April 2012 -OMICS DATA

VALID April 2012 -OMICS DATA

ALSO INSIDE THIS ISSUE: Special events at the annual meeting Poetry contest winners

American Society for Biochemistry and Molecular Biology

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AT0412_C2C1.indb 2 3/26/12 3:17 PM contents APRIL 2012 On the cover: ASBMB Today science writer Rajendrani news Mukhopadhyay looks 3 President’s message into how the mountains Evolution and molecular Lego of -omics data being produced should and 5 News from the hill could be validated. 14 Hill Day 2012 6 the Capitol hill cohort 8 FaSeb update 9 member update headed to San Diego for the annual 10 annual awards meeting? Find out 10 Herbert Tabor/JBC Lectureship winner about special events, 11 William C. Rose Award winner read the winning 12 Earl and Thressa Stadtman Scholar Award winner poetry contest entries and check out our 13 Ruth Kirschstein Diversity in Science Award winner list of recommended mobile apps to make feature your trip go smoothly. 14 Valid -omics 20 – 25 How should massive quantities of -omics data be validated? annual meeting 20 Special events and more 20 Fun run, mixers and programs 22 Science in stanzas: poetry contest results When Dennis Vance asked 24 Mobile apps and social media notes his students if they knew about Konrad Bloch, left, essay he wasn’t encouraged by 26 tribute to midlevel scientists their responses. 27 departments 27 lipid News Are we doing a good job of teaching the groundbreaking research of our predecessors? Sonia C. Flores offers step-by-step advice 28 Journal News for those new to the 28 JBC: Worm protein provides insight NIh grant-application into aging and neurodegeneration process. 30 28 JLR: How the only FDA-approved drug for primary biliary cirrhosis works in the liver 29 MCP: Serum antibodies as biomarkers 30 minority affairs Navigating the NIH grant-application process 32 education onlineex clusiv Indications of a bright future through science We’re pleased to announce that science writer 34 Open Channels Rajendrani Mukhopadhyay now has a blog. 34 Letter to the president Follow her quips and queries at www.asbmb.org/asbmbtoday. 34 Response to ASBMB premed curriculum recommendations

April 2012 ASBMB Today 1

AT0412_C2C1.indb 1 3/26/12 3:17 PM onlineex clusiv A monthly publication of www.asbmb.org/asbmbtoday The American Society for Biochemistry and Molecular Biology

Ofﬁ cers Suzanne R. Pfeffer President Jeremy M. Berg President-Elect research Mark A. Lemmon Secretary Merle S. Olson Treasurer Spotlight Toni M. Antalis Treasurer-Elect Council members read two “research spotlight” Karen N. Allen Ruma V. Banerjee interviews with elizabeth Benjamin F. Cravatt Michael A. Marletta ntantie (left), a pharmacology David Sabatini John D. Scott Melissa Starovasnik Wesley I. Sundquist graduate student at the medi- Jonathan S. Weissman cal College of Wisconsin, and ex-Ofﬁ cio members with Casonyta matese Johnson Russell DeBose-Boyd hongtao Yu (right), an associate professor Co-chairs, 2012 Annual Meeting Program Committee of biology at georgia state uni- Peter J. Kennelly Chair, Education and Professional Development versity, by asBmB’s education Committee Joan W. Conaway and professional development Chair, Meetings Committee manager, Weiyi zhao. Terri Kinzy Chair, Membership Committee Squire J. Booker Chair, Minority Affairs Committee Bettie Sue Masters Chair, Public Affairs Advisory Committee Charles Brenner discovery through writing Chair, Publications Committee Want to know more about the scientists who won the Martha J. Fedor, Editor-in-chief, JBC ASBMB poetry contest being held in conjunction with herbert Tabor, Co-editor, JBC Ralph A. Bradshaw Experimental Biology 2012? Make sure to visit A. L. Burlingame Co-editors, MCP our website to read their bios. You’ll also fi nd bios by the Edward A. Dennis contest judges— some serious and some not so much. Joseph L. Witztum Co-editors, JLR ASBMB Today editorial advisory board Alex Toker (Chair) Mike Bradley Craig E. Cameron A. Stephen Dahms Alex C. Drohat ASBMB Today is Ben Ellington Irwin Fridovich Richard W. hanson Gerald hart Peter Kennelly Carol C. Shoulders now on Pinterest! aSbmb today Join us at http://pinterest.com/asbmbtoday/. Angela hopp Editor We’ve pinned all of our magazine covers [email protected] from the past 10 years. If you let us know Rajendrani Mukhopadhyay Sr. Science Writer / Editor which ones are your favorites, it’ll help [email protected] us plan future covers. Erin Salb Production Coordinator [email protected] Nancy J. Rodnan Director of Publications [email protected] Barbara Gordon Executive Director [email protected]

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April 2012

AT0412_C2C1.indb 2 3/26/12 3:17 PM president’smessage Evolution and molecular Lego BY SUZANNE PFEFFER

ot far from the traffic and cacophony of downtown tion. I often have neglected to consider evolution when N Bangalore is a quiet, secluded compound that trying to understand the molecular basis of a given cel- houses India’s National Centre for Biological Sciences of lular process. Evolution adds an important dimension. the Tata Institute of Fundamental Research. Now in its “Bringing together molecular cell biologists, immunol- 20th year, this center of research excellence is powered ogists and evolutionary biologists who appeared ready by scientists studying biochemistry, biophysics and bio- to candidly discuss their favorite cellular processes and informatics; cellular organization and signaling; ecology structures and debate the origins of cellular compart- and evolution; genetics and development; neurobiol- ments and cellular immunity, in the context of new ideas ogy; and theory and simulation of biological systems. about genes and their capacity for evolution, was a risky I had the pleasure of visiting the NCBS in February to experiment for us as organizers of this conference,” said attend an international workshop and research confer- Mayor. “The quality of discussion and the fount of new ence titled “The Evolutionary Origins of Compartmental- ideas generated suggest that this experiment was wildly ized Cells.” India’s International Centre for Theoretical successful. This augers well for a bright future for the Sciences provided funding for the meeting as part of its exciting and emerging field of evolutionary cell biology.” mission to nucleate new areas of research by bringing Thattai echoed Mayor’s sentiments, saying, “One of together scientists from diverse fields. the great things about studying the evolution of cells The conference was organized by Frances Brod- is that no topic is off limits. Though ours was a diverse sky from the University of California at San Francisco, meeting by any standard, with topics ranging from together with Satyajit (Jitu) Mayor and Mukund Thattai organelle biology to phylogenetics to ancient viruses, from NCBS. Their goal was to bring together evolution- I found fascinating and relevant ideas to take away ary biologists, cell biologists and immunologists to try from every talk.” to synthesize what these disciplines can teach us about Brodsky added, “Molecular cell biologists inter- the origins of the first eukaryotic cell and the origin of ested in the evolutionary origins of pathways we study the human immune system. The conference taught me can learn a lot from immunologists who have refined an important lesson: Evolution of a biochemical process techniques to extract information from the co-evolution can teach us a great deal about how it operates— of host–pathogen interaction pathways, which are the it can help determine which features are fundamental most rapidly evolving in biology.” and which represent cellular or organismal specializa- I was invited to the conference because I share a common experience with one of the organizers, Brodsky. A manuscript referee once told each of us (independently) that the human proteins that we were describing couldn’t be relevant because that gene product is not present in mice (even though it was present in all other vertebrates). Some take the even more extreme The conference was organized by Frances Brodsky of the University of California at San Francisco, Satyajit (Jitu) Mayor, center, and Mukund Thattai from India’s National Centre for view that if we understand Biological Sciences. a process in yeast it is not

