Vol. 13 / No. 7 / August 2014

The member magazine of The American Society For Biochemistry And Molecular Biology CONTENTS

NEWS FEATURES PERSPECTIVES

2 21 32 PRESIDENT’S MESSAGE ‘ON THE SAME WAVELENGTH’ ESSAY 2015 CALLS FOR Down but not out 32 e amazing green uorescent protein 30 35 Uncovering the unexpected 4 A TALE OF FRIENDLY NEWS FRUIT FLIES IN A JAM 36 SUBMISSIONS ASBMB annual award winners Author of new children’s book hopes cute EDUCATION and curious cast of characters will ignite Curricular revision: embracing the journey appreciation for model organisms HOBBIES 5 NEWS FROM THE HILL 5 39 We know that a life in science can be grueling. We also know that some of you Water, water everywhere – MINORITY AFFAIRS have very interesting or unusual ways of blowing o steam or nding your Zen. and not a drop to drink Q&A with Pumtiwitt McCarthy We would like to feature your essays, poems, artwork or multimedia reecting on scientists’ pastimes. We welcome all creative interpretations of the theme. You could send us a photo of you shooting hoops or jumping out of an airplane. You could 6 40 MEMBER UPDATE send us a video of you jamming with your band. You could send us a poem about a PROFESSIONAL DEVELOPMENT childhood hobby or otherwise abandoned escapes. You could write about a hobby 40 Looking beyond the lab enjoyed by someone else — perhaps a gure in science history or one of your men- 8 42 Moving into administration: tors. And you could send us a rant about how you don’t have time for such frivolity. JOURNAL NEWS Is it really that dicult? 17 44 GENERATIONS NEWS OUTREACH is collection of essays, poems and artwork will explore generations in a very Report highlights nonacademic careers 30 e CAISE for informal science education loosely dened way. You might have come from a family of scientists. You might of STEM Ph.D. holders have insights about parenting while doing science. You might have something to say 47 about generations of cell lines or scientic lines of inquiry. You might have a story 20 OPEN LETTERS to tell about a line of researchers mentored by one scientist. Interpret the theme as NIH UPDATE An open letter to press ocers who won’t you will. It is not a boundary but rather a springboard for the making of meaning. NIH launches a public website promote unembargoed research papers for bioscienti c 3-D printing 47 DEADLINES FOR HOBBIES AND GENERATIONS: Dec. 31, 2014. 2

FORMAT: We’ll print some; others, we will post online. Some might appear both in print and online.

SUBMISSIONS: Email (to [email protected]) your manuscripts as Word documents, static images as JPEG or TIFF les (the higher the resolution the better), audio as mp3 or 21 4 mp4 les, and videos in something like QuickTime, Vimeo or YouTube. Please indicate to Science writer Rajendrani which series you are submitting in your email subject line. Mukhopadhyay writes about Jennifer Doudna’s work on CRISPR and her partnership with her lab manager, Kaihong Zhou. Image courtesy of Cailey Cotner/University of California, Berkeley.

AUGUST 2014 ASBMB TODAY 1 PRESIDENT’S MESSAGE

will tell if the investment will pay o . data science. Here is the idea on big science. e point I THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY Once we gather enough of it, really seek to make FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY Down but not out smart people will be able to extract in this inau- By Steven McKnight all of the diamonds of biology. gural essay OFFICERS COUNCIL MEMBERS Magically, for example, they will is the simple Steven McKnight Natalie Ahn be able to use big data to predict prediction President Squire J. Booker correctly that cells have an enzyme that, as we Karen G. Fleming y colleague George DeMar- biochemistry. Jeremy M. Berg that senses intracellular DNA and peer into the Past President Gregory Gatto Jr. tino at the University of ere are two wonderful things Daniel Leahy Karen Allen then triggers the production of cyclic looking glass Anjana Rao Texas Southwestern Medical about the gathering of huge data sets. Secretary M GAMP, which then activates the of the future, Jared Rutter Center at Dallas told me a humorous First, it is can’t-fail science. If I tell a Toni Antalis STING enzyme to mount an innate Chen- and Brenda Schulman story that indicates the devolved state trainee to immunopurify fragmented Treasurer Michael Summers immune response. When this hap- Cech-like of our beloved eld of biochemistry. chromatin with an antibody to one pens, we won’t need the biochemical discover- EX-OFFICIO MEMBERS ASBMB TODAY EDITORIAL George uses biochemical approaches of our transcription factors and then skills of James Chen, who painstak- ies abound. COURTESY OF WIKIMEDIA COMMONS USER NLAN86 Dorothy Beckett ADVISORY BOARD to study the proteasome, including have our genomics core sequence Mary Roberts ingly discovered the aforementioned Not being A claw crane game in Trouville, France, promises plush unicorns. Charles Brenner standard methods of protein purica- the precipitated DNA, the experi- Co-chairs, 2015 Annual Chair pathway. a gambler, I Meeting Program tion. While interviewing a prospec- ment will work every time. What a Michael Bradley Had we had access to big data will not short the stock of big data of fashion may fade into extinction. Committee tive postdoctoral candidate, George deal it is to carry out fail-safe experi- Floyd “Ski” Chilton science 30 years ago, we would not in anticipation of the bursting of its I trust that readers will see where my Peter J. Kennelly Cristy Gelling explained how he routinely puries ments! Second, the top-tier journals Chair, Education and Peter J. Kennelly have needed Tom Cech’s chemical bubble. On the other hand, given money is: We biochemists are down the proteasome, starting with bovine eat this sort of research up as if it Professional Development Rajini Rao and biochemical acumen to discover that the market cap of mechanistic but not out. Committee blood obtained from a local slaugh- were $1,000-per-ounce caviar. ose Yolanda Sanchez catalytic RNA. Geez, would life have biochemistry may be at an all-time Daniel Raben Shiladitya Sengupta terhouse. As the interview progressed, of us who have stuck with dicult Chair, Meetings Committee Carol Shoulders been simpler! e magic claw of big low, I could not be more bullish on the applicant lauded George on his and uncertain biochemical research Steven McKnight (steven. data science could have seen all of the our stock. Takita Felder Sumter ability to study the puried macro- are viewed as village idiots — how [email protected]) Chair, Minority Aairs ASBMB TODAY discoveries of signicance and simply Time will tell whether big data is president of the American Committee molecular machine and stumbled into could we be so stupid not to see the Angela Hopp plucked them out of the pile of mas- science is just a Ponzi scheme or will Society for Biochemistry and Editor, [email protected] omas Baldwin the telling question of the interview: light? sive data sets. instead dazzle us with magnicent Molecular Biology and chairman Chair, Outreach Committee Rajendrani Mukhopadhyay “at’s really cool, but how did you My friend Deepak Nijhawan OK, enough foolishness. ere is discoveries. If it does, the reduction- of the biochemistry department at the University Bob Matthews Sr. Science Writer, get the His tag into the cow?” o ered a visual correlative of big data of Texas-Southwestern Medical Center at Dallas. Chair, Public Aairs [email protected] a place for everything, including big ist, mechanistic approaches now out Advisory Committee Marnay Harris It is the unfortunate case that few science. When we take our kids to Kathleen Collins Designer, [email protected] of our trainees have any clue about a venue o ering a variety of arcade Chair, Publications Andrew Harmon ammonium sulfate cuts, di erential games, they gravitate to the game that Committee Science and Technology Publishing Manager, centrifugation or column chromatog- consists of a claw that can be moved Martha J. Fedor [email protected] Editor-in-chief, JBC raphy. Young scientists instead think in X, Y and Z dimensions by a joy- COUNCIL Ciarán Finn anity-precipitation of a tagged, stick. Below the claw lies a carpet of NEW TO THE ASBMB GOVERNANCE: Herbert Tabor Web Assistant, c [email protected] Karen Fleming, Johns Hopkins University Co-editor, JBC overexpressed protein constitutes stu ed toys, perhaps including frogs, Karen Schools Colson Jared Rutter, University of Utah A. L. Burlingame Director of Publications, “biochemistry.” bunnies, crocodiles and bears. It is so Michael Summers, University of Maryland, Baltimore County Editor, MCP [email protected] Few would dispute that our eld is incredibly easy! Edward A. Dennis Barbara Gordon out of fashion. What is the in-vogue Our kids put their quarters in, Joseph L. Witztum Executive Director, NOMINATING COMMITTEE Co-editors, JLR [email protected] science that obscures biochemistry maneuver the claw and drop it into Dana Carroll, University of Utah School of Medicine like a full eclipse of the sun? Topping place to retrieve the exact stu ed Benjamin Cravatt, e Scripps Research Institute the list is the big data science evolving animals of their desires. Over time, from genomics. they learn the hard way that this PUBLICATIONS COMMITTEE For information on advertising, contact Fox Associates Inc. e ever-expanding iterations of never works. Indeed, I have never Jeanne Hardy, University of Massachusetts Amherst at 800-440-0231 or [email protected]. -omics research o er limitless access seen it work a single time in my Amnon Kohen, University of Iowa to data. e challenge of gathering entire life. What a racket — an fresh data used to be dicult; now innite number of quarters for noth- PUBLIC AFFAIRS ADVISORY COMMITTEE it’s a piece of cake. I venture to guess ing. Even if the claw wins once in a Stephen Buxser, Nerac www.asbmb.org/asbmbtoday that the amount of data gathered and thousand attempts, the reward is a Sonia Flores, University of Colorado Anschutz Medical Campus PRINT ISSN 2372-0409 published by the ENCODE consor- stu ed animal that may have cost less Matt Gentry, University of Kentucky Articles published in ASBMB Today reect solely the tium last year might, in aggregate, to produce than the 25-cent price of Sharona Gordon, University of Washington authors’ views and not the ocial positions of the American Society for Biochemistry and Molecular constitute a larger amount of data admission! Just as our kids mindlessly Jack Kaplan, University of Illinois at Chicago Biology or the institutions with which the authors are than what has been accumulated feed the claw, the National Institutes aliated. Endorsement by ASBMB Today or ASBMB Mike Schaller, West Virginia University of products or services mentioned is not implied. in the entire history of the eld of of Health feeds big data science. Time

2 ASBMB TODAY AUGUST 2014 AUGUST 2014 ASBMB TODAY 3 NEWS NEWS FROM THE HILL Water, water everywhere — and not a drop to drink By Benjamin Corb

n years past, there has been a intended proposals with results. ing research not just for America’s healthy line of strong voices sup- e 535 members of Congress status in the world but for the health I porting the research community, represent Americans from all walks and well-being of their own family and those backers have followed up of life, and I spend much of my members and neighbors. Scientists PLENARY LECTURER ASBMB AWARD FOR EXEMPLARY WILLIAM C. ROSE AWARD their talk with action by increasing professional life talking with these can no longer be a silent constitu- C. David Allis, e Rockefeller University CONTRIBUTIONS TO EDUCATION Kathleen Matthews, Rice University funding at agencies like the National lawmakers and their sta members ency without the time or interest to J. Ellis Bell, University of Richmond Institutes of Health. about the importance of supporting get involved. Furthermore, science PLENARY LECTURER WALTER A. SHAW YOUNG INVESTIGATOR Take, for instance, Newt Gingrich, and funding biomedical research. e proponents need to be savvier and Bonnie L. Bassler, Princeton University ASBMB YOUNG INVESTIGATOR AWARD AWARD IN LIPID RESEARCH the former speaker of the U.S. House more time I spend talking with them, hold elected ocials accountable Erica Ollmann Saphire, Britta Brügger, Heidelberg University when their words and actions don’t PLENARY LECTURER e Scripps Research Institute of Representatives, and U.S. Rep. the more I become convinced that match. If current trends continue, Ian A. Wilson, HERBERT TABOR RESEARCH AWARD John Porter, both Republicans who biomedical research is just not a prior- many scientists will have more time e Scripps Research Institute AVANTI AWARD IN LIPIDS Joan A. Steitz, Howard Hughes Medical played essential roles in orchestrat- ity for them. Certainly, you’d be hard- Karen Reue, David Geen School of Institute, Yale University ing the doubling of the NIH budget pressed to nd a member of Congress on their hands than they know what PLENARY LECTURER Medicine, University of California, Los Angeles in the early 2000s. And then there who is against biomedical research or to do with. ASBMB–MERCK AWARD EARL AND THRESSA STADTMAN was U.S. Sen. Arlen Specter, the against increasing the NIH budget, If you want to turn the tide, the Zhijian James Chen, University of Texas MILDRED COHN AWARD DISTINGUISHED SCIENTIST AWARD Republican-turned-Democrat who but it’s a lot harder to nd someone American Society for Biochemistry Southwestern Medical Center at Dallas IN BIOLOGICAL CHEMISTRY Jack E. Dixon, single-handedly fought for $10 billion actually willing to ght for either. and Molecular Biology can help by Judith P. Klinman, University of California, San Diego in federal stimulus funds for the NIH And the reason is simple. ey’re not informing you of what’s happening in PLENARY LECTURER University of California, Berkeley in 2009. ese members of Congress hearing from their constituents that Washington or setting up a meeting FRITZ LIPMANN LECTURESHIP BERT AND NATALIE VALLEE AWARD valued federal investment in the research and research funding are for you with your elected ocials as Rachel Klevit, University of Washington DELANO AWARD IN BIOMEDICAL SCIENCE research enterprise and provided tan- important issues worth ghting for. part of the ASBMB 50-State Chal- FOR COMPUTATIONAL BIOSCIENCES David Eisenberg, University of gible results that shaped the research ese observations underscore the lenge. Isn’t it time we all move beyond Vijay Pande, Stanford University California, Los Angeles, Department of Energy community into what it is today. need for scientists to build stron- lip service? More recently, however, the bench ger relationships with their elected RUTH KIRSCHSTEIN DIVERSITY ALICE AND C.C. WANG AWARD of real champions for research has ocials. Why am I putting the onus How to participate IN SCIENCE AWARD IN MOLECULAR PARASITOLOGY grown rather thin. on scientists? Because you are the Do you want to meet with your JoAnn Trejo, Alan F. Cowman, U.S. Rep. Rosa DeLauro, an out- constituents! You have the ears of your member of Congress and his or University of California, San Diego University of Melbourne spoken Democrat from Connecticut elected representatives. Whether your her sta during the summer recess and a cancer survivor, is among the representative is giving speeches about (Aug. 1–Sep. 5)? Register now for loudest and strongest NIH support- immigration reform, scal responsibil- the ASBMB ers on Capitol Hill. Sadly, DeLauro ity or anything else, it’s because that 50-State Challenge. works in the House of Representa- person’s constituents have conveyed More infor- tives, which has reached a point of the message that those topics are mation at near uselessness, as partisan politics important. And as much as I’d like www.asbmb. and unwillingness to compromise rule for members of Congress to follow org/50state the day. Republican U.S. Sen. Jerry through on their talk by funding Moran from Kansas also has shown research, it’s the scientist-constituents sincere interest in supporting funding who have to pressure elected represen- Benjamin Corb (bcorb@asbmb. for the NIH and even has proposed tatives into putting their money where org) is director of public affairs funding increases (heresy to many in their mouths are. at ASBMB. his party) but has yet to reach a posi- Scientists must help lawmakers tion of authority to follow his well- understand the importance of fund-

