellular organelles, because had to run a smear campaign against ing the Golgi apparatus. Her name the unit can be a tough one to get ve other organelles. is requirement is Anne Osterrieder from the Oxford students excited about. I had tried served the purpose of making sure that Brookes University, and she had been more cell-organelle projects than I the students learned about more than searching for information about the cared to count over 13 years. So, in just their own organelle. Golgi apparatus on Twitter when 2011, like most resourceful teachers, One of the other requirements of she came across my student’s Twitter I went to the internet to nd inspira- the project was that the students create account. tion. ere, I came across a project extra campaign materials, such as i- At that point, the project exploded. by Marna Chamberlain at Piedmont ers, shirts and bumper stickers. Here, Osterrieder and her colleagues began High School in California that piqued I added my own twist to the project. I tweeting with my students’ organ- my interest. encouraged the students to take their elle accounts, prodding them with Chamberlain had her students campaign to social media by creating higher-level questions, holding them complete a project that involved Twitter accounts for their organelles. accountable for spreading misinforma- campaigning for a cell organelle to be Since each account was in the name tion, and engaging them in a way that elected the most important organelle. of the organelle and not in the name my students had not expected from

32 ASBMB TODAY MARCH 2017 IMAGE COURTESY OF ADHITH PALLA, A JUNIOR AT WILLIAM FREMD HIGH SCHOOL a freshman biology project in high improved as the project continued, to their tweets about the number of school. as did their knowledge of the struc- people supporting them as well as the Soon we had scientists from around ture and function of all of the cell’s use of monikers. e trends of the England, France and the U. S. tweet- organelles. 2016 election denitely made their ing with us. One of those scientists, Over the past four years, one of way into our classroom election. John Runions, also of Oxford Brookes the big changes I have made is that e #organellewars project has University, has his own BBC radio I have required that smears of other changed the way I approach teaching show under the persona of “Dr. Mol- organelles not be related to diseases high-school students about cellular ecule” and discussed our project on his that are caused by problems with the organelles. It allows my students show. Runions also is the person who organelle. I found that students spent to interact with scientists who are developed the #organellewars hashtag. time researching the names of diseases experts in cell biology. It holds them One of the main outcomes of the that were caused by organelles but accountable for learning about their project was that my students real- were not focusing on the specic role organelles, and it injects an element of ized that what they tweeted was of the organelle in the disease. Now fun and excitement into my classroom going to be fact-checked. ey began the smear campaigns must relate to that had been missing with other cell- using Google Scholar and citing the structure and function of each organelle projects. their sources, because they had a live organelle, not the diseases it causes. and knowledgeable audience watch- e smear campaigns denitely ing their every move. e quality of have become more useful in terms Bradley Graba ([email protected]) is a high information being produced by my of student learning. is year, it also school science teacher. Follow students about their organelles and was interesting to see the number of him on Twitter at twitter.com/ the ones that they were smearing made-up statistics students would add mr_graba.