April 2012 ASBMB Today 3

AT0412_C2C1.indb 3 3/26/12 3:17 PM ﬁpresident’s rsts ond messcontinued age continued worth studying in humans because we already under- energize us, stimulate new ideas and catalyze the dis- stand the fundamentals. covery of novel connections between diverse proteins, This cannot be correct: We need to understand the pathways or systems. regulation of human pathways that will differ in different This month, ASBMB holds its annual meeting in San cell types, tissues and/or developmental stages. Many Diego, and we are also sponsoring a number of mem- diseases can be attributed to proteins that are found ber-initiated, smaller meetings on a variety of topics. We only in humans and for which the genes represent encourage you to help identify cutting-edge, interdisci- duplication and diversifi cation to yield traits needed plinary topics for consideration for ASBMB-sponsored for our complex physiology. Thus, the study of human special symposia and/or annual meeting themes for next cells and tissues is important; the study of nonhuman year and beyond. In the meantime, I look forward to see- organisms and pathogens is also important. When we ing you in San Diego! see convergent evolution provide the same solution to a complex problem, we have a better understanding of ASBMB President Suzanne Pfeffer (pfeffer@ its importance. stanford.edu) is the Emma Pfeiffer Merner professor of medical sciences and a biochemistry professor Molecular Lego at the Stanford University School of Medicine. As we obtain more and more protein structures, we see that certain folds are used to achieve distantly related but likely functionally similar processes. Sometimes structure conservation is achieved by gene duplication, 2012 ASBMB but other times convergent evolution appears to come SPECIAL SYMPOSIA to a common solution. Structural biologists surely know more of this than the rest of us (and I implore them NEW THIS YEAR: here to please write a review or send one to me); all of Minority travel awards are available for each symposium. See the website for us should learn more about this. When we fi nd proteins deadlines and details about this and other of unknown function, structurally related proteins may opportunities. provide us with important clues to how that protein www.asbmb.org/specialsymposia works. A wonderful example is the structure of certain Trypsin-Like Proteases: Structure, nuclear pore complex proteins that resemble elements Function and Regulation of clathrin transport vesicle coats: They are made up June 7 – 10, Tahoe City, Calif. of an alpha solenoid connected to a beta propeller to form a fl exible, macromolecular assembly. Transport Mitochondria: Energy, Signals and Homeostasis vesicle tethering factors share this feature; perhaps June 27 – June 29, East Lansing, Mich. this is trying to tell us that transport vesicle coats once performed a tethering role. Frontiers in Lipid Biology Sept. 4 – 9, Banff, Alberta, Canada The conference was fl anked by tutorial lectures by many of the speakers to provide the background Transcriptional Regulation: Chromatin information needed for students (and faculty members) and RNA Polymerase II Oct. 4 – 8, Snowbird, Utah from diverse areas to be able to appreciate the topic. This made it possible to include a truly interdisciplinary Post-Translational Modiﬁ cations: set of speakers and topics. In times of tight research Detection and Physiological Role Oct. 11 – 14, Tahoe City, Calif. funding, it may be more important than ever before to encourage scientists to organize and attend such combination workshop/conferences. A great way to ini- tiate valuable collaborations is to bring people together and provide them with lots of time to interact with one another and to learn what each other is thinking about. Collaboration will continue to be more important when funds are tight, and the best collaborations team scientists from different disciplines who can bring to the table distinct approaches and tools. Meetings can

4 ASBMB Today April 2012

AT0412_C2C1.indb 4 3/26/12 3:17 PM news from the hill Hill Day 2012 BY JULIE MCCLURE

n March 27, 19 students and post- Odocs joined the American Society for Biochemistry and Molecular Biology Public Affairs Advisory Committee in Washington, D.C., to meet with more than 60 congressional offi ces in 2011 (1). This funding has an economic effect that and advocate for basic research funding and biomed- reaches far beyond the individual labs it goes to, creating ical-related legislation. This year represents the fourth more than 15,000 new jobs and producing $182 million annual ASBMB Student/Postdoc Hill Day, and every year in new business activity in Kansas (2). The positive eco- we refi ne our message to Congress. Here are some of nomic effect of the research enterprise is a message that the issues the Hill Day participants addressed this year. carries signifi cant weight on both sides of the aisle.

Strong, sustained funding for Support for legislation that benefi ts the National Institutes of health biomedical researchers Since 2008, the National Institutes of Health’s funding While NIH funding is always the main topic of discussion levels have increased— but at a rate lower than that of on Hill Day, there are several pieces of legislation that infl ation. As a result, the purchasing power of the NIH have been put forward in the 112th Congress that would has dropped steadily. Feast-or-famine funding at the NIH have positive effects on the biomedical research com- is highly disruptive to training, careers and long-range munity. In both the U.S. House and Senate, there are research projects. Sustained funding for the NIH is critical several bills that propose tax credits for costs associated if researchers hope to continue their work. This year, the with biomedical or life-science research. The Stem Cell Hill Day participants brought a message to Congress that Research Advancement Act would allow the use of fed- addressed this. ASBMB is calling for $32 billion in fund- eral funding on research using human embryonic stem ing for the NIH for FY13 with a move to reach $35 billion cells. The Stopping American-Trained Ph.D.s from Leav- by FY15. This plan will provide the NIH and biomedical ing Our Economy Act, otherwise known as the STAPLE researchers with predictable NIH funding to maximize our Act, proposes immigration reforms that would allow nation’s long-term return on its investment in research. students who earn science, technology, engineering or math Ph.D.s to continue to work in America. The Hill Day The positive economic impact of an participants highlighted bills such as these in their meet- investment in biomedical research ings to try to garner further support for them. All you have to do is turn on the news today and you’ll The visits to the Hill are part of an ongoing education quickly see that the economy is on everyone’s mind. strategy directed by ASBMB’s PAAC. Visit our website or Unemployment remains high, and the country is won- contact our offi ces if you would like to learn how you can dering how we will turn this economic downturn around. be a part of these efforts. During Hill Day, ASBMB members showed their elected offi cials how investing in biomedical research not only is Julie McClure ([email protected]) is the an investment in the overall health of our nation but also science policy fellow at ASBMB. an investment that results in millions of jobs. It’s easy to show that areas such as Boston, San Francisco and North Carolina’s Research Triangle are reaping the benefi ts of research funding, but many members of Congress are surprised to see the signifi cant economic impact referenCes research has throughout the country. Take Kansas, for 1. Budget data obtained from the NIH Research Portfolio website: http://report.nih.gov/index.aspx. 2. Statics based on 2007 data from “In Your Own Backyard: How NIH Funding Helps Your State’s instance. The state received $136.4 million from the NIH Economy” (2008). Families USA: Washington, D.C.

April 2012 ASBMB Today 5

AT0412_C2C1.indb 5 3/26/12 3:17 PM asbmbnews The Capitol Hill cohort

Nineteen young ASBMB members, along March to advocate for adequate and with a handful of Public Affairs Advisory sustained federal funding for biomedical Committee members and the main office’s research. Here are snapshots of the young policy staffers, took to Capitol Hill in late participants and their research interests.