4 ASBMB TODAY AUGUST 2014 AUGUST 2014 ASBMB TODAY 5 MEMBER UPDATE

the Perelman School of Medicine’s signicant contributions to the a ects diseases, including cancer, members Robin and Jack Ross, was genetics department at the University national, economic and energy autoimmune disorders and other given on June 9 at the New York of Pennsylvania. He has been at Penn security of the United States, illnesses. Academy of Sciences in Manhattan. for 20 years and holds multiple strengthening U.S. leadership in e award is given to an active leadership roles there. In addition to discovery and innovation. Each Lanier made VP for investigator who has produced heading the Division of Translational recipient will receive a medal and a innovative, paradigm-shifting Medicine and Human Genetics, Rader $20,000 honorarium at a ceremony in research at Wayne State research that is worthy of signicant serves as associate director of the Washington, D.C., later this year. Stephen M. Lanier and broad attention in the eld of Institute for Translational Medicine Image courtesy of Peg Skorpinski. has been molecular medicine. O’Shea has been and erapeutics and co-directs the appointed Wayne a physician and immunologist at the new Penn Medicine BioBank. Rader Neet appointed to FASEB State University’s NIH for 33 years and has made has had a long interest in Mendelian vice president for fundamental discoveries related to the disorders of lipoprotein metabolism finance committee research. Lanier signaling of cytokines. His research LANIER and has a strong translational interest Kenneth Neet had been the has focused on the molecular cause of in development of novel therapies for recently was associate provost for research and a primary immunodeciencies, these disorders. Along with numerous appointed to the professor of cell and molecular inherited conditions in which the awards as a physician-scientist, he has nance committee pharmacology and experimental immune function is impaired and the received recognition for his outstand- of the Federation therapeutics at the Medical University genetic basis of autoinammatory ing teaching. of American disorders. O’Shea has received NEET of South Carolina. Lanier has served Societies for on multiple review panels for the numerous awards and is a fellow of Berkeley Lab’s Arkin wins Experimental Biology. Neet is a National Institutes of Health and has the American Association for the George Carman of Rutgers University, left, in June gave a Journal of Lipid Research-sponsored lecture at a professor and the associate dean of developed a number of collaborative Advancement of Science. research conference held by the Federation of American Societies for Experimental Biology. The conference Lawrence Award research at the Rosalind Franklin initiatives across departments and focused on phospholipid cell signaling and metabolism in inflammation and cancer. Carman’s lecture was Biologist Adam titled “Phosphatidate phosphatase in lipid signaling.” JLR co-Editor-in-Chief Edward Dennis, right, presented University of Medicine and Science in colleges. e president of Wayne State, IN MEMORIAM: Arkin, director of a plaque to Carman in recognition of the prestigious lectureship. Illinois. Neet, who studies neurobiol- M. Roy Wilson, stated, “We are Ivana Weygan–Durasevic Berkeley Lab’s ogy, has served on the editorial boards delighted to welcome Dr. Lanier to mitochondrial bioenergetics and has Ivana Weygan– Plant biologists Siedow Physical Biosci- of many science journals and as a Wayne State. He brings a wealth of been a strong advocate for plant biol- Durasevic passed ences Division, is member of study sections for the talent and experience to this position, and Guilfoyle recognized ogy research. away April 7 in one of six National Institutes of Health and the including extensive experience in omas J. Guilfoyle of the Uni- ARKIN Zagreb, Republic recipients of the National Science Foundation. In addi- technology transfer.” Lanier expressed versity of Missouri won the Lawrence 2013 Ernest Orlando Lawrence of Croatia. Born tion, he served many years as an his eagerness to join the institution, Bogorad Award for Excellence in Award presented by U.S. Energy in 1952, Weygan– associate editor for the ASBMB’s saying, “Wayne State University has a WEYGAN-DURASEVIC Plant Biology Research in recognition Secretary Ernest Moniz. He is Durasevic studied Journal of Biological Chemistry. number of outstanding, internation- of his many contributions to plant recognized as a leading authority on chemistry and molecular biology at ally recognized research programs and biology. His work has illuminated new the evolutionary design principles of the University of Zagreb. She joined SIEDOW GUILFOYLE Varshavsky wins Albany is playing a critical role in the develop- paths of research in plant hormone cellular networks and populations and the university as a faculty member in ment of the local and regional e American Society of Plant signaling and has propelled discover- their application to systems and Medical Center prize 1975 and was an internationally community.” Biologists named two members of the ies in plant transcriptional regulation, synthetic biology. e thrust of Alexander recognized expert in the eld of American Society for Biochemistry viral replication and auxin biology. In Arkin’s research has focused on Varshavsky is the tRNA and aminoacyl-tRNA syn- and Molecular Biology as recipients of addition, his dedication and generos- developing physical theory, computa- 2014 recipient of O’Shea to receive thases, molecules involved in protein its 2014 awards, honoring excellence ity have inspired many plant biologists tional tools and experimental the Albany Ross Prize in Molecular biosynthesis. During her career, she in research, education, outreach and and students. approaches for understanding the Medical Center authored more than 70 papers and service. cellular processes that are critical to Prize in Medicine. Medicine four book chapters, and in 2005 she VARSHAVSKY James N. Siedow of Duke Uni- Rader named chair of life. e goal is to provide a frame- e $500,000 John J. O’Shea, received the highly prestigious versity won the Charles Reid Barnes University of Pennsylvania work that will facilitate the design and award, given annually since 2001, is scientic director Croatian National Science Award. Life Membership Award. e Barnes engineering of new functions and one of the largest prizes in medicine at the National Her excellent scientic and teaching award is the ASPB’s oldest award and medical school behaviors in cells through synthetic and science in the United States. Institute of Arthri- career earned her election into the was established in 1925 to honor Daniel J. Rader, a and systems biology. e Department Varshavsky is a professor of cell tis and Musculo- Croatian Academy of Sciences and lifelong service in plant biology. Sie- leader in human skeletal and Skin Arts in 2012. Weygan–Durasevic of Energy’s E.O. Lawrence Awards biology at the California Institute of O’SHEA dow will be recognized and honored genetics of were established in 1959 to honor Technology. e focus of his research Diseases, has been is remembered by colleagues as a for both his stellar research in plant lipoprotein biology Ernest Lawrence, the Nobel Prize- is the ubiquitin system. He received named the 2014 recipient of the Ross dedicated teacher, supportive mentor, biochemistry and his service to the and cardiovascular winning inventor of the particle this award for his landmark discover- Prize in Molecular Medicine. e and collaborator for renowned and plant biology community. Siedow has disease, was named accelerator known as the cyclotron. ies that have transformed our award, which includes a $50,000 internationally recognized scientists. RADER made a large impact in the eld of the new chair of Moniz said that the recipients made understanding of how cell behavior prize from Feinstein Institute board Written by Nicole Parker

6 ASBMB TODAY AUGUST 2014 AUGUST 2014 ASBMB TODAY 7 JOURNAL NEWS ‘Nature’s escape artists’ The intricacies of the calcium ion-binding motif ematic series explores the various functions and applications of intein-mediated protein splicing in the βγ-crystallin domain By Jenna Hendershot By Emily Tsai Post-translational protein splicing networks, the authors conclude, may occurs when intervening intein poly- play a larger role in determining intein What do a bacterial spore coat and a e partnering Greek key motifs and the extent of gain in stability var- peptides excise themselves from larger activity than previously thought, human eye lens have in common? For share one β-strand (out of four). On ies from domain to domain. precursor proteins and ligate their because mutations distal from the one, the presence of βγ-crystallins. top of the domain lie two (N/D)- “e Ca2+-binding motif of surrounding polypeptides, known as active site can modulate intein activity. e βγ-crystallins are a superfamily (N/D)-(X)-(X)-(T/S)-(S) sequence βγ-crystallins is spectacular not only exteins. is is accomplished by a mul- In the nal minireview, David of Ca2+-binding proteins, grouped stretches that connect the third and in its composition of a nonlinear tistep enzymatic reaction mediated by W. Wood and Julio A. Camarero on the basis of their characteristic fourth strands from their respective sequence of amino acids but also in the intein. Sometimes called “nature’s share advances in the applications Greek key topology, that share a Greek key motifs. Each calcium ion that it acts as a thread to connect escape artists,” inteins are proteins that of inteins. Early engineered inteins calcium-binding motif. Because the is coordinated by residues from both an extensively diverse and chrono- have been found in microorganisms were used in protein purication, but Ca2+-binding motif is evolutionarily sequence stretches and the β-hairpin logically vast array of proteins,” says from all domains of life. now optimized trans-splicing and conserved, learning more about it in loop between the rst and second Sharma. “Evolution of this motif Even though the rst intein trans-cleaving inteins have enabled bacteria could improve our under- β-strand. displays the footprint of adaptations βγ sequence was published 25 years ago, a wide variety of applications in standing of it in other domains of In a βγ-crystallin domain, the that the -crystallin superfamily has life. In the Journal of Biological Ca2+-binding site generally has a coor- undergone.” details of the splicing mechanism protein labeling, metabolic engi- 2+ are just beginning to be elucidated. neering, biomaterials construction, Chemistry, biophysicist Yogendra dination number of seven, including While the Ca coordination pat- Inteins have fascinated scientists for intein-based biosensors, gene delivery Sharma and his group at the Centre four protein ligands and three water tern has been well studied, very little is known regarding the functions of years, and they have been shown to and protein cyclization. ese new for Cellular and Molecular Biol- molecules, and forms a pentagonal In the second minireview, Ken- many βγ-crystallins. Current data have a wide variety of applications techniques allow specic control over ogy in India review the intricacies bipyramidal geometry. Ca2+-coordina- neth V. Mills, Margaret A. Johnson suggest that many of these Ca2+- in protein engineering and drug biological functions of proteins in of the Ca2+-binding motif in the tion is mediated via second, third and and Francine B. Perler focus on the binding βγ-crystallins are relevant discovery. A new thematic miniseries living cells, plants and whole animals. βγ-crystallin domain. e authors fth residues of the (N/D)-(N/D)- wide variety of splicing mechanisms. with stress, virulency or adhesion. on intein-mediated protein splicing Future applications will build on these cover the architecture of the Ca2+- (X)-(X)-(T/S)-(S) stretch, along with Inteins have evolved to regulate tightly As more members of this group are appeared in a recent issue of e techniques and promise to reveal new 2+ coordination, one residue of the β-hairpin, while the steps of splicing; however, inteins binding motif and Ca being identied, further research is Journal of Biological Chemistry. classes of therapeutic proteins. paying special attention to Ca2+ the rst residue of the (N/D)-(N/D)- don’t use a universal mechanism. is coor- needed to explore the Ca2+-dependent In the rst minireview, Olga e four minireviews in this review discusses the general strategies dination by the signature sequence (X)-(X)-(T/S)-(S) stretch may play a functions of βγ-crystallins. Novikova, Natalya Topilina and for catalysis and the roles of various series help to broaden our thinking residues of the Ca2+-binding site. role in stabilizing the pocket through Marlene Belfort discuss the overall amino acids during splicing. While about protein splicing. In an edito- In the crystal structure of a typi- hydrogen bonding. Meanwhile, Emily Tsai ([email protected]) recently completed postdoctoral function of inteins and the sporadic the basic steps in protein splicing have rial commentary, Perler and Norma cal βγ-crystallin, such as Clostrillin the fourth residue of the stretch is research studies at the Johns Hop- distribution of inteins among closely been known since the 1990s, how M. Allewell conclude that signicant from the bacterium Clostridium involved in forming a hydrophobic kins University School of Medicine related species. Overall, there is a the reactions are coordinated is still progress has been made to bet- beijerinckii, two Greek key motifs core. Ca2+ binding is important for department of radiation oncology bias for inteins to insert into proteins unknown. Detailed kinetic and struc- ter understand intein mechanisms; together form the Ca2+-binding sites. stabilizing the βγ-crystallin domain, and molecular radiation sciences. involved in DNA metabolism, such as tural studies are needed of multiple however, there are still many unan- polymerases, helicases and topoisom- inteins to determine whether catalytic swered questions. While evolutionary erases. In addition, inteins normally strategies are universal or specic to a biologists question whether inteins are located at protein active sites or in subset of inteins. are selsh elements and biochemists key ligand-binding surfaces. While the Ertan Eryilmaz, Neel Shah, Tom seek to understand how inteins work, Unfolded protein response signaling rationale for intein localization is still Muir and David Cowburn explore in intein-mediated protein splicing cre- a matter of debate, the authors men- the third minireview the structural fea- ates opportunities in many scientic and metabolic diseases tion the importance of intein reten- tures of inteins and the variability in areas. e numerous intein applica- tion. Improper removal of an intein splicing mechanisms. While all inteins tions have huge potential for modi- By Teodora Donisan within a conserved protein motif share the same fold and have highly fying, synthesizing and controlling would be deleterious and therefore conserved sequence motifs, inteins protein function in the future. e ever-rising worldwide incidence of studies for two decades already, and Umut Ozcan at Boston Chil- ensures retention of an active intein have surprisingly di erent splicing of metabolic diseases, such as obesity appears to be intimately involved, dren’s Hospital detail the correlation eciencies. is review describes Jenna Hendershot (hendeje@ for viability of the host. Understand- umich.edu) earned a B.S. in cel- and type 2 diabetes, has made them making it a good candidate for phar- between ER stress and metabolic ing the evolution and distribution of the structural basis of protein splic- lular and molecular biology from an important target for researchers. macologic interventions. changes, highlighting some plausible inteins will shed light on the possibil- ing, intein dependence on exteins for Grand Valley State University and e therapeutic options available so In a minireview recently pub- therapeutic solutions. ity that inteins function as unique protein splicing and distal mutations is completing her Ph.D. in biologi- far are rather scarce. Endoplasmic lished in the Journal of Biological cal chemistry at the University of Michigan. regulatory elements. that a ect protein splicing. Allosteric reticulum, or ER, stress, the focus Chemistry, researchers Jaemin Lee CONTINUED ON PAGE 10