MARCH 2017 ASBMB TODAY 33 DUE DILIGENCE Pixel perfect By Kaoru Sakabe

hen the results started rolling arranged in an x, y grid such that the in and a story began emerg- nal image will show coimmunopre- W ing, my thesis adviser usu- cipitation of your protein of interest or ally instructed us to start assembling mislocalization of your protein upon gures for a paper. At rst, it was treatment with an inhibitor. daunting to see blank gure panels e resolution of the image refers nestled between the data we had. But to the density of pixels. It is the the process made it easier to identify number of pixels that make up your missing experiments and to see the image. e greater the resolution, the logical progression of the story as the more information an image contains holes started to ll in. and the clearer your image will be. With so much attention focused on is quantity is expressed as pixels per e lm you have scanned, the immu- building a scientic argument, the last inch, or ppi. For publication purposes, nouorescent image you’ve snapped thing on my mind while assembling most journals will require that you or the Western blot image you’ve gures was the nal gure resolution. submit your nal gures with a mini- exported from an imaging system — However, forgetting to keep resolu- mum resolution of 300 ppi. You often that image is composed of many pixels tion in mind from will see dots per inch, or the start can cause dpi, used interchangeably problems later on. To with ppi, but dpi actually avoid any potential refers to printer output, issues down the road, or how many dots of ink I oer a few tips. are found per inch of a Let’s start o with printed document. Since some basics. When we are talking about digi- reading submis- tal images, ppi is the more sion guidelines for relevant term to use. journals, they often e last bit of informa- throw around terms, tion you need to know such as “minimum is that your image data resolution,” “dpi,” can be either raster or “ppi” and “vector vector data (Figure 1). graphics,” which all Raster data is simply an seem irrelevant when image made up using you are eager to write pixels as building blocks up your manuscript. as discussed above. Vec- So what is a pixel, the tor data, on the other rst “p” in “ppi”? A hand, is not composed of pixel, derived from pixels but rather is a set “picture element,” of instructions that tells refers to the most the computer to display basic unit composing lines and curves. is an image. Each pixel type of data is useful for contains information graphs or models, since it telling the computer remains smooth no matter what color or shade Figure 1. Raster data vs. vector data. Raster data becomes pixelated as you zoom in, whereas how much you zoom in. of gray to display. vector data remains clear. Conversely, raster data

34 ASBMB TODAY MARCH 2017 Figure 2. Resolution matters! Even if you scan your film at 300 ppi, if you use PowerPoint, you effectively are changing it to a 72 ppi image. becomes pixelated as you enlarge the Tip 2: Use appropriate software journal. Most journals provide two image, making the gridlike pattern of when laying out your gures. Power- or three size options: single-column pixels obvious. Point may be user-friendly, but it is width, double-column width and OK, we’ve got the basics. Now how meant to work at screen resolution, occasionally 1.5-column width. Once do you apply this information to cre- which is only 72 ppi. When you you insert your graphics into the ate awesome gures? export images from this program, you gure using the appropriate software, Tip 1: Remember that gure end up with a 72 ppi image that needs you usually don’t have to worry about preparation begins at data acquisi- to be converted into a 300 ppi one image resolution; however, be careful tion. Make sure you are acquiring (Figure 2). Conversion to a higher res- when increasing the size of a raster your image at the proper resolution. olution image can result in an image image. If you insert a 300 ppi image Whether you are scanning a lm or that is too small for publication or one and decide you want to double its size, exporting a le from an imaging sys- that is extremely pixelated. Addition- the resulting resolution of that image tem, keep the minimum resolution of ally, depending on how you upscale, will be 150 ppi and likely will look 300 ppi in mind. It’s never fun when or increase the number of pixels in less clear than the original. you realize that you have to nd a your image, your software program Keeping track of image resolution particular lm to rescan at the proper may introduce pixels into your image, shouldn’t be a hassle. By incorporating resolution months (or even years) after thereby creating artifacts. Adobe these suggestions into your workow, you performed the experiment, or Illustrator usually is recommended you can rest assured you have done worse, conduct the experiment again for gure assembly, but Inkscape and if you can’t nd it. For graphs, make CorelDraw are good alternatives. your due diligence. sure you are exporting the data in ese programs are meant to combine nonraster format, such as *.pdf, *.eps raster and vector data into a single Kaoru Sakabe or *.svg. Exporting in these types of gure and can do so without aecting ([email protected]) is the data formats will prevent your graphs from the pixels found in raster data. integrity manager at the ASBMB. looking pixelated and keep text legible Tip 3: Set your canvas size to the no matter how you resize it later. physical dimensions provided by the