Valerie O’Shea Kaustubh Bhinge University of California, Berkeley, postdoc University of Louisiana at Monroe, Structure and function of molecular Ph.D. candidate machines involved in bacterial DNA Role of glucosylceramide synthase replication initiation in the regulation of breast cancer metastasis and cell-cycle regulation

Robert Linder Cherie Ramirez University of Southern California, Harvard University, Ph.D. candidate Ph.D. candidate Ensuring that our technology for Mechanisms through which the editing the genetic code of living proteasome is regulated during the cells— zinc finger nucleases— adaptive response to oxidative stress has the lowest risk of unwanted side effects possible so that it can be used most effectively for curing human disease

Kristy Lamb Matthew Shirley Yale University, Ph.D. candidate Johns Hopkins University School How subtle variation in DNA repair of Medicine, Ph.D. candidate genes changes the efficiency of Identifying genomic causes of DNA repair and how that affects an childhood neurological diseases, individual’s risk of developing cancer or such as autism, using human his or her response to chemotherapy genome resequencing and DNA microarray technology

Chris Carmean Chris Pickett University of Chicago, Ph.D. candidate Washington University in St. Louis, Regulation and physiological postdoc significance of brown adipose tissue carbohydrate metabolism during Degenerative changes that cause fasting followed by refeeding age-related reproductive complications

6 ASBMB Today April 2012

AT0412_C2C1.indb 6 3/26/12 3:17 PM asbmbnews Melissa Hargreaves George Jules University of Montana, graduate student Meharry Medical College, Characterizing ribosome biogenesis Ph.D. candidate from an unusual ribosomal RNA How benzo[a]pyrene exposure operon in the Lyme disease in utero alters the cardiovascular bacterium Borrelia burgdorferi system to contribute to cardiovascular disorders in later life

Anne McCabe Rebecca Johnson Princeton University, graduate student University of Texas Health Science Center, Ph.D. candidate Outer membrane biogenesis in E. coli, focusing on members of Cancer biology the BAM complex responsible for assembling Beta-barrel proteins within the outer membrane

Joshua Roxby CLinton Copeland University of New Mexico, Norfolk State University, postdoc Ph.D. candidate Reproductive biology Characterizing a novel PARP inhibitor to be delivered to ovarian cancer cells with Cisplatin using silica-supported lipid nanoparticles

Christine LeRoy Abigail Schindler University of Washington, New York Medical College, Ph.D. candidate Ph.D. candidate Biochemical and molecular basis Human DNA replication enzyme of stress-induced depression and DNA polymerase delta, including potentiation of cocaine reward its implications in the DNA damage response and its roles in the maintenance of genomic integrity

Melinda Hough John LaCava University of Washington, postdoc Rockefeller University, postdoc Understanding the molecular Specializing in applied scientific mechanisms of bacterial cell death research on molecular interaction caused by antibiotic treatment in order dynamics to provide fundamental insights and future avenues for drug development

Jonathan Proto University of Pittsburgh Become a fellow School of Medicine, Ph.D. candidate ASBMB is now accepting applications for its 2012 – 2013 Nuclear factor Kappa B signaling in the regulation of muscle stem Science Policy Fellowship program. cell phenotype and the possible Visit www.asbmb.org for more information. implications this may have for the The deadline is April 15. aging process

April 2012 ASBMB Today 7

AT0412_C2C1.indb 7 3/26/12 3:17 PM fasebupdate Recommendations for engaging basic scientists in translational research BY Anne M. Deschamps

he Federation of American Societies for Experimen- Conference participants were asked to identify ways Ttal Biology released a report last month describ- to address these challenges, with a focus on helping ing how research institutions, funding organizations, basic scientists acquire translational research training, professional societies and scientific publishers can facilitating collaborations, receiving recognition and facilitate the participation of basic scientists in transla- rewards, and defining the role of funding organizations. tional research. The report, “Engaging Basic Scientists These discussions provided FASEB’s Translational in Translational Research: Identifying Opportunities, Research Steering Committee with the material to Overcoming Obstacles,” is based on the proceedings of shape the set of realistic recommendations below. a two-day symposium held in March 2011 that brought Funders should together more than 150 basic, clinical and translational • continue to support basic research to ensure a deep scientists, scientific journal editors and leaders from and broad reservoir of new knowledge upon which private and public research organizations. The report translational and clinical science can grow, addresses the benefits of conducting translational • provide specific funding for investigator-initiated translational research and research, challenges basic scientists face in developing • ensure that grant application reviewers have appropriate translational research programs and practical recom- expertise to review translational research projects. mendations for overcoming those challenges. Research institutions should Basic scientists are the foundation of the biomedical • provide didactic and experiential learning opportunities research enterprise. Their work is key to understand- that place basic research in the context of ing fundamental biological processes and mechanisms pathophysiology and pathobiology, of disease pathogenesis, and it has been critical to • create opportunities for interdisciplinary collaboration: preventing, diagnosing and treating diseases and condi- • connect basic scientists with the infrastructure, tions that afflict millions of people. FASEB’s symposium equipment, and technical and administrative support featured a number of basic investigators who benefit- necessary to move their discoveries from the bench to the bedside and ted from pursuing the translational applications of their • revise tenure and promotion polices to recognize work. They described how they learned new methods, interdisciplinary, team-based translational work. expanded their insights into biological mechanisms of Scientific publishers should disease and even improved their publication rates. • ensure that the roles of individual authors are clearly In spite of these benefits, numerous factors can articulated in publications and impede or prevent basic researchers from embarking on • encourage editors to identify and highlight the translational research projects. The physical and cultural contributions that basic research findings could make separation of basic and clinical departments limits to medicine and public health. opportunities to interact and collaborate, basic scien- Professional scientific societies should tists may not have access to the research resources, • spark interest in translational research by raising its funding and support systems needed to conduct trans- profile in featured symposia, workshops and sessions at professional meetings; lational science, and unfamiliar and complex regulatory • provide resources and opportunities to facilitate issues can deter them from moving a project forward. interactions among basic and clinical researchers; In addition, tenure and promotion committees may not • provide awards for exceptional contributions to team, accord the same value to participation in translational interdisciplinary and translational science and research, which tends to be goal-directed, interdisciplin- • advocate for policies and programs that facilitate ary and team-based, as they do to hypothesis-driven participation of basic scientists in translational research. basic science conducted by individual investigators. continued on page 9