8 ASBMB TODAY AUGUST 2014 AUGUST 2014 ASBMB TODAY 9 CONTINUED FROM PAGE 9 minireview published in the Journal dehydrogenase, dihydrolipoamide e activity of human PDC is tightly e ER is an essential organelle of Biological Chemistry recently. acetyltransferase and dihydroli- regulated by tissue-specic kinases for protein biosynthesis. It processes In this review, Mulchand S. Patel poamide dehydrogenase, which work and phosphatases, which respond newly synthesized proteins, modi- and colleagues have compiled the in tandem to convert pyruvate in to to di erent nutritional and disease latest developments in PDC research, acetyl-CoA, CO and NADH (H+). states. For example, some cancer fying and folding them according 2 cells have activated levels of the to rigorous quality standards. is compared PDC structural and regula- Acetyl-CoA is then used as a substrate kinase1, resulting in inhibition of process is dynamically adjusted tory mechanisms in bacteria and in in the Krebs cycle to generate ATP or PDC, which is not favorable for depending on the physiological status humans, and considered their impli- used for biosynthetic processes, such normal cells but is suitable for cancer- of cells. ER stress appears when the cations on human health. Patel, a as lipid formation. e unique inter- cell survival and growth. By studying workload exceeds the folding pos- distinguished professor and associate actions among these components in structural and compositional aspects sibilities of the ER, activating a com- dean at the State University of New the complex ensure eciency as well of the human PDC and its regula- pensatory system called the unfolded York at Bu alo, and Frank Jordan, as regulation of the aforementioned tion, one can exploit mechanistic protein response, or UPR. e UPR a professor at Rutgers University, metabolic process. e downside of di erences for therapeutic advantages tries to increase the resources that Newark, have collaborated for several the human complex is that even a to combat cancer and other human the ER needs to fold more proteins years to understand the evolutionary minor change in the complex can diseases. and to reduce the protein load in changes leading to the functioning of have a profound impact on health the ER, but if the ER fails to do so these multienzyme complexes, have conditions ranging from neurodegen- for prolonged periods of time, UPR used novel methods to identify dif- erative disorders to obesity, type-2 Alok Upadhyay (alok7930@gmail. ferent steps in the catalytic reactions, diabetes, and some types of cancer. com) is a postdoctoral associate signaling initiates cell death. at Fox Chase Cancer Center. His e UPR has three branches medi- and have elucidated high-resolution In contrast with E. coli PDC, major research area is Notch ated by three ER transmembrane UPR signaling and its cross-talk mediated by IRE1, PERK and ATF6 structures of several PDC component mammalian PDCs have an additional signaling regulation during cell proteins: IRE1, or inositol-requiring proteins. structural component (a binding fate decisions and neural crest stem cell develop- ATPase, or SERCA, dysfunction; tivity and glucose homeostasis, and PDC is composed of three distinct protein) and specic kinases and ment. Follow him on Twitter at www.twitter.com/ protein-1; PERK, or protein kinase alok7667. RNA-like ER-kinase; and ATF6, cholestasis and high levels of circulat- reduce hepatic lipogenesis. catalytic enzymes, namely pyruvate phosphatases for stringent regulation. or activating transcription factor-6 ing homocysteine; and by fatty acids, Also, attempts have been made (see gure). In their minireview, Lee oxidized lipids, cholesterol and hyper- to modulate specic components of and Ozcan summarize the current homocysteinemia. While the causes the UPR as potential treatments for understanding of how IRE1, PERK of ER stress vary, all mechanisms that metabolic disorders and multiple and ATF6 pathways work and how induce ER stress involve IRE1, PERK myeloma (IRE1 modulators) and for The many levels of glycolytic flux regulation they interact with other signaling and ATF6. inhibiting tumor growth and neu- networks. e minireview notes that not rodegeneration (PERK inhibitors). By Kathleen McCann ER stress can be induced in major only have various studies elucidated Lee and Ozcan emphasize the need for more pharmacologic endeavors metabolic disorders like leptin and the mechanisms responsible for some β focused on UPR components. Glycolysis is a fundamental metabolic and pancreatic cells, also express insulin resistance, nonalcoholic fatty of the pathophysiological changes, pathway that is critical for the pro- glucokinase, which has a much lower but they’ve also shown that chemical liver disease, and atherosclerosis. ER Teodora Donisan (teodora. duction of energy. Glycolytic ux, or anity for glucose. e unique stress is caused in these conditions chaperones reducing ER stress (e.g., [email protected]) is a medical the rate at which molecules proceed kinetic properties of glucokinase by increased levels of reactive oxygen 4-phenylbutyric acid and taurour- student at Carol Davila University through the glycolytic pathway, is allow it to act as a glucose sensor and in Bucharest, Romania. species and ER calcium depletion by sodeoxycholic acid) restore leptin tightly regulated in response to the translate changes in blood-glucose sarco/endoplasmic reticulum calcium responsivity, improve insulin sensi- cellular environment. In a recent levels into changes in glycolytic ux. minireview in the Journal of Bio- It long has been thought that glu- logical Chemistry, Sigurd Lenzen cokinase function is weakly regulated. of the Hannover Medical School However, in the past few decades, in Germany describes the complex a number of studies have begun to Pyruvate dehydrogenase complex regulatory mechanisms underlying demonstrate that glucokinase activity From energy generation to novel drug target glycolytic ux. is not only regulated, but it is regu- Glycolytic ux is regulated during lated di erently in di erent cell types. By Alok Upadhyay the initial steps of glycolysis, includ- For example, in the liver, glucokinase ing glucose uptake and phosphoryla- is inhibited by GRP, a nuclear protein The regulatory unit of the glycolytic pathway com- posed of the fructose steps at the interface between Energy generation in prokaryotic pathway, generating pyruvate and amounts of ATP required for cellular tion. Phosphorylation of glucose is that selectively binds and inactivates the initial step of glucose trapping in the cell through and eukaryotic organisms is a highly small amounts of ATP. To harness functions. e key enzyme complex carried out by hexokinases. While all glucokinase during starvation. Glu- phosphorylation and the conditioning of the glucose molecule for catabolism. ecient, multistep and tightly regu- the full energy content of glucose, bridging these two processes is known cells express at least one hexokinase cokinase also is inhibited in β cells, lated process. Normally, glucose is pyruvate undergoes further oxidation as the pyruvate dehydrogenase com- with extremely high anity for glu- although that is done by ubiquitin CONTINUED ON PAGE 12 metabolized initially via the glycolytic in the Krebs cycle, generating large plex, or PDC, and is the subject of a cose, select cell types, including liver and ubiquitin-binding proteins, as

10 ASBMB TODAY AUGUST 2014 AUGUST 2014 ASBMB TODAY 11 CONTINUED FROM PAGE 11 are formed inuence glycolytic ux more complex than initially thought. paper’s authors point to two pos- might ordinarily get broken down in be recommended to reduce cardiovas- GRP is not expressed in those cells. at multiple levels. For example, the Signicantly, movement through the sibilities. ey suggest decreased the presence of a normal diet might cular risk factors.” activity of PFK1 is responsible for glycolytic pathway is regulated on Lp-PLA2 activity could be linked to be slowed. While glucokinase activity is Mary L. Chang (mchang@asbmb. important for initiating ux, the most establishing the glycolytic oscillations multiple levels by the enzymes that the increased protein in the modied e authors conclude that “grains org) is publications manager for crucial steps in glycolytic-ux regula- that drive insulin secretion. Addi- function in the pathway and by the diet. Also, because whole grains and should be consumed in a minimally ASBMB. tion are the two fructose steps. ese tionally, the fructose ester products glycolytic intermediates as well as by legumes contain many antioxidants, rened form, and frequent consump- steps, which are carried out by phos- are allosteric regulators of glycolysis, regulatory proteins. the rate of oxidation of molecules that tion of vegetables and legumes should as they can inhibit the FBPases and phofructokinase/fructobisphosphatase Kathleen McCann (Kathleen. isoenzymes to produce fructose ester promote glucose catabolism. [email protected]) is a graduate products, form a regulatory unit. As research in the past 30 years has student in the genetics depart- Both the enzymes that participate continued to demonstrate, the mech- ment at Yale University. in these steps and the products that anisms of regulation of glycolysis are The makings of a honeybee By Rajendrani Mukhopadhyay

Honeybees give us our honey, royal Use your bean (and grain) jelly, propolis and beeswax and sup- Substituting legumes and whole grains for rice can decrease activity port the ecological structure of the environment by transferring pollen of enzyme promoting atherosclerosis between plants. Despite their ecologi- By Mary L. Chang cal and economic importance, very little is known about how honeybee workers develop from embryos to A new study detailed in the August fasting glucose or who had been not kept in check may be linked to adults at the molecular level. In a 2014 issue of the Journal of Lipid diagnosed recently with type 2 diabetes. paper in the journal Molecular & Research suggests substituting diabetes. Participants in one group Also, while no di erences were Cellular Proteomics, researchers whole grains and legumes in place of were allowed to consume their usual observed between the two groups tackled a proteomic analysis of hon- processed, rened rice can reduce the diet dominated by rened rice, while when it came to general measures, eybee worker embryos. IMAGE COURTESY OF MUHAMMAD MAHDI KARIM, A WIKIMEDIA COMMONS USER activity of an enzyme implicated in participants in the other group were such as body mass index and the ey found that while there is a atherosclerosis while also improving instructed to replace rice in their diet energy levels that the participants central set of proteins involved in liquid chromatography combined ity and the cytoskeleton. ese pro- control over blood-sugar levels. with a mixture of black soybeans, reported, levels of the proinam- common biological pathways that with mass spectrometry as well as teins may be present to support early In a study conducted at Yonsei barley and brown rice for three meals matory cytokine interleukin-6 were drive development, “embryos at bioinformatics to see which proteins formation of organs. e late-stage University in Seoul, South Korea, a day for 12 weeks. signicantly lower in the modied di erent developmental stages have were present and how expression embryos, during the 48-to-72-hour researchers randomly split into two Researchers observed signicant diet group. their own specic proteome and changed in embryos during their time frame, produced proteins impli- groups of patients with impaired decreases in fasting glucose, insulin Probably the most important pathway signatures,” says Jianke Li of 72-hour development period. cated in fatty acid metabolism and and other diabetic result of this study? e activity of the Chinese Academy of Agricultural e investigators found that morphogenesis. ese proteins could markers in the modi- lipoprotein-associated phospholipase Science in Beijing. “ese ndings the core proteome of all stages of be responsible for the nal formation ed diet group com- A2, called Lp-PLA2 for short, was provide a vital resource as a starting embryonic development consisted of of organs. pared to the control decreased in the modied diet group. point for further functional analysis proteins involved in protein synthesis, As you can see, the study gives group, indicating that is would explain the increase in and genetic manipulation for both metabolic energy generation and con- researchers an idea of the processes those participants had IL-6 in the control group: Increased the honeybee embryos” and other sumption, development, and molecu- happening at the di erent stages improved control over levels of this enzyme are associ- eusocial insects, such as wasps, ants lar transport. But each embryonic of embryonic development. Scien- blood-sugar levels. ated with increasing levels of several and termites. stage had specic sets of proteins turn tists now can use the data to see if Lower levels of plasma inammatory cytokines. Lp-PLA2 is e investigators studied worker up on top of the core proteome. particular processes lend themselves malondialdehyde, an enzyme produced by inammatory bees, which are responsible for Embryos younger than 24 hours a marker for oxida- cells that breaks down oxidized phos- well to creating genetically modied building the honeycomb, cleaning had more proteins involved in nutri- honeybees, an active area of research. tive stress, also were pholipids in low-density lipoprotein. it, defending the colony, foraging for ent storage and nucleic acid metabo- found in the modi- Lp-PLA2 also is used as a marker in nectar and feeding the larvae. e lism, which could correlate with Rajendrani Mukhopadhyay ed diet group; it has diagnosing cardiac disease. worker bees, all sterile females, rise the cell proliferation that happens been suggested that It is still unclear how Lp-PLA2 ([email protected]) out of fertilized eggs in four stages. at the early stage. Embryos during is the senior science writer and increases in oxidative activity and substantial improvement e rst stage is the egg, during the 24-to-48-hour span expressed blogger for ASBMB. Follow her stress and damage in glucose and insulin metabolism which the body plan of the insect is proteins responsible for cell-cycle on Twitter at www.twitter.com/ rajmukhop. caused by free radicals are linked to diet. However, the established. Li and colleagues used control, transport, antioxidant activ-

12 ASBMB TODAY AUGUST 2014 AUGUST 2014 ASBMB TODAY 13 Issue features research aided by PRIME-XS infrastructure program for proteomics in Europe By Angela Hopp

e August issue of the journal well-established, with several top- Molecular & Cellular Pro- notch research laboratories and several teomics features a substantial col- proteomics facilities operating at the lection of articles describing recent local and national levels. However, research ndings from investigators the European proteomics community supported by the European Union- was not well-organized,” the prologue funded proteomics consortium known authors explain. as PRIME-XS. e EU’s primary funding mecha- For the uninitiated, the acronym nisms for research and development PRIME-XS is short for “Proteomics are known as “framework pro- Research Infrastructure Maximising grammes.” After funding for PRIME- knowledge EXchange and access.” XS was secured under the seventh e consortium’s 12 partner institu- framework’s infrastructure umbrella, tions o er the critical infrastructure – “a major e ort was made to organize specialized instrumentation, expertise the community and to establish a and training — for proteomics coordinated program to provide the researchers in Europe who otherwise European life-science research com- ers are embedded at a site for weeks lack access to such resources. munity with access to top-of-the line or months,” Heck et al. write. “Some e prologue to the MCP special (proteomics) facilities.” users are proteomics novices; others issue was written by Albert Heck of Long story short: PRIME-XS put are experienced researchers who want Utrecht University, Jesper Olsen of out its rst call for proposals in July training and access to novel or special- the University of Copenhagen and 2011 and since then has invited 104 ized technologies that are unavailable Ruedi Aebersold of the ETH Zurich investigators from 21 countries to locally.” (all PRIME-XS principal investiga- carry out work at the consortium’s e ongoing and completed work tors), along with Reinout Raijmakers six access sites in the Netherlands, at the PRIME-XS access sites has of Utrecht University (who manages Belgium, Switzerland, Spain, the U.K. yielded more than 100 publications the PRIME-XS project oce). and France. so far. e 19 new publications in the “Prior to the founding of PRIME- “Sometimes guest researchers stay special issue of MCP describe “a wide XS, proteomics in Europe was already (at an access site) for a single day; oth- variety of proteomics applications in biology and medicine,” Heck says, Submit Your Next Paper to an ASBMB Journal! including antibiotic resistance, plant pathogens, brain malfunctioning, circadian rhythms and quality-control metrics. When you submit a paper to an ASBMB ASBMB journal special features: Heck says submissions for the journal, you can expect: • Customized eTOC alerts MCP special issue were sought openly • Thorough, constructive reviews by scientists • Explore the Editorial Board from “people working in the PRIME- XS joint-research activity programs • Affordable publication charges (*FREE color) • Meet new Associate Editors and researchers from all over Europe • Peer reviewed papers published the day of • Read Collections including: Reflections, who requested access to the pro- acceptance Minireviews and Thematic Series teomics infrastructures.”

Angela Hopp ([email protected]) is editor of ASBMB Today. www.asbmb.org/publications *ASBMB has eliminated color figure fees for members publishing as corresponding authors.

PRIME-XS access site at Utrecht University PHOTO BY BAS VAN BREUKELEN

14 ASBMB TODAY AUGUST 2014 AUGUST 2014 ASBMB TODAY 15 NEWS Report highlights nonacademic careers of STEM Ph.D. holders

arlier this year, the American of which is the increased competi- Black women, Hispanic women and Institutes for Research issued a tion for a declining number of jobs in white women reported working for E report titled “e nonacademic academe. government at the highest rates. careers of STEM Ph.D. holders.” AIR’s report noted the following: • About half of those in nonaca- AIR derived the data from the 2010 • The majority of Asian women demic careers worked in research and Survey of Doctorate Recipients by and men and the majority of white development. Black women, Hispanic the National Science Foundation men reported holding nonacademic women and white women reported and the National Center for Science positions. e other demographic working in R&D at the lowest rates. and Engineering Statistics. We have groups surveyed (black women, His- • About 20 percent of those in reprinted AIR’s key ndings with its panic women, white women, black nonacademic careers worked in non- permission in this issue. men and Hispanic men) were about STEM elds. Black women, Hispanic As a preface to its analysis, AIR evenly split between academic and women and white women reported noted previous research showing nonacademic careers. working outside of STEM at the that more than half of STEM Ph.D. • Most of those in nonacademic highest rates. holders work outside of academe and careers worked for private, for-prot To read the complete AIR report, do so for many reasons, not the least organizations or for government. visit http://bit.ly/1jKL6rt.