MARCH 2017 ASBMB TODAY 35 OUTREACH Effective communication: dream or reality? By Geo Hunt

cience communication.” wrote the report. At the hearing, Biology will take is to start publishing It is a phrase that is both Leshner stressed the timeliness of the the broader impacts of their work. “Scelebrated for its importance report, emphasizing how eective Any researcher applying for funding and reviled for its ambiguity. Scientists communication is necessary to ensure from the National Science Founda- are encouraged to communicate often that science continues to play a vital tion has to include a description of and eectively to help gain support for role in current events. Committee vice how he or she will demonstrate the their research. At the same time, there chairman Dietram Scheufele, profes- broader impacts of the proposed is extensive debate among science- sor at the University of Wisconsin– research on society at large. Unfortu- communication researchers and Madison, pointed out that the report nately, researchers rarely publish these professionals about what communica- was particularly relevant for the new types of results. When they do, the tion is, what the goals are for dier- generation of scientists who are more publications usually are conned to ent communication eorts and what comfortable with communicating to education-focused journals, thereby approaches are most eective. broad audiences than previous genera- bifurcating the scientic research and So it was with great fanfare and tions but who still need direction on science-education communities. anticipation that the National Acad- how to do so eectively. e ASBMB Public Outreach emies of Sciences released a report in Despite the optimism exuded by Committee wants to bridge this bifur- December titled “Communicating the authors, several within the com- cation to help connect scientists and Science Eectively.” Stakeholders munity remain unconvinced. Rick science communicators. We are look- hoped the report would provide clarity Borchelt from the Department of ing to collect and disseminate descrip- on best practices in science communi- Energy Oce of Science asked during tions of broader impact activities that cation and illustrate a path forward for the hearing what the report added stem from research publications. Our the eld. to the eld of science communica- motivation for this eort is straight- Unfortunately, little within the tion, citing publications going back forward: to provide ASBMB members report points toward immediately at least 15 years that made similar with outlets that will help them com- actionable suggestions. Instead, the recommendations about doing more municate their science. If you have main takeaway is that more research is research into eective communica- published an NSF-funded research needed into several questions related tion approaches. Other commentators paper within the past 12 months and to science communication: How do also wondered aloud what agency or want to share your broader impacts social factors inuence trust in sci- institution would fund the ambi- story, send us a message at ence? How can (and should) science tious research agenda. To generate [email protected]. aect policy debates? What is the momentum from the report, the e more we can generate buy-in best way to communicate scientic NAS announced that it will host the and support within the research com- controversies? “Science of Science Communication” munity for science communication, Looking to obtain more informa- colloquium in November to explore the stronger the argument becomes tion about the report’s intention and these issues further. that communicating science eectively expected outcomes, several leaders But what can organizations and needs to be a standard part of the within the science-communication individuals do to help advance the scientic process. eld gathered in January for a public cause of science communication? hearing with the report authors in While nowhere near as ambitious as Geoff Hunt ([email protected]) Washington, D.C. e CEO emeri- the research agenda laid about in the is the ASBMB’s public outreach tus of the American Association for NAS report, one small step that we manager. Follow him on Twitter at the Advancement of Science, Alan hope members of the American Soci- twitter.com/thegeoffhunt. Leshner, chaired the committee that ety for Biochemistry and Molecular

36 ASBMB TODAY MARCH 2017 ESSAY Is biochemistry a tool or a discipline? By Binks W. Wattenberg, Enrique M. De La Cruz & Daniel M. Raben