8 ASBMB Today April 2012

AT0412_C2C1.indb 8 3/26/12 3:17 PM asbmb member update

BERMAN HONIG LEMMON LINDQUIST SMERDON

berman, honig, which are among the most widely used European Molecular Biology Organiza- lemmon lauded programs in structural biology.” The soci- tion late last year. Lindquist, who is also ety also emphasized the value of Honig’s a Howard Hughes Medical Institute by Protein Society discoveries related to cell-cell adhesion investigator, will now have a lifetime Helen M. Berman of Rutgers University and sequence-dependent protein-DNA membership. Lindquist’s work on protein won the Carl Brändén Award, given to recognition. Mark Lemmon of the Uni- folding was featured in the Feb. 15 issue an outstanding protein scientist who has versity of Pennsylvania Perelman School of Nature and the Feb. 16 issue of New made exceptional contributions in the of Medicine won the Dorothy Crowfoot Scientist. areas of education and/or service. In a Hodgkin Award for his signifi cant contribu- statement, the society said Berman was tions to the fi eld of signal transduction and Smerdon wins recognized for her work toward enabling transmembrane signaling mechanisms top faculty award a freely available, worldwide archive of of receptor tyrosine kinases. The society Michael J. Smerdon of the School of 3-D structural information. “Dr. Berman’s said: “Crystallographic, biochemical Molecular Biosciences at Washington passion for making structural data acces- and genetic studies from his laboratory State University has won the 2012 sible and understandable by a broad have provided sophisticated mechanistic Eminent Faculty Award, the highest community has driven the development understanding of EGFR cell signaling. His honor the university offers, for career- of the Protein Data Bank into a vital and discoveries of the mechanisms for the long excellence. Smerdon, one of the accessible international resource for epidermal growth factor receptor family fi rst researchers to analyze how repair biology. Berman in the early 1970s was a offer new venues for developing novel is infl uenced by the way DNA is pack- champion of the open access of scientifi c therapeutic approaches targeting cancer aged and to recognize that the repair information; albeit obvious today, the and other human diseases.” response to genetic signals is turned on concept at that time of open access was and off by environmental conditions, has truly visionary.” Barry Honig of Columbia served as a Journal of Biological Chem- University won the Christian B. Anfi nsen lindquist earns istry editorial board member and is a Award for signifi cant technical achieve- lifelong embO honor fellow of the American Association for the ments. Honig was singled out “for his Susan Lindquist of the Whitehead Institute Advancement of Science. In 2006, he was contributions to our understanding of the at the Massachusetts Institute of Technol- recognized as among the top 5 percent of electrostatic properties of proteins and ogy was one of three U.S. scientists extramural NIH grant awardees over the the development of DelPhi and GRASP, who became associate members of the past 25 years.

continued from page 8 of their work and to create an environment that provides them with opportunities to translate their discoveries into Individual researchers should human health applications. The conference proceedings • learn to defi ne a health need with the same precision and the complete set of recommendations are available as a basic science hypothesis, here: http://www.faseb.org/Policy-and-Government- • seek mentors/collaborators from different disciplines and Affairs/Publications.aspx. • negotiate concurrence with departments as to how translational research will be evaluated in the tenure and promotions process. Anne M. Deschamps ([email protected]) FASEB’s goal in developing these recommendations is is a science policy analyst in the Offi ce of Public not to turn basic scientists into clinical trialists. Rather, it is Affairs at FASEB. to encourage them to consider the translational potential

April 2012 ASBMB Today 9

AT0412_C2C1.indb 9 3/26/12 3:18 PM asbmbnews TABOR/JBC LECTURESHIP Kornfeld’s contributions recognized for their ‘rigor and scientiﬁ c breadth’ BY GEOFF hUNT

he American Society her that day. “His incredibly tfor Biochemistry and signifi cant contributions to Molecular Biology has named glycobiology and cell biology, Stuart Kornfeld, professor elegantly simple scientifi c of medicine in the School of approach, and ability to ask Medicine at Washington Uni- the most important questions versity in St. Louis, the win- and solve complex problems ner of the society’s Herbert make this amazingly humble Tabor/Journal of Biological man an extraordinary scientist Chemistry Lectureship. and human being.” Kornfeld received the University of Chicago pro- award for his seminal fessor Ben Glick agreed. “Dr. research in the fi eld of Kornfeld’s contributions are glycobiology, in particular spectacular in their combi- his work describing multiple nation of rigor and scientifi c novel pathways involved in breadth.” oligosaccharide biosynthesis, Kornfeld was an under- processing and maturation. graduate at Dartmouth Col- These actions subsequently lege and earned his M.D. from were shown to be critical in the Washington University mediating proper folding and in St. Louis medical school, transport of major cellular where, save for a brief stint at proteins, including those the NIH from 1963 to 1965, that regulate activity of the lysosome, a critical organelle he has remained his entire career. He ran the school’s involved in the degradation of macromolecules. Kornfeld hematology division for more than 30 years. also showed that disruptions in these processes could Kornfeld will receive his award during the Experimen- cause a range of metabolic diseases that have severe tal Biology 2012 conference in San Diego, where he effects on organ systems. will deliver the opening lecture of the conference. The The award has special meaning for Kornfeld. “Herb presentation will take place at 6 p.m. April 21 in the San Tabor has been one of my heroes since I fi rst met him at Diego Convention Center. the National Institutes of Health in the 1960s,” he said. “I am very honored to be selected.” Karen Colley, professor at the University of Illinois- about the award Chicago, said she remembered “feeling very special The herbert Tabor/Journal of Biological Chemistry when Stuart, at the beginning of a seminar years ago, Lectureship recognizes outstanding lifetime scientifi c achievements and was established by the ASBMB to announced to the audience that, by virtue of having acknowledge the many contributions of herbert Tabor worked for Jacques Baenziger (his fi rst graduate student), to the society and the journal, of which he served as I was therefore his granddaughter in science!” She was editor for nearly 40 years and now serves as co-editor. quick to reciprocate the pride Kornfeld expressed for

10 ASBMB Today April 2012

AT0412_C2C1.indb 10 3/26/12 3:18 PM asbmbnews WILLIAM C. ROSE AWARD Marqusee lauded for protein-folding research and ‘encouragement of the next generation’ of scientists BY GEOFF hUNT

he American Society from the physical chemistry tfor Biochemistry and of macromolecules to the Molecular Biology has named design of therapeutics that Susan Marqusee, professor prevent the aggregation of molecular and cell biology of proteins which lead to at the University of Califor- common diseases such as nia, Berkeley, and director of Alzheimer’s,” they wrote in Berkeley’s California Institute their nominating letter. for Quantitative Biosciences, Marqusee’s mentorship the winner of the society’s efforts also are recognized William C. Rose Award. by the Rose Award. Her “I’m honored to receive colleague Jane Clarke from an award that recognizes the University of Cambridge the sum total of what I love hailed Marqusee as “an about my job— science, all-too-rare example of an mentorship and training,” academic who is not simply a said Marqusee. “For me, it’s stellar scientist but someone the melding of all three areas who explicitly factors into her that gives me the greatest way of doing science dedica- satisfaction.” tion to encouragement of the Marqusee received the next generation. Her students award in recognition of her simply adore her.” extensive thermodynamic Marqusee will get her and kinetic studies using award and deliver her lecture hydrogen-exchange, nuclear magnetic resonance, and at 9:05 a.m. April 24 at the Experimental Biology 2012 single-molecule methods to study protein structure and meeting in the San Diego Convention Center. behavior at increasingly sharper resolution. Accord- ing to Walter Englander, professor at the University of Pennsylvania, “this work convincingly revealed that about the award proteins are composed of cooperative nativelike foldon The William C. Rose Award recognizes outstanding units and demonstrated their key role in protein-folding contributions to biochemical and molecular biologi- pathways.” cal research and a demonstrated commitment to Professors Carlos Bustamante and Jennifer Doudna the training of younger scientists as epitomized by of the University of California, Berkeley, nominated the late Rose, an authority on protein nutrition and Marqusee for the award. “The fundamental nature of Dr. former president of the ASBMB. The award consists of a plaque, $3,000 and transportation to the 2012 Marqusee’s work has had, and will continue to have, ASBMB annual meeting to present a lecture. signifi cant impact on many areas of research, ranging