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16 ASBMB TODAY AUGUST 2014 AUGUST 2014 ASBMB TODAY 17 CONTINUED FROM PAGE 17

18 ASBMB TODAY AUGUST 2014 AUGUST 2014 ASBMB TODAY 19 NIH UPDATE FEATURE NIH launches a public website for bioscientific 3-D printing By Indumathi Sridharan

he National Institutes of Health’s Users of any National Institute of Allergy skill level can T and Infectious Diseases in June obtain ready- launched a free, public online library to-print les of 3-D printable les called the NIH within min- 3D Print Exchange (or simply the utes either by Exchange). It is the rst government- uploading a sponsored website dedicated to 3-D digital 3-D printing of scientic and medical model le or, models, such as those of bacteria, in the case proteins and anatomical parts. of proteins Visualization of scientic data is a and macro- driver of discovery. Typically, convert- molecules, ing a digital model into a 3-D print- by entering able format is technically demanding the Protein A 3-D model of influenza virus. IMAGES COURTESY OF THE NIH/NIAID. and time-consuming, sometimes Data Bank taking hours even for those who are or the Electron Microscopy Data experienced with it. e Exchange Bank code. Users also can share les aims to leverage the potential of 3-D derived from other open-source printing by saving time, money and modeling software, such as Blender, labor. FreeCAD and the like. e Exchange allows users to Additionally, modeling tutorials, create, upload, download and share illustrated workows and other educa- printable les of their data. “We cre- tional materials are available to help ated this website as kind of a way to novice users build custom 3-D prints. have a YouTube-like experience, but e Exchange also will host online instead of exchanging and sharing forums for sharing tips and tricks, and and commenting on and remixing users will be invited to upload les of videos … we are doing all of those models that can be used for teaching. same things with 3D-print les,” is initiative was directed explains Darrel Hurt, a researcher at by the NIAID in collaboration A 3-D model of influenza hemagglutinin. the NIAID who helped develop the with the Eunice Kennedy Shriver Kaihong Zhou, left, and Jennifer Doudna at the University of California, Berkeley IMAGES COURTESY OF CAILEY COTNER/UNIVERSITY OF CALIFORNIA, BERKELEY Exchange, in a video about the new National Institute for Child Health Indumathi Sridharan (sridharan. site (1). and Human Development and the [email protected]) earned e repository has a wide range National Library of Medicine. More her bachelor’s degree in bioin- of print-ready les, including an information about the Exchange formatics in India. She holds a inuenza virus, an insulin molecule can be found at http://3dprint.nih. Ph.D. in molecular biochemistry from Illinois Institute of Technology, Chicago. She and even a common lab microscope. gov/. did her postdoctoral work in bionanotechnology at Northwestern University and is now an intern at REFERENCE the Office of Technology Transfer at the National Institutes of Health. 1. https://www.youtube.com/watch?v=w3z4BEEUT2s

20 ASBMB TODAY AUGUST 2014 AUGUST 2014 ASBMB TODAY 21 f you had asked Jennifer Doudna Institute, has found herself to be Jamie Cate, and her preteen son are Doudna. “She was full of energy. She a few years ago about the gene- repeatedly sought after as a speaker upstairs in their hotel room pack- had no idea what my research was I editing tool CRISPR, she would and has received numerous accolades. ing to y back to California while about, but she was eager to learn. have described the research as “a Already a member of the National Doudna speaks with me. Friendly She said, ‘If you hire me, I will be pretty small e ort in my lab, just a Academy of Sciences and an Ameri- and warm, Doudna exudes quiet, in your oce tomorrow at 8 o’clock few people having fun checking it can Academy of Arts and Sciences deep-rooted condence. Dressed in unpacking boxes.’ I thought, ‘Wow, out.” fellow, Doudna won the inaugural crisp jeans and a light gray cardigan, this person is just amazing.’ I gave her at was before a lightbulb went Mildred Cohn Award in Biological she speaks thoughtfully, occasionally a chance.” o , before Doudna and her postdoc- Chemistry from the American Society using her hands against the table- toral fellow realized that the bacterial for Biochemistry and Molecular Biol- top to make her points in measured defense system could be exploited to ogy last year (for work she accom- sentences. Aware that she has a highly “I want the lab to be a place where people feel like they x faulty genes or bestow new func- plished prior to the CRISPR craze). successful research portfolio that cov- are all batting for the same team … As I’ve chosen tions on existing genes in all kinds is year, she received the Lurie Prize ers CRISPR, RNA interference and of cells. e small e ort in Doudna’s in Biomedical Sciences from the translational control, I ask how she people to join my group over the years, I’ve always lab at the University of California, Foundation for the National Institutes manages to maintain such a prolic tried to pick those who would foster that kind of Berkeley, has since exploded into an of Health. e annual prize recognizes environment in her laboratory of international one, with laboratories in outstanding work by a scientist age 52 30 scientists. But Doudna is quick environment.” several continents furiously working or younger; Doudna won recognition to reveal her secret – her laboratory – JENNIFER DOUDNA, UNIVERSITY OF CALIFORNIA, BERKELEY on the gene-manipulation possibilities for the work on CRISPR. manager, Kaihong Zhou. “She is the presented by the system. e method type of person who will do whatever has received much attention in the Partnership it will take to make the lab suc- Zhou showed up the next day even mainstream press, including the New It is the morning after the Lurie Prize cessful,” says Doudna. “I owe her a though her paperwork still had to be What is CRISPR? York Times, which described the banquet, a mild spring day in Wash- tremendous amount for what we’ve sorted out in Yale’s human resources It stands for: clustered regularly adoption of CRISPR by researchers as ington, D.C., with a chance of rain been able to do.” department and she couldn’t get paid interspaced short palindromic a “scientic frenzy.” showers, when Doudna and I sit on Fresh out of a postdoctoral fellow- for another month. Zhou describes repeats. Doudna, who is also an investiga- an outdoor patio at the Ritz Carlton ship with Tom Cech at the Univer- herself as restless: “I can’t sit anywhere tor with the Howard Hughes Medical in Georgetown. Doudna’s husband, sity of Colorado, Boulder, in 1994, for more than 20 minutes.” Doudna was starting as an assistant e two women hold each other’s professor at Yale University. Zhou scientic prowess in high regard. “She also was new to New Haven; she has great vision and foresight for sci- had accompanied her husband for ence,” says Zhou of Doudna; Doudna his postdoctoral position at Yale. She calls Zhou “a spectacular scientist.” was searching for a job at the medi- Neither is a procrastinator. If a good cal school, fully acknowledging that idea comes up, the two prefer to set at that time she didn’t know much the idea into action immediately. about biology. Eschewing the human Doudna, describing Zhou and herself resources department, Zhou went as “two peas in a pod,” says, “We con- door to door in the medical school fer on all sorts of things, everything asking faculty members if anyone from who to hire into the laboratory, would be willing to hire her. One how to spend our funds, the kinds of faculty member said he just had lled science projects we’re doing and key his open position for a technician but experiments that need to be done at a recalled that a new faculty member particular time.” was searching for one. He called An ambitious but supportive Doudna to conrm and sent over environment that’s based on team- Zhou’s résumé. work is important to Doudna. “I Doudna failed to see any common want the lab to be a place where scientic ground in Zhou’s résumé people feel like they are all batting for but decided to give her a call anyway. the same team.” e sports analogy Within 15 minutes of getting the call, comes to Doudna easily – her lab Zhou was in Doudna’s oce. “She has a softball team and makes regular trips to Major League Baseball games had these big neon-green glasses on Jennifer Doudna’s laboratory was one of the first to work on the CRISPR/Cas9 gene-editing system. and a very bright dress,” remembers CONTINUED ON PAGE 24

22 ASBMB TODAY AUGUST 2014 AUGUST 2014 ASBMB TODAY 23 CONTINUED FROM PAGE 23 also is hugely important. She speaks of Cate: “I didn’t understand when (although Doudna is fonder of the I was younger the importance of social aspects of baseball than the having the right partner in life. I only actual sport). “As I’ve chosen people realized it later. I now feel I do have to join my group over the years, I’ve the right partner in life, and I’m very, always tried to pick those who would very, very grateful for that.” foster that kind of environment,” she She emphasizes that choosing the says. “For the more senior members right life companion is especially of the lab, they need to understand important for female scientists. “It’s that part of their role in the lab is very important to have a partner who to provide mentorship to younger can understand your passion,” she students.” says. “We’re a little bit crazed. We’re And here is where Doudna says driven by what we nd exciting in Zhou’s presence is important: “She science. I think it’s so important for has maintained the kind of environ- a partner to understand that level of ment where students are pushed to do their very best but are also encour- passion. To make it work between aged to seek help when they need it, career and family, it’s really critical to to understand that they have the sup- have a partner who gets it and is will- port of people in the laboratory when ing to share the burdens.” they run into technical challenges or anything else.” CRISPR: “Small effort” In 2001, UC Berkeley o ered goes big Kaihong Zhou has been Jennifer Doudna’s lab manager for two decades. Doudna credits her for keeping the lab at the cutting edge of research. faculty positions to Doudna and regularly interspaced short palin- In a 2012 Science paper, the Cate, who was at the Massachusetts Doudna always has been interested in RNA. Her research, starting with dromic repeats, because she realized collaborators described how Cas9 Institute of Technology at the time. it was a way for her lab to see how attacked bacteriophage DNA. Two e o er was tantalizing: Doudna work she did with her graduate adviser, Jack Szostak at Harvard Uni- bacteria use small RNA molecules in pieces of RNA generated from the would have a joint appointment to a pathway perhaps similar to RNA CRISPR sequences form a structure the departments of molecular and cell versity, and continued with Cech, has shown over the years that large RNA interference. She and her colleagues that Cas9 uses to nd the comple- biology and chemistry. Plus, Berkeley then could search for any evolution- molecules aren’t a mess of spaghetti- mentary sequence in DNA. Once it is just a ve-minute drive from Law- ary relationships between bacterial like strings. Instead, they are more nds the complementary sequence, rence Berkeley Livermore National and mammalian systems in using the enzyme introduces double- Laboratory, a place indispensible for like proteins with dened, organized RNA to control genetic information. stranded breaks. a structural biology laboratory like structures. Doudna solved the rst Bacteria have three di erent sys- at’s what happens inside a bac- Doudna’s. Furthermore, Doudna’s crystal structure of a large domain of tems involved in the RNA-mediated terium. But one day, while Doudna mother was in Hawaii, so California the protozoan Tetrahymena ribozyme. destruction of invading bacteriophage and her postdoctoral fellow Martin would bring Doudna closer to her. Her group got the rst detailed genomes by endonucleases. e Jinek were discussing some data, they ey accepted. structure of the P4-P6 RNA fragment endonucleases are called CRISPR- both wondered out loud if they could Zhou decided to go with Doudna of the group I intron, which showed associated systems, or Cas. Doudna’s engineer the two pieces of CRISPR- to the West Coast. Doudna’s research the RNA to be packed tightly into a laboratory got involved in studying derived RNA as a single RNA chi- into RNA appealed to her, but Zhou proteinlike globular fold. In 1998, her the type II system when Emmanuelle mera. is chimera could still guide says that their relationship was the laboratory solved the crystal structure Charpentier, then at Umeå University Cas9 to DNA and get the enzyme key factor. Still, it wasn’t an easy of the hepatitis delta virus ribozyme, in Sweden but now at the Helmholtz to cut the DNA as a way of gene decision for Zhou, because she had work that demonstrated how the virus Centre for Infection Research in manipulation. “We looked at each her husband’s career to consider. was capable of hijacking its host cell’s Germany, approached her at a confer- ey decided the move was worth the machinery to replicate itself. other and said, ‘If we link these two ence. “She wondered if it would be RNAs together into a single RNA, we e ort. Zhou was the only person from When CRISPR came onto of interest to us to work together to Yale to move with Doudna. Doudna’s radar in the mid-2000s, her will have a very simple two-compo- gure out what the function of Cas9 nent system that if we could get it to Doudna wholeheartedly gives group was working on gene regula- was,” says Doudna. Type I and III work in other cells, it would be a very credit to Zhou as an equal partner for tion by small RNA molecules in CRISPR/Cas systems use a variety useful tool,” she recalls. “at was the making the laboratory successful. And human cells and RNA interference of endonucleases; type II is di erent turning point.” life has taught Doudna that having a pathways. Doudna became interested in that it relies solely on the Cas9 true partnership in her personal life in CRISPR, an acronym for clustered endonuclease. CONTINUED ON PAGE 26

24 ASBMB TODAY AUGUST 2014 AUGUST 2014 ASBMB TODAY 25 San Francisco, and funded by the Li e environmental beauty and Ka Shing Foundation. e initiative excitement of the islands, which aims to develop genomic analysis included erupting volcanoes, instilled to understand disease processes and a sense of wonder about the natural come up with novel therapeutics. world in Doudna. “ere were so Doudna, who also received a chaired many fascinating bugs, plants – the professorship from IGI, is the initia- natural environment there was so tive’s executive director, with UCSF’s interesting. I was really curious about Jonathan Weissman serving as a what makes a plant look the way it co-director. Although Doudna sees a does. I always felt very drawn to the great future for CRISPR, she says her underlying mechanisms that work heart breaks every time she receives an in biology.” At school, Doudna was email from someone who has a loved drawn to mathematics and science. one su ering from a terrible disease e sense of discovery awed her. She or illness asking if CRISPR can help. recalls always wanting “to be the rst It’s too early to tell, says Doudna, person to know something. at, but the hope is there. Researchers somehow, inherently was attractive still have to work out the ne-print to me.” details, which include guring out Her father was a huge inuence. how to target the gene-editing entities “My dad always fostered a sense of into certain cells and not others in a curiosity in the house,” says Doudna. Jennifer Doudna, right, says that she and her lab manager, Kaihong Zhou, are “two peas in a pod.” whole organism. Her father loved to read about sci- Zhou says that if the pace of ence, lling the house with books CONTINUED FROM PAGE 25 fruit ies, mice, worms and rhesus Doudna’s work was brisk before about science geared for nonscientists; e investigators demonstrated a monkeys. CRISPR came along, she can only when Doudna was in sixth grade, her CRISPR gives Doudna a chance to proof of concept in the Science paper describe it now as hectic. She says the father presented her with a copy of do science with clinical applications. using in vitro systems. In the paper, laboratory used to hold an annual James Watson’s “e Double Helix.” Her hepatitis virus work had a clini- they presciently noted, “Rational potluck, but Doudna’s workload and Her high-school chemistry teacher cal aspect, but the research was far design of chimeric RNAs is robust travel schedule have been so relentless was also an inuence. Doudna, who removed from medical applications. and could, in principle, enable target- that they had to skip the potluck last paid homage to Miss Wong in her Not so with CRISPR. rough an ing of any DNA sequence of interest year. “She’s super busy,” says Zhou. Lurie Prize speech, remembers her academic collaboration with Ho - with few constraints.” “She’s become a celebrity!” being “very encouraging and taught mann–La Roche, Doudna’s group CRISPR isn’t the rst gene-editing kids about the joy of having a ques- is looking to see if the CRISPR/ tion about how does something work tool, but its appeal is in its simplic- Cas9 system can be used to correct Passion and perseverance and setting up an experiment to test ity. All that is technically needed is known genetic defects in neurologi- e possibility of becoming a it.” But it was in 11th grade that the Cas9 endonuclease tagged with cal diseases, such as Huntington’s. scientic celebrity isn’t what drove Doudna discovered what she was an RNA strand, which is simple to “We’ve understood the genetic cause Doudna to science. Biology infused meant to do. “e state sponsored a make in a nucleic-acid synthesizer for a long time, but up until now, her childhood, which she describes as lectureship for people who worked using synthetic chemistry or enzymes. there hasn’t been a good tool for how “a big adventure.” Her father got his at the cancer center in Honolulu on “Researchers have enthusiasti- you might actually x that muta- Ph.D. in English literature from the Oahu to travel around the state and cally adopted this system because tion,” says Doudna. “To me, that’s University of Michigan, Ann Arbor. go to high schools and tell the kids of the relative ease with which you very exciting, because it helps us to When Doudna was 7 years old, what they were doing,” says Doudna. can manipulate complex genomes not only work toward having a direct her father completed his thesis and “We had this wonderful woman – I compared to other similar technolo- impact on human health, but I think moved his wife and three daughters wish I knew her name – who came gies, such as zinc nger nucleases, that when we understand better what from Michigan to take up a faculty from the cancer center in Honolulu transcription activator-like e ector the potential limitations are with position at the University of Hawaii. to my high school. She talked about nucleases, and other more tradi- the current system it will help us as Doudna’s mother, a stay-at-home par- her work on cancer biology and try- tional methods,” explains genomics mechanistic biologists to improve the ent in Ann Arbor who held a master’s ing to understand what goes wrong in expert Joel Gottesfeld at e Scripps tool further.” degree in education, went back to cells that are cancerous compared to Research Institute. To date, scientists CRISPR is also the foundation for school to get another master’s degree normal cells. at just blew me away. have used CRISPR to edit genes in the Innovative Genomics Initiative, at Hawaii, this time in Asian history, I thought that was so interesting. I almost anything they can get their jointly supported by UC Berkeley and began to lecture in the subject at hands on: human cells, zebrash, and the University of California, the university. CONTINUED ON PAGE 28