poiler alert! e answer to the the people who want to understand question posed in the title is the chemical details of life in all its S clear: It’s both. forms. It is important to be able to But the distinction is important. ask a colleague about the anity of a When asking this question to new substrate in an obscure reaction and to graduate students or some seasoned have that question taken as a serious investigators, it’s not unusual to hear challenge and not an annoying detail. them declare that biochemistry is We need a space where understanding “just a tool.” Indeed, biochemists have DNA repair in a deep-sea mollusk is developed methods and reagents that given the same weight as in a mam- are essential for other disciplines. But malian cell. biochemistry is more than just a col- proteomic and lipidomic techniques Maintaining biochemistry as a lection of techniques. As a discipline, and enzymatic assays to examine the discipline is essential to the progress biochemistry is characterized by the interactions of drugs or toxins with of all the biological sciences. We need mechanistic insights and predictive specic cellular components. ey the intellectual and physical space to power that it produces. would identify themselves, validly, as delve deeply into mechanisms. Time e confusion inspired by the ques- pharmacologists despite the biochemi- and again, these mechanisms have tion is partly due to the fact that, as a cal underpinnings of their studies. been shown to be broadly applicable. distinct discipline, biochemistry seems Strictly speaking, a biochemist is Biochemists develop the critical tools on the verge of becoming a victim of someone who studies the underlying to illuminate these mechanisms that its own success. is success is largely chemistry of biological processes and ultimately we will share with our due to technical approaches and intel- systems. Traditionally, biochemistry colleagues in dierent disciplines. As lectual discoveries that have cracked encompasses the study of the chem- biochemists, these tools are one of our major contributions to the broader questions of fundamental and clinical istry essential to biological processes biomedical research enterprise. If importance in biomedical research. including, but not restricted to, scientists want tools, they will want to Neuroscientists, immunologists, enzymes, metabolism and signal keep and respect biochemistry as an cancer biologists, structural biologists transduction. Importantly, the use independent discipline. and physiologists, among others, all of puried components and cell-free take advantage of these biochemical systems for these studies has been a approaches and discoveries. However, dening hallmark of the biochem- Binks W. Wattenberg, a lipid bio- this prompts the question as to who istry discipline. Dyed-in-the-wool chemist, is an associate professor in the department of biochemistry exactly is a biochemist and, relatedly, biochemists focus heavily on dening and molecular biology at the whether it makes sense to have a disci- the chemical mechanisms that drive Virginia Commonwealth School of pline devoted to biochemistry. the biology. ey don’t identify with a Medicine. Enrique M. De La Cruz For example, what is the dierence single biological system, even though ([email protected]) is a first-generation Cuban-American between a neuroscientist or pharma- they may have chosen to focus on one from New Jersey and a professor cologist using biochemical tools and for their studies. It is this mechanistic of molecular and bio- a biochemist working in a neuronal focus that denes the biochemistry chemistry at Yale University. Dan- system or studying a pharmacological discipline and has resulted in key iel M. Raben ([email protected]) is a professor in the department problem? is question highlights the intellectual discoveries and technologi- of biological chemistry at the fact that scientists often identify them- cal advances. Johns Hopkins University School of Medicine and a selves with the system they are study- It is essential to have a standalone member of the American Society for Biochemistry ing. Take the individuals who exploit community of biochemists. ese are and Molecular Biology Lipid Research Division.

MARCH 2017 ASBMB TODAY 37 ESSAY Working at Manylabs, an open science space By Gary McDowell