April 2012 ASBMB Today 11

AT0412_C2C1.indb 11 3/26/12 3:18 PM asbmbﬁ rsts newsond continued continued EARL AND THRESSA STADTMAN SCHOLAR AWARD Sabatini honored for ‘providing critical insights into the linkages between energy, nutrient metabolism and cancer’ BY GEOFF hUNT

he American Society for earned praise for his techno- tBiochemistry and Molecu- logical inventions, including the lar Biology has named David reverse transfection microarray, Sabatini, associate professor a rapid, high-scale through- of biology at the Massachu- put technique in which cells setts Institute of Technology expressing defi ned cDNAs are and a Howard Hughes Medical screened for select phenotypes, Institute investigator, the win- thereby enabling investigation ner of the society’s inaugural into the effects of varying gene Earl and Thressa Stadtman expression levels on a cellular Scholar Award. rather than population level. Sabatini received the This technology also allows for award for his work identifying simultaneous screening of the the mTOR pathway, a major effi cacy of multiple small-mole- regulator of mammalian cell cule compounds that serve as growth and a central compo- potential drug candidates. nent of pathways relating to “I am delighted to receive metabolism and aging. Susan this honor from my colleagues Lindquist, a professor at MIT, and am humbled to receive an praised Sabatini’s work on award named for pioneering mTOR for “providing criti- biochemists whose work has cal insights into the linkages infl uenced all of us who pretend between energy, nutrient to be one,” said Sabatini. metabolism and cancer.” Sabatini will receive his award The work done by Sabatini’s lab has led to the devel- during the Experimental Biology 2012 conference in San opment of several drugs aimed at treating cancer. His lab Diego, where he will deliver an award lecture. The presenta- also recently has demonstrated the ability of diet to affect tion will take place at 8:30 a.m. April 23 in the San Diego aging and cell growth. Convention Center. Solomon Snyder from Johns Hopkins University was not bashful in his praise for his former graduate student. about the award “Virtually all of the major breakthroughs relating to signal- The Earl and Thressa Stadtman Scholar Award ing pathways whereby growth factors and nutrient amino was established by their friends and colleagues to acids regulate protein translation can be attributed to one preserve their legacies as scientists and mentors. It is individual: David Sabatini,” Snyder said. awarded to a scientist with 10 or fewer years of post- Upon completing his M.D./Ph.D. at Johns Hopkins, postdoctoral experience, including medical residency Sabatini was invited to become a fellow at the prestigious and fellowship. The award is given every other year, Whitehead Institute in 1997. He was elevated to full mem- alternating with the Earl and Thressa Stadtman ber in 2002. Sabatini also began a professorship in the Distinguished Scientist Award. The award consists of a plaque, a $10,000 cash award and travel expenses department of biology at MIT in 2005. for the ASBMB annual meeting to present a lecture. In addition to his experimental insights, Sabatini has

12 ASBMB Today April 2012

AT0412_C2C1.indb 12 3/26/12 3:18 PM asbmbﬁ rsts newsond continued continued RUTH KIRSCHSTEIN DIVERSITY IN SCIENCE AWARD ‘No one has been more dedicated to increasing the pipeline of minority scholars than Lovell Jones’ BY GEOFF hUNT

he American Society for Biochemistry and tMolecular Biology has named Lovell Jones the “Perception is reality winner of the society’s Ruth Kirschstein Diversity to those who perceive in Science Award. Jones is a professor at both the it… Until you address University of Texas MD Anderson Cancer Center the perception, you will and the University of Houston as well as director never be able to truly of the joint Center for Health Equity & Evaluation address the reality. In Research. setting up the minor- Throughout his career, Jones has focused on ity training programs, minority health issues. He was a co-founder of the Ruth took both aspects Intercultural Cancer Council, the nation’s larg- into account. It is truly est multicultural health policy group focused on an honor receiving this minorities, the medically underserved and cancer; award in her name.” chaired the fi rst Biennial Symposium on Minorities LOVELL JONES and Cancer in 1987; and was among the leaders who worked with members of Congress to desig- nate the third week of every April National Minority Cancer focusing primarily on the role of estrogen and environ- Awareness Week. mental estrogenic agents in tumor induction in hormon- Thomas Landefeld, professor at California State ally responsive tissues. University–Dominguez Hills, praised Jones for being Jones will receive his award during the Experimen- “totally devoted to diversity issues in the scientifi c tal Biology 2012 conference in San Diego, where he community, with a major emphasis on both addressing will deliver an award lecture. The presentation will take the underrepresentation of minorities at all levels in place at 2:55 p.m. April 23 in the San Diego Conven- academia, industry and government, as well as the tion Center. overwhelming issue of health disparities in our nation.” Jones also has shown great dedication to mentorship Geoff Hunt ([email protected]) is ASBMB’s public of underrepresented groups. In supporting his nomina- outreach coordinator. tion for the award, Marian Johnson-Thompson, professor emerita of the University of the District of Columbia, cited his “attention to promoting diversity in training programs, which has led to the next generation of health- disparities researchers and policy leaders.” Judith Kaur, about the award from the Mayo Clinic, agreed: “No one has been more The Ruth Kirschstein Diversity in Science Award was dedicated to increasing the pipeline of minority scholars established to honor an outstanding scientist who has than Lovell Jones.” shown a strong commitment to the encouragement of In addition to his efforts involving minority health underrepresented minorities to enter the scientifi c enter- disparities, Jones is also a pre-eminent scientist. He prise and/or to the effective mentorship of those within it. The award consists of a plaque, a cash prize of $3,000 holds both M.S. and Ph.D. degrees in zoology from the and transportation expenses to present a lecture at the University of California, Berkeley, and has worked in the ASBMB annual meeting. department of biochemistry at MD Anderson since 1980,

April 2012 ASBMB Today 13

AT0412_C2C1.indb 13 3/26/12 3:18 PM featurestory VALID -OMICS With the massive quantities of -omics data being produced today, how should they be validated? BY RAJENDRANI MUKhOPADhYAY

14 ASBMB Today April 2012

AT0412_C2C1.indb 14 3/26/12 3:18 PM Genomics, transcriptomics, proteomics — the list of fi elds with “-omics” as the suffi x has ballooned, and so has the excitement and anticipation of what these fi elds can deliver. When so many biomolecules are tracked at once, scientists can get more detailed and complete pictures of the complex connections between different molecular pathways, cellular and tissue conditions, and pathologies. With the more detailed pictures, researchers can deepen our understanding of biology and even develop novel clinical diagnostic tests or therapeutic treatments to improve public health.

But in the excitement over the promise of -omics different beast. “For -omics research, the complexity is technologies, “the issue of validation, an important so immense that we cannot really afford to just go for one, has been a bit neglected,” says James P. Evans at discovery without validation,” says Ioannidis. “Valida- the University of North Carolina at Chapel Hill. He and tion should be built into the process of discovery.” other researchers, whose expertise range from funda- Hypothesis-generated research — when one or mental research to clinical epidemiology, are worried two variables are tested against one or two others — that if data validation is not properly done, discoveries tends to produce a few results, which are relatively from -omics endeavors will be pointless. easy to validate with simple statistical tests. But The notion of validation is not anything new. -omics data sets contain thousands, even millions, “The process of replication is a hallmark of sci- of molecules. Because of the sheer quantity of data, ence,” says John Ioannidis of Stanford University. Keith Baggerly at the University of Texas MD Anderson Scientists “don’t just blindly trust results, because Cancer Center says, “I no longer believe that we have trust belongs to dogma.” good intuition about what makes sense.” Because of But experts say that validation of -omics data is a this lack of intuition to grasp what large data sets are