26 ASBMB TODAY AUGUST 2014 AUGUST 2014 ASBMB TODAY 27 CONTINUED FROM PAGE 27 for experiments gone awry. “Even if something fails, she’ll say, ‘Wow, from absolutely wanted to do that kind of this failed experiment, I’ve seen some- work.” thing really great. Let’s try something Doudna searched for undergradu- else from here,’” says Zhou. “She ate biochemistry programs. “is was never ever once freaked out because in the early 1980s, so there were not something didn’t work.” that many undergraduate colleges Szostak inuenced Doudna in that had biochemistry majors. But another important way. “He would Pomona College in Clairmont, Cali- also tell us students in the lab, ‘Follow fornia, did, so I ended up going there your passion. Don’t worry about your and starting my work in that direc- next career move, because if you fol- tion,” she says. Doudna is the only low your passion and do excellent sci- scientist in the family – one sister is ence all of those career decisions will a teacher who is working on federally become easy to make, because you’ll funded geography projects, and the know what you want to do and what’s other sister is an actress. right for you.’ at was so true,” says Doudna. “It’s really guided me in “When we are sleeping, Jennifer is working.” many moments in my career when I’ve had to make a decision.” – KAIHONG ZHOU, DOUDNA’S LAB MANAGER She respects someone’s enthusi- asm for a particular research avenue, Even though she was inspired to because she knows the enthusiasm study biochemistry, Doudna remem- will help the person persevere. “I bers having doubts while a sophomore think people do their best work when in college taking general chemistry. “It they are very motivated, very excited was hard for me, and I was trying to and passionate about a project,” she understand why balancing equations says. It’s true for her: Zhou describes was going to be relevant to my future Doudna as extremely hardworking, life,” she recalls. At the same time, capable of chipping away at work at she was taking a French class and all hours. “When we are sleeping, Jen- really enjoying it. She approached her nifer is working,” says Zhou. “It’s not French teacher and told her that she surprising to get an email from her at probably wasn’t cut out to do science 5 a.m.” and would be better o majoring in Doudna is grateful that serendipity French. Her teacher wouldn’t hear of also has showed up a number of times it. “She said, ‘I can see you’re passion- in her career. One of those serendipi- ate about it. I know it’s a struggle right tous moments was meeting Zhou. now. But you should stick with it. She emphasizes more than once how at’s going to be a great career path similar they are. “We think on the for you.’ She was right.” same wavelength,” she says. “Our e importance of being passion- goals have always been aligned.” ate about the work was reinforced by Passion and excitement for science Szostak during Doudna’s graduate is something Zhou says she shares training. Szostak “has a mild, quiet with Doudna. But she adds there manner to him, but gosh, he could is something more fundamental to get so excited about science,” says their relationship – trust and mutual Doudna, adding that his enthusiasm respect. “is is why we’ve lasted for Rajendrani Mukhopadhyay ([email protected]) for even the most simple result was 20 years. We never ever say anything is the senior science writer and infectious. unhappy to each other. It’s amazing. blogger for ASBMB. Follow her Zhou says Doudna embodies the People don’t believe it,” says Zhou. on Twitter at www.twitter.com/ same upbeat spirit as Szostak. She’s “We’ve been happy together for 20 rajmukhop. never seen Doudna belittle anyone years!”

28 ASBMB TODAY AUGUST 2014 AUGUST 2014 ASBMB TODAY 29 FEATURE A tale of friendly fruit flies in a jam Author of new children’s book hopes cute and curious cast of characters will ignite appreciation for model organisms By Emily Hu

ight years ago in a cozy co ee “When Ted suggested having an story of a wayward fruit y, Fruity the shop in Nebraska, biochemist animal as the main character (in a wild type, who escapes the clutches of E Ruma Banerjee struck upon children’s book), my mind imme- a vicious yellow jacket and nds her creative inspiration in a rather diately went to the idea of a model way into a band of mist mutant ies Book contributors unlikely subject: Drosophila animal,” Banerjee says. – all named for their various genetic Ruma Banerjee, melanogaster. Various factors, including the mutations. eir peace is short-lived, a professor and It happened during a lengthy approaching 100th anniversary of the however, as that same nasty yellow associate chair at the discussion in the Lincoln co ee shop opening of what is known worldwide jacket discovers the ies and chases University of Michi- with her longtime friend Ted Kooser, as the Fly Room at Columbia Univer- them down. en Fruity and her gan Medical School, studies the poke,” with its mating defect, did approached the ASBMB to discuss the a Pulitzer-winning poet and former sity, contributed to Banerjee’s decision new group of friends must nd a way chemical biology of mammalian not seem appropriate for a children’s prospect of having the society publish U.S. poet laureate who recently had to make the fruit y the central char- out of the yellow jacket’s clutches or sulfur metabolism, the struc- book.) the book. “ASBMB has a serious sci- completed his rst children’s story- acter in a children’s book of her own. perish. tural enzymology of human B12 In the months that followed, ence outreach mission, and publish- book. e two discussed the powerful at book, “Fruity and the Mutants,” tracking proteins and enzymes Banerjee and her son, Rishi, drafted ing a children’s book with a scientic use of animal protagonists in works was published by the American Soci- involved in H2S biogenesis and Making the book a manuscript while Maya, an artist theme is a di erent way of reaching for children, which got Banerjee ety for Biochemistry and Molecular catabolism and redox signal- ough Banerjee does not work on since childhood, painted sample scene into the community,” Banerjee says, thinking about the storied history of Biology earlier this year. ing in immune and neuroim- fruit ies herself, soon after her talk illustrations in watercolor. noting that she had contacted another the fruit y. “Fruity and the Mutants” is the mune function. She earned her with Kooser she spent several months “Our struggles were those that society about the book but was not you might expect for novices – using Ph.D. at Rensselaer Polytechnic reading about them and their uses in met with the same enthusiasm. Institute and completed postdoc- genetic research. In 2007, Banerjee language that was pitched for the “Fruity and the Mutants” debuted elementary/middle school child toral research at the University left her faculty position at the Uni- at the ASBMB’s annual meeting this of Michigan. She is an associate versity of Nebraska and moved to the and illustrating the book well,” spring in San Diego, where Banerjee Banerjee says. “At the end, my editor of the Journal of Biological University of Michigan. For several held a book signing. She also presented Chemistry. years, the idea for the book simmered daughter did a great job with bring- the book at an international children’s on the back burner. ing the book to life with her draw- festival in Michigan in early May. Rishi Ragsdale, She says the book was begun ings, but her rst attempt had the She says it’s her hope that the book, son of Banerjee, is ies looking too true to their insect in earnest during a vacation to as Kooser writes in the foreword, an undergraduate selves, and Ted recommended that Dharamshala, India, in 2012 with “teaches us a little something about at the University of she humanize them.” her children, Rishi and Maya Rags- our world.” Wisconsin-Madison who intends Before painting each scene, Maya dale. “We spent our evenings weaving More information on “Fruity and to major in both physics and used thumbnails and sketches to plan this story and sharing laughs as we the Mutants” can be found at http:// mathematics. the composition and designs. e played with the fruit y names and asbmbchildrensbooks.org/. e book characters went through at least a few Maya Ragsdale, concocted roles for them in the plot,” also is available on Amazon.com. iterations before she found the style daughter of Baner- she recalls. she wanted to stick with. jee, graduated from ey selected a group of mutants Emily Huff ([email protected]) is the University of with names that seemed like they Getting it published the project coordinator for publi- Michigan with a degree in inter- would work in a story for younger cations at ASBMB. She oversaw national relations and intends to audiences, deliberately omitting a Once the manuscript and illustra- the publication of “Fruity and the Mutants.” one day hold political oce. few choices. (For example, “Slow- tion samples were complete, Banerjee

30 ASBMB TODAY AUGUST 2014 AUGUST 2014 ASBMB TODAY 31 ESSAY

of aequorin, an attempt to clone the aequorin gene seemed logical. The amazing green is was before the facile cloning of your favorite gene was a routine procedure in every lab: no polymerase chain reaction; no automated DNA fluorescent protein sequencers; no commercially avail- able plasmids with multiple cloning Events leading to the cloning and expression of its gene sites; no cloning kits; no BLAST, or basic local alignment search tool. and reections on its impact From the partial amino-acid sequence By Milton J. Cormier and Richard O. McCann of aequorin, we were able to derive oligonucleotide probes that were used subsequently to identify putative aequorin clones. IMAGE COURTESY OF SIERRA BLAKELY - WIKIMEDIA COMMONS nly Mother Nature could Institute of Nuclear Studies. While extracts were frozen on dry ice for Aequorea victoria. At about this time, the National construct a molecule whose at Oak Ridge, Cormier and Bernard transportation back to the laboratory Science Foundation grant that sup- even from pBR322, which was an Hole Oceanographic Institution, but O uorescence quantum yield Strehler discovered two of the com- in Georgia. early cloning vector in which inserts he and Cormier agreed to continue ported the Cormier lab was up for approaches 100 percent when dis- ponents required for light emission After moving to Rutgers, Ward, R R renewal, so Cormier submitted a were cloned into either amp or tet their collaboration on the cloning of solved in water (1). is characteristic in luminous bacteria (2, 3). During who continued to collect Aequorea at new grant proposal to support the genes but not an expression plasmid, GFP. of green uorescent protein is the his stay at Oak Ridge, Cormier had Friday Harbor alongside the Cormier cloning work. For the rst time in 25 and that this could be measured in E. Cormier was running out of reason its gene has revolutionized cell the pleasure of meeting many well- group, focused his research on the years, his funding request was denied. coli extracts, given that it is possible to research funds again by then, so he biology. e use of the GFP gene is known scientists from various parts structure and function of Aequorea -18 Fortunately, Cormier had a contact detect sub-attomole (10 mole) levels applied to the NSF. Once again, the responsible for advancing our knowl- of the world as a result of the famous GFP after characterizing Renilla at a major pharmaceutical rm who of aequorin. grant was turned down. is loss of edge of mechanisms in many areas of Gatlinburg Conferences held each GFP at the University of Georgia seemed interested in the project. We suggested Prasher look for funding forced the closure of his lab. cell biology, such as gene expression, year during this time. (4). Charbonneau, who was by then After he presented a seminar to the expression using a bioluminescence Cormier subsequently retired but cell division, cytoskeletal organiza- Starting in the late 1950s, the goal a postdoctoral fellow with Tom company, it o ered generous support assay used routinely in the lab. e insisted that two assistant professors tion, vesicle tracking and neuro- of the research program in the Corm- Vanaman at Duke University, was for the cloning work. very rst try produced so much light be hired to replace him. at was transmission. Moreover, only during ier lab at the University of Georgia determining the amino acid sequence that the luminometer became satu- done. He also remained available 2+ At that point, Cormier began a time when a project was supported, was to understand the biochemistry of the Ca -activated photoprotein looking for a molecular biologist rated. ere was jubilation in the lab. while Prasher continued his work on as a matter of course, because it asked and biophysics of light emission in aequorin (5) using protein puried by who could help clone the aequorin We knew then that we had expression GFP. Fortunately, Prasher obtained an interesting, fundamental ques- bioluminescent marine invertebrates, McCann at UGA. gene. Doug Prasher, then a postdoc of aequorin. at paper was published independent funding in 1989. An tion about the natural world (in this with the major focus initially on the By the late 1970s, members of in the UGA genetics department, in 1985 (8). additional collection of Aequorea was case, “How do marine invertebrates sea pansy Renilla reniformis, which the Cormier laboratory had isolated was interested and agreed to join the made, and the full-length gene was emit light?”) would GFP have been is an anthozoan soft coral common and characterized the three major Cormier lab in the early 1980s. By the Cloning of the GFP gene isolated. at work was published in discovered. along the Georgia coast. proteins involved in bioluminescence time Prasher arrived, everything was Upon completion of our work on 1992 (9). Many of the details leading to During the 1970s, Bill Ward was in Renilla reniformis: luciferase (6), in place for molecular biology, includ- aequorin, Cormier suggested that Based on the protein sequence of the cloning of the GFP gene from a postdoc in the lab. He is now a luciferin-binding protein (7) and GFP ing some frozen Aequorea tissue. at Prasher try to clone the GFP gene, GFP, Frank Prendergast, a profes- the laboratory led by Milt Cormier professor at Rutgers University in (4). It became apparent that we would summer Prasher and McCann went to since we already had a cDNA library sor at the Mayo Medical School in (one of the authors) never have been New Jersey. Harry Charbonneau was never be able to isolate sucient Friday Harbor to collect more jellysh from Aequorea. Furthermore, Ward Minnesota who earlier had published reported. Because of the importance a graduate student at the time and is amounts of these Renilla proteins and, ultimately, construct an Aequo- was willing to furnish us with partial a paper on the characterization of of the GFP gene, we feel that these now a professor at Purdue University in order to study their structure– rea cDNA library. amino-acid sequence data. Prasher Aequorea GFP (10), predicted the details may be of interest to the scien- in Indiana. Rick McCann (also an function relationships required for By the autumn of 1984, Prasher agreed and was successful in isolat- likely GFP chromophore structure. tic community. author) was a technician in the lab bioluminescence. We had to take a Prasher then turned his attention and is now a professor at Mercer di erent approach. felt that he had isolated the aequorin ing a GFP clone. When the gene was to the expression of GFP. University School of Medicine in ere were by then two examples gene based on the hybridization of the sequenced, we realized that the clone From enzymology After making a number of attempts Georgia. of the cloning of genes in higher aequorin-specic oligonucleotides to represented 70 percent of the coding to express the gene, he phoned to molecular biology Over several summers, the three organisms. One was the cloning of several clonal isolates, but he could sequence. Cormier about the diculty he was Cormier began his graduate work of them went to the University of the gene coding for human insulin. not verify this, because he was hav- Since Prasher could not identify having. Cormier assured Prasher that at the University of Texas at Austin Washington Marine Laboratory in So Cormier decided to change his lab ing diculty in expressing the gene. the full-length gene in that cDNA he would gure it out. However, under the guidance of Lester Reed Friday Harbor to collect the biolu- from an enzymology lab to a molecu- We had a conversation about this library, it was obvious that addi- Prasher’s research position at WHOI and obtained his Ph.D. at the Oak minescent jellysh Aequorea victoria. lar biology lab. Since Charbonneau problem. tional collections of Aequorea were was ending. (Had Cormier known Ridge National Laboratory in Ten- In that period, thousands of jellysh had made signicant progress in McCann suggested Prasher might required. At this point, Prasher nessee as a fellow of the Oak Ridge were collected and processed, and the determining the amino-acid sequence be expressing aequorin at a low level obtained a position at the Woods CONTINUED ON PAGE 34