eaving the laboratory can also to explore a less conven- be a daunting prospect for tional workspace. My applica- L a variety of reasons, not in tion was successful. I am now in the least that the lab environ- my second six-month residency. ment itself can provide a unique Our space matches the stimulating experience, with stereotypical picture of a San people around you carrying Francisco cooperative working out experiments and discussing environment. We are housed in science. For this reason, when a warehouse on Folsom Street I decided to leave my postdoc- in the SoMa neighborhood, toral stint at Tufts University with desk space on the top oor, to begin working full time for desk and lab space on the oor Future of Research, known as below, and more lab space and FoR, and follow my husband a large workshop space on the to San Francisco, where he was ground oor. e workshop doing his medical residency, I space is a useful facility to have wondered what kind of working as I start to do more workshop/ environment I might end up in. meeting-based work with the It could have been at home or local scientic community. at a rented cooperative working e residents hold open house space. In moving away from events where we showcase our working at the bench, I could, work and give demonstrations as long as I had my computer, to the community. work pretty much anywhere, ere’s an incredible range but it was important to me to PHOTOS COURTESY OF GARY MCDOWELL of work going on at Manylabs. have a desk outside my home Cere Davis showcasing her artwork at Manylabs ere are people using science and be surrounded by other career outcomes, salaries, fellowships in art, groups installing air- and people. and training opportunities. We also water-quality monitors around the My boss, Jessica Polka, had passed are interested in fostering a scientic Bay Area, computational scientists along an opportunity she had spotted enterprise that recognizes, enjoys and creating open-source tools to map in a tweet for a residency in a unique benets from the diverse ways science food webs, organizations driving open working space called Manylabs. A can be practiced and used to con- data-based environmental advocacy, nonprot organization supported by tribute to society, and in nding out and groups working on local commu- the Gordon and Betty Moore Founda- more about the ways science happens nity outreach around natural history. tion, Manylabs aims to provide a space outside academia. Additionally, FoR is ere are those developing innovative that brings together scientists, educa- dedicated to helping junior scientists educational tools, such as kits for stu- tors and “makers” who are working on practice open science safely, making dents to build to learn a variety of sci- open-source tools for science. the data, research and educational ence and engineering lessons. ere’s Transparency is central to the resources they produce freely available a movement toward facilitating citizen mission of FoR. Our mission is to to improve transparency and assist in science in the lab spaces. Some of the make the research enterprise more reproducibility. erefore, Manylabs work of the people at Foldscope takes transparent to junior researchers by seemed like an ideal environment to place here too, in trying to distribute analyzing and providing data on maintain my comfort with the lab but aordable devices for science around

38 ASBMB TODAY MARCH 2017 Eric Mandu gives a lighting talk about an aquaponics system at the Manylabs Open House in October. the world. which is a reference to the comput- I travel a lot for my work now. I’ve As it’s usually billed as a maker- ing language, but instead we have tea been to Boston, New York, Edmon- space, I sometimes feel a little like an and discuss what is going on with our ton, Calgary, Chicago and Washing- imposter to be hanging around work- work. We also update the Manylabs ton, D.C., in recent months, but it’s ing on policy and advocacy, but at the website with monthly updates both great to have a home base and some- same time, everything that is happen- for the public and for each other. It’s where to keep my collection of frog ing here is also central to helping me also a chance to see how we can col- mugs from my lab days. Being in an understand the barriers to nonin- laborate with each other. environment where people are doing stitutional science and the dierent e major challenge for me has things that are very dierent from my incentive structures that are directed been moving from a hierarchical academic experience, where they all more toward local educational or envi- structure like academia into a very are looking to eect or advocate for ronmental eects than the traditional unstructured environment. No one change or educate the wider public, is publication structure of academia. technically is in charge. It has benets really refreshing and helps me in some Of course, the one thing that feels and downsides. But that soon will aspects of my work around advocacy. familiar is the search for funding. change, as the group has hired a com- I’m looking forward to holding more Being in a nontraditional space in munity manager to provide support workshops and satellite events around science means looking for nontradi- for the organization and the people conferences that are in town to con- tional funding sources or fundraising within it. Because we rarely are all nect with the local scientic commu- eorts. I am currently fortunate to together, it can be something of a nities. Manylabs has been helpful in be supported by a grant from the challenge for everyone to know what shaping my thoughts on the dierent Open Philanthropy Project. Some in everyone else is working on in great ways science and society could interact the space have to work elsewhere to detail. e inability to overlap in time and broadens my vision of a more support their nonprot work, so there and space may limit possible collabo- encompassing scientic enterprise. are people who I see through the day ration. However, it will be exciting regularly and some I hardly see at all, to have someone around all the time Gary McDowell depending on who has what kind of whose job is to know what is going on ([email protected]) is the support for their work and when they and what everyone is doing and to cre- executive director of the nonprofit can be around. ate connections within and outside organization Future of Research We get together weekly for “T++,” the organization. and a resident at Manylabs.