April 2012 ASBMB Today 15

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revealing, Baggerly says these data sets need to be ferent method on the same sample set gives them independently verified and checked in multiple ways. the same answer. The need for validation is growing increasingly Next are the bricks of independent repeatability urgent, especially when a significant number of -omics and replication. Researchers not connected with studies are targeted for medical applications. “There is the original group must see if they can carry out plenty of research that focuses on the initial discov- the same experiments and get the same answers. ery phase but not enough research on replication, If the analysis has clinical implications, it should also validation and translation,” argues Muin Khoury at the be carried out in larger cohorts to see if the same Centers for Disease Control and Prevention, who with results emerge. Ioannidis recently made some recommendations about The next brick of validation is interpretation, the validation of -omics data for clinical studies (1). and this one “is the toughest of all,” says Ioan- Experts all brought up the two cautionary tales nidis. “Even when everything has been repeatable, of what can go wrong when -omics data are not reproducible and replicable, there is some room for scrutinized: Correlogic’s OvaCheck test of 2004 and differences in opinion.” Ioannidis says that, while he Anil Potti and Joseph Nevins’ clinical trials at Duke believes in the freedom of researchers to interpret University (see sidebar). The Institute of Medicine has data as they see fit, some standards need to be set reviewed how -omics data should be validated for in how to interpret data for different fields. clinical trials (see http://iom.edu/Activities/Research/ The final brick is asking whether the newly OmicsBasedTests.aspx). discovered information helps us. “Even if you know what a variant means, and even if it is one you can act on, does acting on it actually improve public health?” asks Adam Felsenfeld at the National The need for validation is growing Human Genome Research Institute. “It is a huge issue that has to be tackled not just by the clinical increasingly urgent, especially community but by health-care economists” and when a significant number of others. He gives the example of the prostate cancer screening test, whose true clinical utility in reducing -omics studies are targeted for the burden of disease has been debated. He says that kind of consideration for clinical utility should medical applications. be built into -omics research as early as possible.

No one-size-fits-all solution Much of the emphasis has been on validating In discussing validation, it’s important to appreci- -omics data relevant for clinical applications, because ate that the different -omics fields can’t be lumped patient safety is of utmost importance. But Ruedi together. The information gleaned from these fields Aebersold at the Swiss Federal Institute of Technology “encompasses so many different kinds of data. Each in Zurich points out that validation also has significant one of them has its own technical challenges with repercussions in fundamental research. “True, patients respect to validation,” says Ralph Bradshaw at the aren’t hurt if someone misassigns a protein in a yeast University of California at San Francisco and co-editor project,” he says. “But it’s still an enormous waste of of Molecular & Cellular Proteomics with Alma Burlin- resources and effort. It’s generally bad for science if game at the same institution. (MCP is published by the data are poorly reproducible or misassigned.” the American Society for Biochemistry and Molecular Biology.) “If you really want to talk about validation, you Building from the ground up have to start piecemeal,” he says, taking each field on Like a tower, validation is made of a stack of bricks. its own with its quirks and challenges. The first brick is analytical confirmation. This is the Ioannidis agrees that validation has to be tailored type of validation for which researchers have to ask according to the needs of each particular field and the themselves whether they get the same result from types of measurements available. Just take pro- the same experiment done all over again or if a dif- teomics. It may have the mission to use large sets of

16 ASBMB Today April 2012

AT0412_C2C1.indb 16 3/26/12 3:19 PM proteins to understand various biological phenomena, all have to take their roles seriously to ensure that but the data come in a variety of forms, ranging from data are sound. mass spectrometric methods to difference gel electro- But in discussing responsibilities, points of phoresis. Validation issues for various techniques have contention arise. To validate data, researchers need to be dealt with in different ways. access to data collected by others. What kinds of data As Bradshaw points out, “Validation carries with should researchers make available to others? It is it the connotation of replication.” He explains that for important to note, says Robert Chalkley at UCSF, that some -omics fi elds, such as genomic sequencing, “the replication of the data, both from the terms of not every researcher likes the idea of releasing his or technical and biological, is in fact really quite exact.” her data. It’s not just the risk of scrutiny that alarms However, for shotgun proteomics, which identifi es by these researchers but the worry that someone else mass spectrometry a large number of proteins from a may discover something novel in the data that they sample containing millions, “the reproducibility of an missed, which can easily happen with -omics research experiment, even in the same laboratory on the same because the data sets are so large. sample, is only partial,” says Bradshaw. “You can’t talk But even if researchers see the need for releasing about validation [in that case] because of the nature of the data, what should they release? It shouldn’t be large-scale mass spectrometry experiments.” just raw data, argues Baggerly. He says research- Gilbert Omenn at the University of Michigan, the ers also should release the algorithms and codes of chairman of the IOM committee on -omics data validation, agrees with Bradshaw. “It’s extremely impor- bioinformatics tools as well as the metadata, the types tant to recognize you may not get the same result if of information that denote which samples belonged you repeat the experiment in the same lab with the to which groups and how researchers selected those same hands with the same samples, because there samples. Baggerly explains that with -omics informa- is a certain stochastic aspect to detection of peptides tion, “The data are subject to several different types in mass spectrometry,” he says. But he adds it of pre-processing… In many of these pre-processing simply means that there is an even greater need for steps, any one of several different algorithms could be replication with these types of experiments. While employed. There is not yet a consensus as to which there isn’t a one-size-fi ts-all procedure for ensuring one is best.” Because there isn’t a consensus, Bag- accuracy of -omics data, Omenn says that no matter gerly argues researchers have to be explicit in stating the experimental platform, the principles of validation which ones they used. cut across all -omics fi elds. Then comes the big question: Who should bear Who’s responsiBle? the responsibility of collecting, housing and making accessible all that data? In Baggerly’s view, journals Given the magnitude of -omics studies, the responsibility for ensuring that data are valid involves should house the bioinformatics scripts through which everyone, says Omenn. He doesn’t let anyone off researchers ran their data sets for a given publication, the hook: Students, postdoctoral fellows, principal because those codes don’t take up much server room. investigators, departmental heads, institutional But what about raw -omics data fi les, which can be review boards, journal editors and funding agencies gigabytes, even going onto terabytes, in size?