32 ASBMB TODAY AUGUST 2014 AUGUST 2014 ASBMB TODAY 33 ESSAY

CONTINUED FROM PAGE 33 who worked on bioluminescence in ing on the work of John Matthews coelenterates was supported by the (6), now a professor at the Uni- this, he would have urged Prasher NSF, the National Institutes of Health versity of Mississippi, Walt Lorenz Uncovering the unexpected to return to Georgia to complete his and a precursor to the Department of and McCann cloned and expressed work on the expression of GFP.) Energy largely because it addressed a Renilla luciferase (14). is lucifer- By Andrew D. Hollenbach Rather than let the project lan- fundamental question straight out of ase, in tandem with rey luciferase, guish, Prasher gave the gene to Martin natural history: How do these organ- which has a completely di erent Chale and Roger Tsien in 1992 isms emit light? substrate, is now used widely as a upon their request. e rest, as they couldn’t believe it was happening e simple answer is that one reporter for gene expression in cells say, is history. Chale’s lab gured out to me. I’d always worked hard protein with enzymatic activity (lucif- of all types. e use of GFP in all its I learned that it was OK to admit that I had a how to express the GFP gene shortly I and succeeded – not only suc- erase, aequorin) oxidizes a reduced colors is limited only by the imagina- after receiving it. ey then used the ceeded but excelled. Now there I was: problem and accept other people’s help. substrate (luciferin, coelenterazine) to tion of cell biologists. For example, GFP gene to study gene expression in I had just nished my second year of produce blue light. In the organism, uorescence resonance energy trans- living cells. is work was published graduate school, and I had been told journal clubs, presentations and, yes, however, the energy from the excited fer, known as FRET, between GFP ‘A transformative moment’ in 1994 (11). that I had failed my qualifying exam. life. state of the substrate is transferred variants of di erent colors can be When I look back and read what I Tsien subsequently designed I was devastated. e increased expectations and nonradiatively with high eciency to used to measure the distance between wrote for that exam with the eyes of variants of GFP that uoresce in the Not only was this the rst time workload can bring out problems that GFP, which then emits the green light molecules in living cells. experience, I see just how horrible various colors we now use in virtually I had worked hard and failed, but you might never have realized existed. seen when living Renilla or Aequorea Although we outline here events that exam truly was. What I now all of cell biology. e Nobel Prize it also meant that I could be asked Or if you realized these problems are stimulated. is is the same green realize is that it was a transformative committee credited Osamu Shimo- that occurred in the Cormier lab, to leave the program, derailing my existed, maybe you were able to color seen when the original Aequo- moment in my life, a hard realization mura with the discovery of GFP in Frederick Tsuji also has written an dream of becoming a scientist. e control them just enough to survive. rea GFP, expressed as a recombinant that made me reevaluate myself and Aequorea and gave him, Chale and informative article from his perspec- more I spoke with my committee For me, this new stage in my develop- protein, is excited by blue light in a members about why I had failed, rededicate myself to my dreams and Tsien the Nobel in chemistry in 2008. tive regarding the history and cloning ment attacked my self-condence. uorescence microscope. the more I realized that my failure goals. rough the ordeal, I learned e seminal contributions of Prasher of the GFP gene (15). All investiga- I had always su ered from a lack of stemmed not from my intellectual about my shortcomings. I learned to this work were not forgotten by tors who took part in this exciting self-condence (I still do, in fact, but Multiple applications ability but rather from my inability that it was OK to admit that I had Chale and Tsien, however, and that endeavor to clone and express the I know how to manage it now); how- to cope. a problem and accept other people’s part of the story was covered in a long in cell biology GFP gene and the other proteins ever, up to the point when I entered I had thought that sleepless help. I learned how to lick my article in the magazine Discover in Native aequorin was rst injected responsible for coelenterate biolu- graduate school, I was able to deal nights and paralyzing stress were wounds and ght for my 2011 (12). into living cells and used as a calcium minescence should take heart in with this problem, or so I thought. normal for a graduate student. What ambitions. But there is a larger point about indicator by E.B. Ridgway and C.C. knowing that they were part of the e new demands fueled this nega- soon became evident, though, was Many students look at me today the work that led to the discovery of Ashley in 1967 (13). Today, aequo- e ort that resulted in a revolution in tive psychology, fed it like oxygen to that they not only were not normal and see a condent and secure faculty GFP and the ongoing revolution in rin-expression vectors are used to cell biology. a raging re, ultimately leading to but were a serious problem called member. Little do they realize that I cell biology that has been facilitated measure calcium transients in animal, Moreover, as outlined recently by my debilitating and paralyzing panic severe panic attacks; and if I didn’t nearly failed out of graduate school by this fascinating molecule. All of the plant and fungal cells. Joram Piatigorsky (16), those respon- attacks. get the problem under control, and su ered a lot of pain (and a lot foundational research in the Cormier Shortly after aequorin was cloned sible for deciding which research gets Fortunately, I had a stern yet my own psyche would derail my of therapy!) to get to this point in my laboratory and that of the others in the Cormier laboratory and follow- funded, from policymakers to mem- understanding exam committee. To dreams. life and career. Now my experience bers of review panels, should remem- this day, I remember the wise words serves as an example for students — REFERENCES ber that the answers to scientic ques- of the late John Scocca (a man who ‘You must get this to let them know that they are not 1. Ward, W.W. & Cormier, M.J. Photochem. Photobiol. 27, 389 – 396 (1978). tions cannot be known in advance and scared the heck out of me as a student alone, that the hard times they are 2. Cormier, M.J. & Strehler, B.L. J. Am. Chem. Soc. 75, 4864 – 4865 (1953). that these questions and answers often under control!’ but whom I remember now with experiencing will help them realize 3. Strehler, B.L. et al. Proc. Natl. Acad. Sci. USA 40, 10 – 12 (1954). lead to advances in scientic knowl- Graduate school is a whole new stage extreme fondness and the utmost something new about themselves 4. Ward, W.W. & Cormier, M.J. J. Biol. Chem. 3, 781 – 788 (1979). edge and scientic practice that are in a scientist’s development. Gone respect): “You will always be faced 24 and that from these experiences they 5. Charbonneau, H. et al. Biochemistry , 6762 – 6771 (1985). as revolutionary as they are unimagi- are the undergraduate days when with pressures at every stage of your 16 can grow in unexpected ways to 6. Matthews, J.C. et al. Biochemistry , 85 – 91 (1977). nable and unpredictable. you work hard to memorize facts so career. If you want to stay in this 7. Charbonneau, H. & Cormier, M.J. J. Biol. Chem. 3, 769 – 780 (1979). succeed in ultimately realizing their that you can regurgitate them for profession, you must get this under 8. Prasher, D. et al. Biochem. Biophys. Res. Commun. 126, 1259 – 1268 (1985). dreams. Milton J. Cormier (milton. exams. Instead, you are expected to control!” 9. Prasher, D.C. et al. Gene 111, 229 – 233 (1992). [email protected]) is a learn concepts and apply them to Taking these words to heart, I 10. Prendergast, F.G. & Mann, K.G. Biochemistry 17, 3448 – 3453 (1978). distinguished research professor emeritus at the University of real-world problems. e ideas are no began therapy through the student Andrew D. Hollenbach (aholle@ 11. Chale, M. et al. Science 263, 802-805 (1994). Georgia. Richard O. McCann longer someone else’s that you have health program, and over the next lsuhsc.edu), author of the book 12. http://discovermagazine.com/2011/apr/30-how-bad-luck-networking-cost-prasher-nobel “A Practical Guide to Writing a ([email protected]) is an to learn; the ideas are yours that you year I got my panic attacks under 13. Ridgway, E.B. & Ashley, CC. Biochem. Biophys. Res. Commun. 29, 229 – 234 (1967). associate professor at Mercer Ruth L. Kirschstein NRSA Grant,” have to defend. Information comes is an associate professor in the 14. Lorenz, W.W. et al. Proc. Natl. Acad. Sci. USA 88, 4438 – 4442 (1991). University School of Medicine and control, which allowed me to dem- genetics department at Louisiana State University 15. Tsuji, F.I. Microsc. Res. Tech. 73, 785 – 796 (2010). director of the graduate program fast and furious, and you are expected onstrate to my examining committee in biomedical sciences. Health Sciences Center in New Orleans. 16. Piatigorsky, J. Perspect. Biol. Med. 53, 571 – 583 (2010). to balance class, laboratory work, my true capabilities.

34 ASBMB TODAY AUGUST 2014 AUGUST 2014 ASBMB TODAY 35 EDUCATION Curricular revision: embracing the journey By Neil Oshero

ew words strike as much fear centered teaching. that I had with the directors of the in the hearts of medical-school e Vanderbilt University School anatomy course (which ran simul- F faculty members as “curricular of Medicine has undergone two taneously with biochemistry) was revision.” It is a long, arduous and major curricular revisions since 2007. when they sent an annual message often unsettling process. However, e rst (now referred to in the local telling me when the anatomy exams curricular revision is a phrase that vernacular as Curriculum 1.0) seems would be and to make sure that I did many, if not most, of us are hearing relatively mild by today’s standards; not schedule the biochemistry exams these days. however, it seemed earth shattering at too close to those dates. In those A large number of medical schools the time. at was when we moved days, medical student courses were have revamped their preclerkship from discipline-based courses to important to departmental missions, curricula over the past decade, and interdisciplinary blocks. After direct- because they provided departments many are in the process of doing so ing the medical biochemistry course with an identity within the School of now. It is a trend that is being driven for 17 years, I had to work with two Medicine. Although it had become at the national level. Commonly, new faculty members from other depart- harder to dene what a biochem- curricula are marked by a move from ments to develop a new course that ist actually was, everyone knew a discipline-based to interdisciplinary encompassed biochemistry, cell and biochemistry course when they saw courses, by decreased time devoted tissue biology, and genetics. it. Discipline-based courses also to the foundational sciences, by the Prior to Curriculum 1.0, the gave course directors a certain level devaluation of lectures and other preclerkship science courses, which of status within their departments. of the classes. I lined up the lectur- together. After all was said and done, grown enormously. traditional teaching methodologies, were run out of departmental oces, Directors had a time-consuming and ers for biochemistry (blue) and my Molecular Foundations of Medicine In 2011, only ve years into and by the inclusion of small-group had little to do with one another. often thankless job, and most faculty co-directors lined up the lecturers was far better than any of the courses Curriculum 1.0, we learned that we sessions and other types of learner- For many years, the only interaction members were grateful that the for cell and tissue biology (red) and that it replaced; it allowed us to place would be moving to a new model, responsibility for the course rested in genetics (green). Once we had every- important scientic information into Curriculum 2.0, starting in autumn someone else’s hands. one scheduled, I changed the color a more logical, appropriate and mean- 2013. is time around, I had greater After the initial shock of our scheme to denote the type of class: ingful cellular context. responsibilities. In addition to being mandate for Curriculum 1.0 wore o Blue now stood for lectures, red for e block turned out to be a a block director, I was one of four (along with all of the now-familiar exams, green for patient sessions and startling success with the medical faculty members charged with devel- questions: Why are we doing this? so forth. students, which was music to my oping, implementing and oversee- What was wrong with the old cur- “at was the day that everything ears after so many years of running ing the entire preclerkship science riculum?), we settled into our task. changed.” biochemistry, “the course that all curriculum. e task was daunting, Our rst foray started with three Although altering the color scheme physicians loved to hate.” I found it especially in light of the far more coordinated semi-independent seemed like a minor modication at much more rewarding to teach as a radical (or cutting-edge) demands of courses. We soon abandoned this idea the time, it turned out to be a pivotal member of a faculty team than to go Curriculum 2.0. and decided that it would be best to point in the development of Molecu- it alone. Faculty members from other We had to decrease the preclerk- work together rather than as separate lar Foundations of Medicine and in departments and administrators soon ship time for the foundational sci- entities. After several months and my development as an educator. e became my colleagues and valued ences from two academic years to one many di erent approaches, we arrived block became more than the sum of friends. For the rst time, I felt that calendar year with a later reintroduc- on a mutually acceptable interdisci- the individual disciplines. We stopped I could translate the creativity I put tion of the foundational sciences plinary schedule and christened our caring, for instance, whether a lecture into my research into my teaching. in the clinical years. Moreover, the new course Molecular Foundations of on membranes was cell biology or Although my value to the mission of individual science blocks were much Medicine. To help set up the block, I biochemistry and started caring more my department had diminished, my IMAGES COURTESY OF VANDERBILT UNIVERSITY AND MEDICAL CENTER generated a color-coded spreadsheet about how everything in the block t value to the mission of the school had CONTINUED ON PAGE 38