MARCH 2017 ASBMB TODAY 39 ESSAY Just like Boyd Gary Weisman is inspired by his 100-year-old mentor, Boyd O’Dell By Stephen Schmidt

n 1985, Gary Weisman now is the CEO of Scientist. had several assistant profes- com. I sorship oers in molecular Lustig, along with then- biology after nishing his graduate student Laurie postdoctoral fellowship at Erb (now an associate profes- Cornell University. He had the sor of biochemistry at MU), enviable problem of having cloned the rst human gene trouble deciding which oer to for a P2 nucleotide recep- choose. tor. For years, others in the “ ey said ‘Don’t dismiss biochemistry eld had doubts Missouri,’” says Weisman, about Weisman’s research, but recalling the advice from his not O’Dell. “No one thought Cornell colleagues. “ ey the receptor was real,” says knew Boyd O’Dell personally Weisman. “Kevin and Laurie and how big he was in the kept me on the straight and eld.” narrow, and Boyd was here all As the head of the depart- of the time mentoring me, and ment’s hiring committee for a I worked through the problem new cell-culture laboratory at and basically convinced every- the time, O’Dell, a professor of body that it was real.” biochemistry at the University Weisman, who lives about of Missouri, was fascinated by PHOTO COURTESY OF JUSTIN KELLY three blocks from O’Dell, also Weisman’s work with cell- O’Dell raises a glass of wine at an event honoring his 100th birthday. has adopted one of O’Dell’s culture models, which would He would go on to become one habits. For the rst 10 years of allow the institution’s researchers to of the rst scientists to discover the his time in Columbia, while driving speed up the work that initially was important role that folic acid and vita- to work every day, Weisman would being run with animal-based models. always see O’Dell walking to his lab. min B12 play in the development of Weisman ended up heading west to Inspired, Weisman started walking to human and animal embryos, leading help transition the work of faculty in campus in the 1990s. to the now-well-recognized relation- food science and nutrition at the uni- “I just saw how t he was. He ship between deciencies in folate versity into the realm of cell biology. was much older than me, but still he and B12 and birth defects in humans. was working pretty hard and walk- A pioneer in O’Dell, with the help of his research ing all of the time,” Weisman says of team, also discovered in the late 1950s O’Dell, who still makes his way to his nutrition research how phytic acid interferes with the laboratory on foot when the weather O’Dell, who turned 100 in absorption and utilization of zinc. is good. “So I changed my lifestyle October, has spent most of his career, “ at observation has caught and took nutrition more seriously and which dates back 80-odd years to worldwide attention, and they’re started walking. his time as an undergraduate stu- still researching it in humans,” says “To this day, I have not used my dent beginning in 1937, at MU. He O’Dell. car at all. I walk everywhere around worked primarily on animal-based Weisman, who became a professor town. Basically, I’m always on my feet nutrition research related to trace of biochemistry at MU in 1998, was following in Boyd’s footsteps. I don’t mineral deciencies, namely of zinc accompanied to MU by his top lab mean that in a general way. I mean and copper. assistant at Cornell, Kevin Lustig, who that absolutely literally.”