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raW data aCCess Websites like PRIDE collect processed proteomics Access to raw data is a thorny subject. One way to data. But processed data, as Baggerly and Bradshaw illustrate why is to look at proteomics. “Over the years, are keen to emphasize, are not the same as the raw [raw] data have never left the laboratory in which data spat out by analytical instruments. they were collected,” explains Bradshaw. “It has been So in 2010, MCP made it mandatory for its clearly the opinion of a lot of people in the proteomics authors to deposit their raw data fi les in a repository fi eld, and certainly the opinion of the editors of MCP, designed specifi cally for the purpose. One example of that these data need to be put somewhere where they a raw data repository is TRANCHE (https://proteome- can be interrogated by others.” commons.org/tranche/), operated by the laboratory of Philip C. Andrews at the University of Michigan. “For some time, TRANCHE was basically the only show in town,” says Bradshaw. “The problem was that The fi rst cautionary tale in being too hasty TRANCHE’s funding line eventually was dependent on with -omics technologies harks back 10 years. Scientists from the a [federal] grant, which ultimately was not renewed.” U.S. Food and Drug Administration, National Cancer Institute and Over the past year, TRANCHE has struggled, bioinformatics company Correlogic Systems published a paper that because it hasn’t had funding to hire software described proteomic patterns in patients’ serum that seemingly engineers who are needed to maintain it. Because indicated ovarian cancer even at early stages (1). Correlogic Systems of TRANCHE’s technical and fi nancial problems, licensed the technology to Quest Diagnostics and the Laboratory MCP had to put a moratorium on its requirement for Corporation of America to develop a diagnostic test called OvaCheck. depositing raw data. But other scientists set off alarm bells, questioning the analytical The lack of federal support for publicly accessible validity of the study (2, 3). When Baggerly’s team analyzed the data repositories for raw data has researchers vexed. from one of the sets in the paper, Baggerly says by “using electronic TRANCHE isn’t the only example; Omenn, Baggerly noise, we could separate cancers from controls. We should never be and others also point to the Sequence Read Archive, able to do that. The fact that we could was evidence they screwed a repository for next-generation sequencing data, up the [experimental] design.” The FDA, on hearing the reports, which had its funding cut off by the National Center eventually stepped in and insisted on further validation before Ova- for Biotechnology Information at the National Institutes Check was commercialized. of Health last year because of budget constraints (2). The other cautionary tale involves outright fraud. In 2007 and “Funding agencies wish to fund the initial discoveries,” says Evans. For research projects that aim to 2008, Duke University launched three clinical trials based on benefi t patients, just producing those fi rst discover- research led by Joseph Nevins and Anil Potti that used microarrays to ies doesn’t cut it. “You have to spend some time and develop personalized treatments for breast and lung cancer patients money ensuring that validation can be done,” he based on genomic signatures (4). Baggerly once again was involved, explains. “It isn’t as sexy as funding discovery, but along with his collaborator Kevin Coombes, in pointing out various I think funding agencies do have a responsibility to mistakes in the data interpretation (5; to watch a lecture by Bag- encourage and enable validation. Otherwise, we’re gerly on this topic, go to http://videolectures.net/keith_baggerly/). never going to really know which of these discover- But it soon appeared that Potti had lied about his qualiﬁ cations on ies will pan out.” his curriculum vita and the data from his experiments were riddled with errors. In 2010, Duke University halted the clinical trials. So far, nine of the Nevin and Potti publications, including reference 4, have been retracted (6). CBS’s “60 Minutes” aired a segment on the Duke case on Feb. 12 (www.cbsnews.com/8301-18560_162-57376073/ deception-at-duke/). referenCes 1. Petricoin, E.F. et al. Lancet 359, 572 – 577 (2002). 2. Sorace, J.M. & Zhan, M. BMC Bioinformatics 4, 24 (2003). 3. Baggerly, K.A. et al. Bioinformatics 20, 777 – 785 (2004). 4. Potti, A. et al. Nature Medicine 12, 1294 – 1300 (2006). 5. Baggerly, K.A. & Coombes, K. R. Ann Appl Stat 3, 1309 – 1334 (2009). 6. http://dukechronicle.com/article/ninth-potti-paper-date-gets-retracted.

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And unlike funding discovery-driven research, to the Advisory Committee to the Director to help points out Aebersold, it’s not going to cost federal inform NIH policy on data management. The com- Rajendrani Mukhopadhyay ([email protected]) agencies millions of dollars to build and maintain mittee is expected to make its recommendations in is the senior science writer repositories for raw data. Creating infrastructure for June of this year. for ASBMB Today and the data deposition is “not cheap but it’s also not astro- But Bradshaw cautions that having access to the technical editor for the Journal of Biological Chemistry. nomical,” he says. “It’s certainly a serious effort, but raw data won’t be the entire solution to validation. it’s not something that would bankrupt the NIH.” Raw data access is “not a panacea, but it will make it A great example that benefi tted from public easier to go in and look at what different people col- access to data is the Human Genome Project. The lected under different conditions,” says Bradshaw. organizers of the federally funded project “demanded that data be uploaded, even at a time when the data moVing ahead were riddled with errors,” says Omenn. “It helped Experts in this story all cited the volume of -omics

clean up the data, because people weren’t hiding it data as a cause of concern for validation. But referenCes in their own computers!” Because other research- Matthias Mann of the Max Planck Institute of 1. Ioannidis, J.P.A. & Khoury, M.J. Science 334, 1230 – 1232 (2011). ers were able to examine, test and validate the data, Biochemistry in Germany is hopeful that the data 2. www.nlm.nih.gov/pubs/techbull/jf11/ genomics has been able to move forward onto whole- volume issue will someday be more manageable. jf11_ncbi_reprint_sra.html. genome sequencing, genomewide association studies Right now, the data volume is an indication of the and other endeavors. complexity of biology, but some of the complexity of When asked to respond to these views of aca- biology comes from interconnections between differ- demic researchers, Lawrence Tabak, a co-chair of the ent molecular pathways, cells, tissues and organs. NIH Data and Informatics Task Force and the Advisory “I think we will see in the future that many of the Committee to the Director, NIH Data and Informatics biological changes are not independent of each other Working Group, provided a statement. “Data sharing but they go together,” he says. “That means the is critically important to the advancement of biomedi- dimensionality of what we are measuring is actually cal research, and NIH is committed to supporting the lower… That inherently reduces the complexity.” But collection, storage and sharing of biomedical research he cautions, “Until we know more and have mapped data. The astonishing increase in the amount of data it all out, we will be swimming” in data. being generated through NIH-funded research is The boundaries of biomedical science can’t be an indicator of the extraordinary productivity of the pushed forward without proper validation steps, research enterprise,” he said. “Yet with this astonish- which have to be integrated in all stages, from ing increase, the agency is facing signifi cant data fundamental research to clinical trials and popula- management challenges. Given how extremely ben- tion studies, say Ioannidis and Khoury. Aebersold efi cial the availability of large datasets is to advancing points out that researchers suffer from lost money, medical discoveries, ensuring its continued availability resources and time if they chase mirages in data. is a high priority for NIH.” And the repercussions of improper validation are Tabak, who is also the NIH principal deputy direc- magnifi ed if research has medical applications. As tor, went on to say that the NIH director has formed Evans puts it, “You get validation wrong, and people an internal working group as well as a working group will literally suffer.”