36 ASBMB TODAY AUGUST 2014 AUGUST 2014 ASBMB TODAY 37 MINORITY AFFAIRS

CONTINUED FROM PAGE 37 e successful implementation of the curricular more heavily integrated with one another than in the previous curricu- revisions at Vanderbilt required a strong Q&A with Pumtiwitt McCarthy lum. My eight-week Molecular Foun- dations of Medicine block morphed working relationship between the faculty and the By Andrea Anastasio into a six-week Human Blueprint administration. Each group valued the other as an and Architecture block that included several hours of pathology, anatomy educational partner. Tell us about your current How did you first become of minorities entering science, tech- and pharmacology in addition to its position. interested in science? nology, engineering and math elds. previous core elements. Furthermore, rst year of Curriculum 2.0. By all tributor to our success and serves as My advice is to seek out mentors who the blocks contained less time for accounts, it has been very successful. a model for how administration and I completed my I can remember being interested in are in the position you want to be in lecture and a featured unifying thread Initial evidence suggests that students faculty members can work together postdoctoral the way things work even at a young and learn from them. I also would say of weekly small-group sessions that who have participated in the cur- on critical projects. fellowship at the age. I distinctly remember a time work hard, never give up and always taught the sciences in the context of riculum are scientically inquisitive, I am looking forward to our next Center for Biolog- when I broke my parents’ record take the opportunity to learn from patient cases. ese case-based learn- display strong reasoning and team- major curricular challenge: the inser- ics Evaluation and player because I wanted to gure out your mistakes. work skills, and can e ectively apply tion of the foundational sciences into Research at the how all its parts worked together. I ing sessions were critical to the success MCCARTHY of Curriculum 2.0 and were allocated these underlying scientic concepts the clinical curriculum. I am already Food and Drug really developed a love for science Do you have any heroes, when I had the opportunity to do six hours a week of in-class time. to clinical scenarios. certain regarding one aspect of the Administration on the National Insti- heroines or role models? If Despite the complexities of Cur- e successful implementation of process: If we want our students to tutes of Health campus in Bethesda, research as an undergraduate. riculum 2.0, our experiences with the curricular revisions at Vanderbilt reinvest themselves in the biosci- Md., last July. e following August, so, describe how they have Curriculum 1.0 prepared us for the required a strong working relation- ences while on the wards, we cannot I started as an assistant professor of Were there times when you influenced you. ship between the faculty and the chemistry at Morgan State University interdisciplinary and collaborative separate the science from the clinical failed at something you felt My mother is my heroine. She immi- administration. Each group valued in Baltimore. I am teaching courses, approaches necessary to develop the experience. We have to repackage grated to America from Liberia in the the other as an educational partner. establishing a research program and was critical to your path? science blocks in a model that was the foundational sciences in terms of late 1970s. She had a very good job Although the administrators estab- serving on university and department e transition from high school to unique to Vanderbilt. In contrast their patients’ illnesses, symptoms, back home but essentially had to start lished the guardrails for and oversaw committees. My research program is college was particularly dicult for with the curricula at many other test results and treatments rather than all over in America. She was hard- our curricular revisions, they did focused on gaining a better under- me, and I had to take a step back and medical schools, Vanderbilt’s Curricu- in terms of the traditional disciplines working, humble and respectful to not micromanage the process. ey standing of enzymes that produce reassess what was working for me lum 2.0 deftly incorporated a variety that once dened our teaching. Pilots everyone she encountered. She always trusted the faculty members to imple- capsular polysaccharides in the patho- and what wasn’t and make appropri- of teaching modalities and valued of such integrated courses show told me, “To whom much is given, ment a creative and appropriate set of gen Neisseria meningitis, one of the ate changes. is made me more them all. Students, according to their promising results. much is expected.” I try to remember science blocks. is trust allowed the leading causes of bacterial meningitis. determined not to be dened by my block evaluations, greatly appreciate Finally, although our two cur- that I have been blessed and give my faculty members to take ownership of past failures but instead by what I this approach. ricular revisions have had a profound all to whatever I do. We now have completed our their blocks, which was a critical con- e ect on the way that we teach our What are the key have succeeded in. I think failures and disappointments are, of course, medical students, in many respects experiences and decisions What is it that keeps you they have had a more profound e ect unwanted but necessary. It is through Need help with curricular revision? on me. By embracing the journey you made that have helped these disappointments that I can working hard and studying rather than ghting it, I have gone you reach your current appreciate and be grateful for how far science every day? If your department or institution requires assistance with curricular I have come. revision; the adoption of new teaching methods; or the development of from being a teacher to an educator position? I would say my desire to be a lifelong to an educational leader and have learning objectives, assessment items or competencies, the Association of I had great mentors as an under- learner. I want to always keep grow- written a new chapter in my three- What advice would you Biochemistry Course Directors can help. graduate student, graduate student ing and continually improve. My decade academic career. give to young persons Founded by the Association of Medical and Graduate Departments of and postdoc. ey were encouraging ultimate wish is to instill a love and Biochemistry in 2008, the ABCD is a membership organization of nearly from underrepresented understanding of biochemistry in my Neil Osheroff (neil.osheroff@ and supportive, which really helped 300 biochemistry (and related) faculty members from about 170 schools students so that they see it as a eld vanderbilt.edu) is a professor of me to gain more condence in myself backgrounds who want to of medicine, dentistry and pharmacy. ABCD members are educational that is accessible to them and one biochemistry and medicine and and my scientic ability. is con- pursue careers in science and curricular leaders who have tremendous experience and expertise in holds the John. G. Coniglio chair dence led me to seek out and go after they can pursue. all aspects of curricular design and integration, learner-centered teaching in biochemistry at the Vanderbilt similar to yours? University School of Medicine. He is a master sci- opportunities that I otherwise would modalities and educational scholarship. ence teacher, a founding member of the Academy not have pursued. I also think devel- I am honored and proud to be at Andrea Anastasio (aanastasio@ If you are involved in teaching the molecular sciences to professional for Excellence in Teaching, and has led a National oping my skills outside the lab, such Morgan State University, which is a asbmb.org) is the ASBMB’s students, consider joining the ABCD. Faculty members at all levels of Institutes of Health-funded research program for as writing, serving on committees and historically black college or university, education and diversity program experience are encouraged to apply for membership. For more informa- the past three decades. He also chairs the execu- assistant. tive committee of the Association of Biochemistry giving presentations, has made me so that I can hopefully help make a tion, visit www.abcd.wildapricot.org. Course Directors (www.abcd.wildapricot.org). more well-rounded. di erence in increasing the number

38 ASBMB TODAY AUGUST 2014 AUGUST 2014 ASBMB TODAY 39 PROFESSIONAL DEVELOPMENT

said she also valued her service on Networking ing, then try to think of it more as various committees. data gathering and an exchange of e webinar speakers discussed McNutt said that she would have ideas like a research collaboration. Looking beyond the lab networking at the most length, and I honed her people skills – how to Also, Goel notes that networking cannot stress its importance enough. motivate people by recognizing their includes helping others out. AAAS webinar highlights paths to nonacademic careers “Networking is the foundation for strengths and weaknesses, bringing In the end, McNutt made an making the right connections, build- them together to work as a team, and excellent point: “always build bridges By Shaila Kotadia ing personal relationships with people, assigning tasks that they will excel at along the way; never burn them.” You getting your name and work out and be comfortable with. never know where someone will end there,” McNutt said. Nowadays, with If you do not feel ready after grad- up or how he or she can help you, so he new normal is that most women in science. e personalities so many scientists and publications, Educate yourself uate school in these areas, consider always be respectful and courteous. Ph.D.s will have nonacademic had been organized into a triangle, networking is the best way for some- One takeaway from the webinar is taking a postdoctoral fellowship. As positions. Nowadays, jobs in with the points designated as the No matter what you do next, it is T that when you’re choosing a gradu- one to connect you with your work. Conlan said, “A postdoc is a neces- going to be “like jumping o a cli ,” nonprots, government, industry, leader, the loner and the follower. Conlan talked about informational ate school or postdoctoral position, sary career step for some people, not a says Conlan, because you will not patent law and many other areas “is professor called me breath- interviewing, which is a great way to you should seek out institutions with holding pattern.” have any idea of what it is like until employ newly minted Ph.D.s. But lessly to tell me that I was her Joan build your network. When contact- career-development oces or grants you are in the thick of it. If you keep how does a budding young scientist of Arc because I had fallen on the ing individuals in elds of interest, be that allow Ph.D.s to intern at other your network open, you always can transition to these careers? As I was midway point between the leader and Transitioning to prepared to ask better questions by organizations. use that as an opportunity to transi- searching for my next step, advice the loner,” McNutt said. “Basically, a new marketplace recognizing your skill sets and nding For those already stationed some- tion back to a previous career or onto from those that had experienced the she said I was the person who would the jobs that best match those. where, Conlan suggested looking to Goel has made the jump to a new the next. transition was priceless. lead the troops into battle, but if they Prepare to cover four basics: neighboring institutions that o er career twice and said he did his home- A career outside of the lab can Earlier this year, when I was look- wouldn’t follow me, I would just do • the present – what the interview- programs if your current institution work beforehand. It is important to be fullling and prestigious and can ing for my next professional position, it myself.” ee’s current position entails does not. In addition, she says that seek out all of the options that exist lead you on the road to a happy and I had the chance to view a webinar Conlan described her path as • the past – the path the person the myIDP resource provided by Sci- and to be able to step out of your successful life. Now is your chance to (now a members-only privilege) pre- “planned happenstance.” She said, took and whom he or she spoke with ence Careers is an excellent resource comfort zone. In the end, you need to explore and nd what job ts your sented by the American Association “Looking back on it, it looks very on the journey to match your skills, values and inter- nd what best ts you at that time. best attributes! for the Advancement of Science titled planned, but at the time it seemed ests with possible career paths. McNutt added that she • the future – where the person is “inking outside the lab: nding a like a random walk.” McNutt added that you should approached every job as the job she headed and where the eld is going fullling nonresearch career.” A panel e constant in this walk was her Shaila Kotadia is the education push for nonacademic career speakers would have for the rest of her career. • advice – who else you should and outreach manager for the of speakers with mixed experiences e ort to highlight careers outside of for seminars. With this strong work commitment, talk to and career opportunities that Synthetic Biology Engineering that led them to positions outside of academia while she was in graduate she moved forward in her career to might be available Research Center (Synberc) at the the lab relayed their personal journeys school and during her postdoctoral Sell yourself many leadership positions. If you are intimidated by network- University of California, Berkeley. and the necessary skills they devel- training. is helped her obtain a oped along their paths. e webinar position at the Science Alliance at the But what about that frustrating loop was full of gems that are crucial when New York Academy of Sciences and of needing experience to get a job navigating the career world away her current job at the NIH. but not being able to get a job due to from the bench. Here, I recap some Goel began by saying, “I like to tell lack of experience? Goel says that you NATIONAL POSTDOC APPRECIATION WEEK of the major points. people that I’m actually on my third have more experience and skills than e panelists included Marcia career now.” He said he began as a you might think. Being able to think McNutt, editor-in-chief of Science graduate student — delaying the pro- critically about issues is important for magazine; Lori Conlan, director at cess of facing the real world. He kept many careers. ink hard about how the National Institutes of Health his eye out for opportunities even if you are selling yourself. Oce for Postdoctoral Services; and they were outside his comfort zone Develop your skills Anish Goel, director of geopolitical and found the AAAS Science and Celebrate Your Postdocs! a airs at e Boeing Company. Technology fellowship. After working If you are already in a position meant McNutt started on a traditional for the government, he decided that to develop your skills, consider also Join the National Postdoctoral Association in academic path, even obtaining tenure he would switch to the private sector, gaining new experiences. celebrating its fth annual National Postdoc at the Massachusetts Institute of landing eventually at Boeing. For instance, Goel said he would Appreciation Week (NPAW) Sept. 15-19. NPAW Technology, but decided to switch e webinar continued to be a have practiced nonacademic writing is a chance for you and your institution to celebrate careers and accepted a position as a goldmine of advice for a scientist and presenting to large groups of peo- the achievements and contributions of your director of a small, not widely known looking to transition to a nonaca- ple by giving speeches. Conlan said postdoctoral scholars and researchers. oceanographic research lab. demic career. Below are several high- that she would have developed oce She said that she had taken a per- lights from which anyone on the job skills by volunteering at nonresearch For more information, visit: http://nationalpostdoc.org/index.php/meetings-and-events-4/appreciation sonality test for a university study on search can benet. oces at her home institutions. She

40 ASBMB TODAY AUGUST 2014 AUGUST 2014 ASBMB TODAY 41 PROFESSIONAL DEVELOPMENT

other academic leaders, meetings of exceptions for hardships, and other ing. Analyzing course and program subcommittees that I lead, meetings similar student issues. enrollments to see where we are Moving into administration: over lunch, meetings over breakfast, I also oversee admissions, recruit- experiencing growth in our schools, and more. ing and program advertising and predicting where we need additional marketing – areas in which most faculty members, creating additional Ben’s story faculty members (other than those oce and lab space (sometimes out of Is it really that difficult? who specialize in these areas) have utility closets), and looking for new My situation is very similar to Mary’s. By Mary Hu and Benjamin D. Caldwell I have just completed my second year little experience. ways to enhance programs is reward- as dean of the graduate school. In general, I do enjoy my role as ing. It is nice to know and meet Like Mary, I attend a multitude dean, mostly because I get to interact faculty members who show passion for their disciplines, and the enthusi- of meetings. I serve on a number of with all kinds of people across our asm they exude for their programs is Editor’s note: is is the second and research. Also, newcomers could would continue teaching 10 to 12 standing committees that meet regu- campus as we build new programs for inspiring. article in an occasional series about bring in fresh perspectives and ideas. credit hours per year while perform- larly (weekly, biweekly or monthly). our students and our community. We both have come to realize that transitioning from the faculty ranks We both have been in our posi- ing those mysterious administrative is can create scheduling night- administrators and faculty must work into university administration. In tions for about two years now, and duties. We told ourselves that teach- mares, and I worry about the time In conclusion together to support the overarching we both split time between our ing and having daily interactions with I have available for students in my Over these past two years, we both February, Benjamin D. Caldwell, goals of our universities and that we administrative and faculty roles. We department colleagues would make us classes and labs. Time management have learned that, while the work that dean of the Missouri Western State all value the success of our students. both love teaching at the undergradu- di erent from the other administra- and organization have been essential we do as administrators is very di er- University Graduate School, wrote Helping to shape that vision, resolv- ate level. Sharing our passion for tors: We’d be faculty members with and, at times, challenging! ere are ent from what we do in a classroom, about the routes to administrative ing problems that can hinder the biochemistry and watching students only one foot on the dark side, and times when both students and faculty it is not necessarily dicult. It takes positions, how the transition aects become lifelong learners are just two we could save ourselves if we began to university’s success and knowing that members have diculty tracking me organization, an eye for detail and a of the highlights of being involved in approach a point of no return. we share a common goal has been a relationships and duties, and other down. Am I in my faculty oce or commitment to meeting deadlines, undergraduate education. truly transformative experience. considerations. Here, Caldwell and at the graduate-school oce across which can add a level of stress. It also Mary Hu, assistant dean of Bellar- Mary’s story campus? (I am getting more exercise requires patience, strong listening So why’d we do it? Mary Huff (mhuff@bellarmine. mine University’s College of Arts and My journey began two years ago. My going back and forth across campus!) skills and the ability to work with all edu) is assistant dean of Bellar- Sciences in Kentucky, explore shared Honestly, the idea students often tell me that they can Like Mary, I’m responsible for types of personalities. mine University’s College of Arts experiences as administrators at of moving to what tell that I am busy but that they have monitoring student registration, Some of the work is routine; yet and Sciences in Louisville, KY. many faculty mem- no idea what I’m doing. I am not sure course o erings and faculty-member then there are projects that are at the Benjamin D. Caldwell (caldwell@ regional institutions. Caldwell and missouriwestern.edu) is a profes- bers refer to as “the that I can easily put into words what Hu also act as regional directors for assignments. However, I dedicate heart of the position that are enjoy- sor of chemistry and dean of the dark side” had never I do either! the American Society for Biochemis- a lot of time to overseeing student able. Our universities are both in Missouri Western State University appealed to either One major focus is course schedul- complaints about grade assignments, a period of growth, and helping to Graduate School. try and Molecular Biology’s Under- of us. While we ing. I review all of the schedules as requests for course substitutions or implement the strategic plans is excit- graduate Aliate Network. didn’t really know they are developed and make sure what administrators that there is enough variety. I also t institutions like ours, the did, we long had work with the school registrar to administrations tend to grow believed that they maximize classroom space. When