40 ASBMB TODAY MARCH 2017 PHOTO COURTESY OF STEPHEN SCHMIDT Boyd O’Dell (left) and Gary Weisman Forming a partnership cells to measure zinc released by a do tomorrow, and I think you’ll stay mild oxidizing agent. in the game longer than you think,” Weisman’s lab is in the same build- He adds the zinc back and releases Weisman says of his mantra. “Life ing where O’Dell does his research. In it again. Based on the results obtained, goes fast, but I just don’t see myself 2014, O’Dell received word that Weis- Camden has used similar conditions as a 65-year-old. I see myself as a man had a uorometer in his lab that to measure calcium uptake with the teenager. And I think Boyd must be would be perfect for his work on how uorometer. O’Dell and Camden that way. He must not see himself as zinc deciency harms cell function hope to publish their results soon. 100-years-old.” by blocking the signal for calcium “His hearing is the only problem, When people ask him about retire- uptake. O’Dell was put in contact so you talk loud,” Weisman says of ment advice, O’Dell provides two with Weisman’s head technician, Jean O’Dell. “But he’s still thinking just as words: “Keep working.” Camden. fast as we are — faster probably.” “Try to pick something that you’re “We’ve been working together passionate about and do it,” O’Dell ever since,” says Camden, who, like ‘Don’t worry says. “If you like to research, as I do, O’Dell, is now semiretired. In the fall that’s OK. If you think that you want of 2014, the two began the measure- about your age’ to spend your time making shing ment of calcium uptake with blood lures, that’s OK too. But you have to platelets before it was determined that Weisman, at age 65, has no inten- tion of slowing down and becoming be passionate enough to really want to the platelets had too short of a shelf get up and go.” life. e following spring, Camden inactive, although at the moment suggested they work with human T he cannot wrap his mind around Stephen Schmidt lymphocyte cells, called Jurkat cells, approaching 100. “Don’t worry about your age. ([email protected]) is a which can be produced easily millions science writer at the University of at a time. Worry about how you feel today. Missouri’s College of Agriculture, O’Dell has been using the Jurkat ink about what you’re going to Food and Natural Resources.

MARCH 2017 ASBMB TODAY 41 THE DO-OVER If I could turn back time By Eleftherios P. Diamandis

he rock icon Cher sang her the U.S. and bought a cheap hit of the 1980s “If I Could wooden racket from K-Mart T Turn Back Time.” How- before returning to Greece. It so ever, we all know that nobody happened that near my apart- can do this, and the Nobel ment in Athens there were two laureate Bob Dylan conrmed it university tennis courts where with his song “ e Times ey I could play tennis for free. As Are A-Changin.” the tennis courts were in high At the 2016 Annual Confer- demand, we usually had to wait ence of the American Associa- two or three hours to play for 30 tion for Clinical Chemistry, I minutes, as court booking was attended a session honoring not a thing in Greece during three very successful clinical that time. e balls we were chemists. I asked each of them using were beaten to death and of what alternative career they barely bounced. If the strings of would pursue if given a second my racket broke, I would mend chance. One kindly declined to them myself, since I had no answer. e second emphatically money to replace them. I would declared that he was completely try to hit tennis balls anywhere, satised with his current career including walls, inside my and would follow the exact same apartment or even in the lab path if he were to start over. e where I worked! I followed all third one, who enjoys athlet- the international tournaments ics, revealed that he would have and scores in newspapers (no pursued professional golf. internet then) and fell in love I believe that I have had a with the champions of the successful career in science and time, such as Bjorn Borg, John academia. I published often, McEnroe and Jimmy Connors. made some discoveries, men- When my children were born, I

tored more than 60 graduate PHOTOS COURTESY OF ELEFTHERIOS DIAMANDIS so desperately wanted them to students and collaborated with The poster for Diamandis’ laboratory band become Wimbledon champi- an army of other scientists ons that I even wrote a ction during the course of my career. explore when building a professional piece on this subject (1). To my e beauty of our profession is that career. Over the years, I have been disappointment, my children never we have the freedom to investigate devoting time and energy in areas really showed any interest in play- unanswered questions of our choice outside my profession. I suspect that ing professional tennis (they play for and be at the forefront of curiosity- these natural and spontaneous tenden- recreation) and I was never really good driven research. At the same time, we cies could have been used to build an at the sport either. Yet each of the two have the privilege of working with alternate career. From very early on, I properties I own includes a tennis brilliant young people whom we coach showed a keen interest in many sports, court, both built before the houses to develop their own paths to success. including soccer, boxing, basketball, were erected! (Important things rst.) It is a very rewarding and well-paid athletics and so on, but it wasn’t Aside from my backhand weakness, I profession. With all this in mind, I until my medical-school years that I know the game very well. have no complaints. fell in love with tennis. I was intro- But even before I came across ten- However, we are all born with other duced to the sport in the early 1980s nis, as a 15-year-old from (a passions that we do not necessarily when I traveled for the rst time to former British colony), I began discov-

42 ASBMB TODAY MARCH 2017 Diamandis with Canadian tennis player Eugenie Bouchard ering in 1967 the Beatles, the Rolling tronic library now has more than Consequently, I would prefer a com- Stones and the other rock groups by 300,000 songs, split equally between posite of professions: From Monday listening to English radio stations. I Greek and English. Everywhere I go, to Friday I would operate my research religiously followed “Top 20,” a radio I carry my iPod as well as my iPhone, laboratory, aiming toward discover- show based in England, and meticu- which are loaded with music. When ing and publishing new knowledge lously took notes on the ranking of I nd ve or more minutes of spare and mentoring young students. On the songs and the bands. Despite time, I listen to music. During my Saturday, I would work for a television having no musical background in my wife’s shopping expeditions, I pass the station as a commentator for sporting family, I was obsessed with listening time with music, secretly wishing she events, particularly tennis. On Sunday, to music with my transistor radio on would do more shopping so I could I would host my own radio show, every occasion and became procient extend my enjoyment! While I can during which I would play the music I at knowing every single song of that spend 70 minutes daily on a treadmill like and tell the stories behind the hits! era. I was the human Shazam of my exercising with music, I am not able to Realistic? Probably not. Crazy? time (Shazam is the mobile app that do a single minute of exercise without Denitely yes. From here, I suppose identies music). By 1970, my heroes music. In short, music is an absolute my only hope for a second profession included Neil Diamond, Neil Young, necessity in my life. Unfortunately, (and proclaim, like Britney Spears, Led Zeppelin, AC/DC and e Who, I do not seem to have any talent in “Oops! … I Did It Again”) is to nd among many others. When I was serv- creating new music. My talent is only the “Stairway to Heaven.” ing in the Cyprus Army as a soldier, I in listening. was punished and put in prison many I still am highly fascinated with the times for breaking the rules and listen- discovery process and the mentoring Eleftherios P. Diamandis (Elefthe- rios.Diamandis@sinaihealthsys- ing to music while on guard service. of young individuals, such that I could tem.ca) is professor and head of My passion for music grew not imagine that I would leave this the division of clinical biochemis- immensely over the years. My elec- activity if presented a second chance. try in the department of laboratory medicine and pathobiology at the , biochemist-in-chief at University Health REFERENCES Network, and division head of clinical biochemis- try at Mount Sinai Hospital, Toronto. 1. Diamandis, E.P., Clin. Chem. 55,1253 – 1254 (2009).

MARCH 2017 ASBMB TODAY 43 OPEN CHANNELS Make or break By Vivian Tang

With lots of data in hand, I yearn for them to make sense. Count on no one to understand, Publish or perish — that’s common sense.

One postdoc appointment after another, Craving for clarity in my academic prospect And the bandwidth to go further. If only I can turn back the clock, in retrospect.

I would perhaps take the industrial route. Far less pressure to publish, My hard work would still bear fruit, Even a career I’d relish.

A career in a core facility? Academics get the thrills and spills, But I enjoy greater job stability, And they may owe their success to my skills.

Might also consider science writing, Instead of being too much an idealist. Could that have been my calling? Told of my air for engaging nonscientists.

A passion to shape the society through research, To advocate for improved scientic eciency As a liaison ocer in research. Another possible career path — science policy.

My love for science ction — It’s often quite easy to spin a tale, And it’s become an addiction. Could have been led by that without fail? Need extra rigor To keep my passion burning. Of course I’m eager To do the soul-searching. Vivian Tang (victoriousvivian@ Is the bigger picture still in sight? hotmail.com) is a graduate Is it not a failure but a test of character? student at the school of pathology Perhaps the nal battle is worth a ght. and laboratory medicine at the University of Western Australia. Which means my best simply has to get better.

44 ASBMB TODAY MARCH 2017 MARCH 2017 ASBMB TODAY c7