A their own – developing faculty served to create more work that hin- registration begins, I monitor the and promoting from within. dered faculty members like us from schedule to make certain that we have The Florida Biomedical Career Symposium One good thing about this doing our jobs! Why would anyone enough courses and cancel those with approach is that those who are want that type of position? insucient enrollment. November 7, 2014 selected for administrative positions On the other hand, it was at- I also oversee textbook orders each know the institution, faculty mem- tering to be o ered positions with semester, working with faculty mem- KEYNOTE SPEAKER: Supported by The Scripps Research Institute, bers and students. When an institu- new responsibilities. And, having bers and the bookstore sta ers. Sir Harold W. Kroto Florida and the American Society for tion lls administrative positions with great respect for our own deans and en there are the other duties, Co-recipient, 1996 Nobel Prize in Chemistry Biochemistry and Molecular Biology Career external candidates, it can take some administrators, we knew that working such as mentoring new faculty mem- Francis Eppes Professor Symposia Program time for these new employees to learn Department of Chemistry and Biochemistry with them would be a good experi- bers, overseeing the faculty-devel- Florida State University the systems and culture of the institu- ence. So we decided that it was time opment budget, approving student tion before getting down to business. to leave our comfort zones and see if internship applications, reviewing KEYNOTE LECTURE TITLE: On the other hand, one potential there was a di erent way to make an student petitions and sometimes The Global Educational Outreach for Science, Engineering and Technology downfall to promoting from within impact at our universities. listening to student complaints. is that it takes successful faculty (GEOSET) Project Pioneered from e beauty of both of our o ers is Of course, there are endless meet- Florida State University members away from areas in which that they were not going to remove ings: meetings with the dean, meet- they have excelled, such as teaching us from teaching. In fact, we both ings with the chairs, meetings with

42 ASBMB TODAY AUGUST 2014 AUGUST 2014 ASBMB TODAY 43 OUTREACH

ASTC members are mostly with these communities, like your to gaming. from museums and own, is that often people just aren’t Sacco: I’ll also just add that, from The CAISE for informal aware that there is accumulated the informal educators’ side, we science centers, right? wisdom from the work that has always hear that they’re really eager been done over the past almost 50 to connect with scientists and to Bell: Correct. And, as they are an years and funded by NSF for over get access to cutting-edge research anchoring sector for the eld, it’s a science education 30 of those. (A) People don’t know and resources that are coming out perfect place for us to be. But (the about it, and/or (B) they might not of people’s education and outreach CAISE) project is meant to serve as Open repository o ers thousands of project and activity descriptions for use understand the term. “Informal sci- branches of their labs and university much of the broader informal STEM ence education,” frankly, puts some departments. So there’s a two-way by scientists and students interested in engaging new audiences in their work education eld as we can in addi- people o , because they feel like it need there. tion to those – so zoos and aquaria, By Angela Hopp connotes less serious … And perhaps nature centers, afterschool, media, it’s an unfortunate term, but really it’s How are projects and citizen-science programs. Part of our only meant to distinguish between in cooperative agreement from the very school and out of school. activities organized in this he Association of Science and creative the enterprise was – (it was) Berkeley. While I was there, I ended beginning with NSF is that we must Hunt: I would repository? How should Technology Centers, a Washing- an experience that I did not have as up getting involved in a whole bunch always strive to create resources for add that these ASBMB members go about T ton, D.C.-based membership a student in K – 12. I just was not of di erent departments and programs. and connect all of the ISE sectors to kinds of projects organization, is home to the Center engaged: It might have been the I started working in the education cultivate and strengthen the sense of a and activities are digging into it? for the Advancement of Informal teachers; it might have been me … department doing summer classes professional eld. becoming more Sacco: Every record in our reposi- Science Education, a National It was through unique learning and after-school classes for kids of all integrated into the tory — and there are almost 9,000 Foundation of Science–funded center experiences and a relationship with di erent ages. And when I graduated, I understand that CAISE’s HUNT scientic process. that houses a repository of informal an informal institution that I changed I started working there full time. I was of them now — is tagged with a set website offers a It’s no longer something that’s for a of metadata, and you can use that science-education projects and related my career trajectory and began run- half-time in the research department, select few dedicated individuals who metadata to search and sort di erent professional resources. ASBMB ning programs and redirecting my doing research and evaluations of dif- searchable database of like doing it. But it’s becoming a part records. e big bucket categories Today’s editor, Angela Hopp, talked education trajectory so that I could ferent STEM learning programs, both of the NSF grant process, a part of informal-education that records are sorted into are these: to two CAISE sta ers: James Bell, the continue working in this eld, which formal and informal, and then half- the (National Institutes of Health) • Funding source — Which federal project director and a principal inves- I’ve been doing since then. time as the manager for a national activities. Tell me why or process … And this (repository) is a agency or private foundation funded tigator, and Kalie Sacco, the program Sacco: I started after-school organization called the how you think it might be way to say, “Hey, don’t worry. We’ve the project or piece of research or and community manager. e Ameri- getting interested Coalition for Science After School. I got this covered based upon all of useful to ASBMB members. evaluation? can Society for Biochemistry and in museum educa- was explicitly interested in museum these years of experience,” which you • Content — What is the science Molecular Biology’s outreach coor- tion specically education – not necessarily science – Bell: If scientists, directors and their guys are accumulating on the site. topic or discipline? Your members dinator, Geo Hunt, also joined the and working in but working at the (Lawrence Hall of students — and sometimes those peo- Bell: Right. e broader-impacts might go look for records that fall discussion. is transcript has been museums when I Science) was fun. ple in the role of designing outreach criterion for the NSF-funded projects SACCO under the life science metadata tag. edited for length, style and clarity. was an undergrad I guess, like Jamie, I didn’t have or engagement experiences — are has been given a new focus … to • Audience — Who is the record in college too. I started at a chil- a lot of great experiences in formal looking to develop activities to engage re-elevate it to equal importance with for? And that’s for both learners — Can you tell me about your dren’s museum and an anthropology science education growing up. I was the public, or any audience, in the intellectual merit. In order for scien- elementary school children, adults, backgrounds? museum in the Bay Area and then in a small town. ere was no real big scientic content of their research, tic research to get funded, it has to took a class up at the Lawrence Hall science museum. So coming at it as a they have a lot of di erent options have the support of society. is is youth, etc. — as well as the profes- Bell: I’ve been in of Science, which is a science center in young adult was really exciting for me. available to them. ey can go to the theory of action, right? To have sional audience — a scientist or an informal science a school and try to do something the support of society, people have to undergraduate or graduate student. education for with a (class) or teacher. ey can go understand why it’s being done, what • Resource type — That tells you almost 30 years. online and look for activities ... ey the benets of it are, who it’s for, and what you’re looking at — whether it’s I started after can develop things out of their own how rigorously and thoughtfully it’s an evaluation report, a peer-reviewed having initially heads, which they often do. being conducted. research paper, project description, BELL a music degree. I guess the point we’d like to And so these broader-impacts presentation, etc. When I nished my undergrad, I make … is there’s this whole body criteria — which are projects like the • And the last thing is environ- was volunteering at a place called of knowledge and a repository of ones we try to catalogue and make ment type. at’s the learning setting the Exploratorium in San Francisco, … examples of ways to design those accessible — help people commu- in which the record you’re looking at a science center. And through my experiences based upon evaluation nicate, engage the public and other takes place … like after-school pro- exposure there to a very di erent and research and years of experience audiences through these variety of grams, broadcast media, conferences, exhibitions, etc. way of teaching and learning science, IMAGE COURTESY OF RISDON PHOTOGRAPHY of what works and what doesn’t. strategies — from exhibits to citizen- I (made) a career shift ... e way CAISE convenes informal STEM education professionals at the 2012 ISE PI Meeting to discuss and advance What we’ve found as we interact science projects to television to lm CONTINUED ON PAGE 46 things were done there and how ideas for better learning designs, settings and research.

44 ASBMB TODAY AUGUST 2014 AUGUST 2014 ASBMB TODAY 45 CONTINUED FROM PAGE 45 to know that some relatively well- informalscience.org is an email known science programming has been address that both Kalie and I receive. You have both mentioned funded by the NSF ISE program. I And we are here every day. You can the media. What are know this isn’t in the biology sphere, get a really quick response and help some examples? but Neil deGrasse Tyson’s original with guring out how you can use the radio show, “StarTalk Radio Show,” resource and/or contribute to it. Bell: It’s projects at public media sta- was funded through the ISE program. Sacco: Exactly – our willingness to tions, for example, that were funded, NOVA has been funded by the ISE help people navigate the website and say, by the NSF to achieve public and AISL program at the NSF. A our eagerness to help your readers engagement and learning goals via an whole variety of other science shows connect with the ISE resources that innovative approach. One primary on PBS have been funded by the NSF. we have and also to learn from what example … is the KQED (program they’re doing. called) “Quest” in San Francisco. Is there anything else Hunt: In my eyes, CAISE is the ere’s a public media station, and premiere online resource for scientists they partner with 16 other organi- you feel ASBMB members looking to get involved with science zations locally, some of which are should know about CAISE’s outreach and informal education. It An open letter to press science museums, science centers and makes my job much easier! children’s museums, but others are online project repository actual labs that have outreach oces, or informal science Angela Hopp ([email protected]) all of whom contribute to multimedia is editor of ASBMB Today. officers who won’t promote stories that Quest produces on local education in general? science-related issues. Bell: If they have any questions or Sacco: You might be surprised want to contribute anything, caise@ unembargoed research papers By Angela Hopp

Author’s note: While this letter is ear press ocer who won’t change or save lives. We have the addressed to press ocers who won’t promote unembargoed research courage to reveal our own wonder promote research papers that cannot D papers, and ignorance to scientic experts be embargoed, it raises an important I know we haven’t met and it’s with the hope that the answers to our questions will increase scientic issue that scientists should under- upsetting when strangers wag their ngers, so let me begin with a bit literacy. We want to showcase the stand. A news embargo ensures that about how much we have in com- expertise and creativity of research- certain information is not made mon. ers, because it’s what we’re paid to do, public until an agreed upon time. I wear multiple hats here at the scientists aren’t very good at doing it Some scholarly publishers use embar- American Society for Biochemistry themselves, we like helping people goes to keep newly accepted research and Molecular Biology. My primary and we’re good at it. Most impor- papers out of the public sphere until job is as editor of this magazine. I tantly, we want to tell stories that they are published, allowing only a also am the media contact for the others will share and remember. I promise: I get you. I respect you. handful of people (such as authors, ASBMB’s three scientic journals And that’s why I have to tell you that and annual meeting. Before coming press ocers and journalists) to see you’re disappointing me. Your refusal here, I was a press ocer at a univer- the material in the interim. One to promote research papers that can- sity on the science beat. Before that, often-cited aim is to facilitate thor- not be embargoed is undermining the I was a newspaper journalist. I’ve ough reporting of the research. But researchers you represent, devaluing pitched stories, and I’ve been pitched more and more publishers today post their work and diminishing your stories. profession. all accepted papers online imme- You probably can see, then, that diately. Most press ocers will still you and I have shared goals. We are Papers in press promote those papers to the media, committed to spreading the word even though the news cannot be about scientic discoveries that have ASBMB journals accept dozens of embargoed. But others will not. been hard fought and may one day CONTINUED ON PAGE 48

46 ASBMB TODAY AUGUST 2014 AUGUST 2014 ASBMB TODAY 47 CONTINUED FROM PAGE 47 The problem ers. ey’ve worked hard to gure out whatever it is that they’ve gured submissions every week, and each for press officers out. For all you know, they’ve worked acceptance letter asks researchers to I can think of several reasons you on that project for decades. Passing contact me if they’re going to work on their story is hardly the reward with their institutional press oce might not want to write about an they deserve for wanting the scientic on a release. I get queries every day unembargoed paper. Among the most community to know about their nd- from press ocers wondering about compelling: embargoes, and I explain to each the • Reading a paper, interviewing ings right away. ASBMB in-press policy: All accepted the authors, composing, checking • Don’t overestimate journal- papers are published online imme- facts, rewriting, editing and collect- ists. Trust me, most of them are not diately, putting them in the public ing media takes time. Embargoes give trolling journal websites to see which sphere and making them ineligible you that time. papers have just been accepted and for embargo. I tell them, usually in • You cannot promote every paper published online. ey’re lucky to these very words, “I know this makes your scientists churn out, so you pri- have you to do the digging. your job more dicult, but it’s good oritize. Embargoed papers, as noted • Don’t underestimate the impor- for science.” above, are relatively convenient. tance of your work. I don’t have to Some press ocers get it, and • The reporters you pitch to tell you how inuential press ocers sometimes I get a disappointing might ignore an unembargoed news are to the news cycle, but it is worth reply, like this one: “e press oce release. at means you’ll have fewer emphasizing. You’ve seen (and not will not consider a paper for a press media placements to report to your taken credit for) plenty of media release after it publishes.” researcher and, importantly, your reports that were conspicuously While I cannot speak for all boss. cribbed from your press releases. journals that immediately publish I concede all three points. Your job • Don’t become complacent. You’re accepted papers online (and there are is more intellectually challenging and a storyteller. at’s why you got into many of them), I can tell you that time consuming than most people, this business in the rst place. Stretch the ASBMB views its authors as its including scientists and journalists, yourself. You know that a great story primary customers. ose customers realize. You are burning calories like trumps timeliness any day and that are scientists at universities, federal crazy running around your campus, many times the real story isn’t even agencies and research institutes. In donning bunny suits to get into the the result of the study. Tell the story other words, those authors are the clean rooms and glad-handing politi- right, and nobody will care that the people that you, as a press ocer, cians visiting new research centers. paper isn’t under embargo. represent. Some (overworked or lazy) reporters I hope that you can acknowledge e scientic community clam- will disregard your unembargoed that I might have a point. All I ask is ors for the rapid dissemination of press release. Yes, writing about an that the next time a researcher with research results. Put simply, the hope unembargoed paper puts you at a a new unembargoed paper requests is to facilitate the quick production of disadvantage. a press release you actually read the more discoveries. e in-press policy But you can and, in many cases, paper and ask a few questions. You clearly was fashioned in response to should do it anyway. never know. ere might be a great that din. Publishers are meeting your story there. people’s needs. It’s the story that counts While researchers — both journal Best, authors and those scientists read- Here are my recommendations: Angela Hopp ing their papers — are the primary • Don’t operate under a false Editor, ASBMB Today beneciaries of the in-press policy, construct. e primary criterion for the public benets too. ey also can a press release is news value. at Angela Hopp ([email protected]) access these hot-o -the-virtual-presses a paper has been put in the public is editor of ASBMB Today. results right away. And that’s great, sphere does not diminish its news because, after all, they paid for feder- value. ally funded research with their taxes. • Don’t undermine your research-

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