April 2012 ASBMB Today 19

AT0412_C2C1.indb 19 3/26/12 3:20 PM Annual Meeting Special Events

Career Speed Dating Teaching Session Effectively Communicating SATURDAY, APRIL 21 • 4:45 – 5:45 P.M. with Stuart Kornfeld: Your Science SAN DIEGO BALLROOM A, MARRIOTT MARQUIS HOTEL Modeling the Molecular Machinery Sponsored by the ASBMB Public Affairs Advisory Committee Find your perfect career match at this professional- of the Protein Traffi cking Pathway MONDAY, APRIL 23 • 12:30 – 2 P.M. development session for undergraduates. Experts SUNDAY, APRIL 22 • 1:30 – 2:30 P.M. CONVENTION CENTER, 6B, UPPER LEVEL in patent law, tech transfer, K – 12 education, science CONVENTION CENTER, 6B, UPPER LEVEL It has never been more important to communicate policy and seven other fi elds will be available to This informal session will provide students and science and its value to the public. How can we discuss exciting career opportunities at the bench postdocs the opportunity to meet and visit make scientifi c discovery a high national priority? and beyond. with Kornfeld and other researchers who have What can each of us do to make a difference? contributed to the fi eld of protein traffi cking. This panel features Nobel laureate Paul Berg, Brekke for Next Gens Physical models of key proteins involved in National Public Radio science correspondent Joe SUNDAY, APRIL 22, AND MONDAY, APRIL 23 • 7 – 8 A.M. protein traffi cking pathways will be available — Palca, Deputy Director of Practices, Synthetic CONVENTION CENTER, ROOM 11A, UPPER LEVEL and will frame these conversations about the Biology Engineering Research Center (SynBERC), Join Kim Orth on Sunday and Bettie Sue Masters recent discovery of essential features of the Megan J. Palmer, Huffi ngton Post senior science on Monday for breakfast to discuss science and traffi cking pathway. correspondent Cara Santa Maria, and moderator and scientifi c careers. The event is free but open to ASBMB President-elect Jeremy Berg. undergraduates only. Preregister at www.asbmb. ASBMB Welcome and org/breakfast. Networking Reception Lipid Droplets: Sponsored by the ASBMB Minority Affairs Committee Basic Working Principles Workshop on LIPID MAPS SUNDAY, APRIL 22 • 6:30 – 8:30 P.M. MONDAY, APRIL 23 • 12:30 – 2 P.M. MARRIOTT MARQUIS HOTEL, CONVENTION CENTER, 11A, UPPER LEVEL Lipidomics Tools MARINA BALLROOM D, SOUTH TOWER Our partner for this workshop is Avanti Polar Lipids. SUNDAY, APRIL 22 • 12:30 – 2 P.M. CONVENTION CENTER, 11A, UPPER LEVEL The ASBMB Minority Affairs Committee Lipid droplets, organelles found in cells of welcomes primary investigators, industry Lunch provided for fi rst 35 attendees vertebrates, invertebrates and plants, have received professionals, educators, young scientists and This workshop should be of interest to much attention of late because of their importance students to enjoy this networking and mentoring lipidomics researchers and bioinformaticists. in lipid-based diseases, in host–pathogen reception featuring research posters by the 2012 It will highlight the diversity and unique interactions and in the production of biofuels. Graduate Minority Travel Award recipients. structural and biochemical challenges of the This workshop will focus on the working principles lipidome and will provide users with a suite and methodologies of lipid droplet research. of convenient online tools for the purpose of information retrieval and lipidomic data analysis.

AT0412_C2C1.indb 20 3/26/12 3:20 PM Annual Meeting Special Events

ASBMB Scientifi c Work-Life Balance Thanks to our sponsors Fermentation Hour and Time Management: MONDAY, APRIL 23 • 6 – 7 P.M. A Professional Development Workshop for CONVENTION CENTER, Students, Postdocs and Junior Faculty WEST TERRACE (BAYSIDE), UPPER LEVEL TUESDAY, APRIL 24 • 12:30 – 1:30 P.M. Relax at this casual post-session happy hour and CONVENTION CENTER, 11A, UPPER LEVEL continue the scientifi c discussion, meet the speakers * Advance registration and fee required. and network with others in your fi eld. Suzanne Pfeffer, ASBMB’s president, will engage participants in a discussion to address work–life FASEB ASBMB Poetry balance and the practice of successful time Contest Reading management to achieve and sustain personal MONDAY, APRIL 23 • 7 – 7:30 P.M. and professional satisfaction. CONVENTION CENTER, 6A LOBBY AREA, UPPER LEVEL Join us in support of our prize-winning poets ASBMB Women Scientists and the runners-up, who will read their science- Networking Event themed verses for all to enjoy. TUESDAY, APRIL 24 • 6 – 8 P.M. CONVENTION CENTER, 11A, UPPER LEVEL Brewing Science, Join fellow women biochemists and molecular ASBMB Tweet & Meet biologists for a topical discussion of how women MONDAY, APRIL 23 • 7:30 – 9:30 P.M. scientists can better support each other. Featured MISSION BREWERY, 1441 L. ST. presenters: Ellen Daniell, author of “Every Other Looking to learn how to share your science in an Thursday: Stories and Strategies from Successful Internet 2.0 world? Need practice communicating Women Scientists,” and Christine Guthrie, ASBMB- your science to lay audiences? Just like beer? Then Merck Award lecturer. join us for Brewing Science, an informal tweet- and-meet blend of scientists, communicators and concerned constituents.

AT0412_C2C1.indb 21 3/26/12 3:20 PM Science in stanzas

Congratulations to the prize winners and runners-up in the ASBMB Today poetry contest coinciding with the society’s annual meeting and the Experimental Biology 2012 conference to be held April 21–25 in San Diego. We look forward to showcasing the top poems at a public reading at 7 p.m. April 23 in the convention center 6A lobby on the upper level.

SECOND PLACE Angiogenesis Cheryl Ainslie-Waldman, University of Minnesota A hiccup of the cells FIRST PLACE mantelpiece clock that needs no winding perfused by gears and cogs and wires Lost in Translation that drive their stake into the earth. Andrew Brown, The University of New South Wales A tumor formed from two The patient is resting and Hope attends and borne by one. as a silent witness at her vigil. Alien at ﬁ rst Both can but wait. Patiently. an invader welcomed with snakelike tendrils Her raw red eyes will curling up and in and around the bands to separate. to deliver maternal blood. Her labcoat weighs heavy The DNA aligns itself on shoulders hunched over the apparatus. and reveals political intentions. Her gloved hands ache from pipetting. A being never to be seen or heard or touched Not long now. will kill by its love Soon she will be in the darkroom and mistaken creation. ﬁ xated on the developer waiting two dry-mouthed minutes. Soon the Moment of Truth (or at least something approaching it) Will the results herald a Miracle Cure? A Medical Breakthrough? Snag her a slot on the Sunday news? But she’s dreaming not of the lucre, the Lasker, Cell and celebrity. She dreams only of…

Amongst the twinkling snoring machines Her eyelids droop her head drifts down And there is Hope that she won’t drool As she dreams (from bench to bedside) o nly of Sleep.

AT0412_C2C1.indb 22 3/26/12 3:20 PM THIRD PLACE Ode to the Lab Jesus Manuel Ayala Figueroa, University of Puerto Rico at Humacao O laboratory! How sublime is your splendor! Microscopes, benches and gadgets garnish your space. The smell of the agar, the color of your solutions— Oh how magnifi cent this place is! It is within these walls that I want my bed always to be. The mere mention of your name evokes happiness, HONORABLE MENTION For it is within these walls that great things occur. Your inhabitants have sworn to advance humanity’s greatness. How… Understanding It is here that great minds concur. Karen Hecht, University of Pittsburgh Days, months or years; time matters not. How brightly do cells glow I can spend my life enjoying these blots. In a dark fi eld? O Morpheus, never wake me up from this dream! Winking back at the objective Because here is where I want my bed always to be. What shapes do proteins take Rejoice if it’s wrong, celebrate if it’s right— In a CHARMMed sea? The thrill of experiment, the researcher and its might. Folding back that which was unknown Ideas bend, change and collide. When do signals fi re My only desire is to have my bench to bedside. In salty streams? Shouting out all their potential Where does a Drifter go In fl edgling fl ight? Expressing what moves us forward Why do these codes unfurl In charged currents? HONORABLE MENTION Spilling secrets to those who ask Song of Sanger Who devours these whispered words Gail S. Begley, Northeastern University With swelling thirst? They fi ll my heart with joy, Living life through understanding These jagged peaks that cross my screen, No mere Gs, Cs, As and Ts, But mounts of blue, black, red, and green. What mysteries will their sequence yield EDITOR’S CHOICE About my very favorite gene? Consistent with this, cell extracts from the iba57∆ strain showed virtually no aconitase activity (Fig. 2A). Cristy Gelling, University of Pittsburgh In a well-lit, windowless cupboard alone with a chirping machine, a bucket of melting ice and a persistent smell, I danced.

AT0412_C2C1.indb 23 3/26/12 3:20 PM Mobile Apps For Annual Meeting Attendees

PRODUCTIVITY TRANSPORTATION Experimental Biology 2012 San Diego Metropolitan Use the EB2012 app to get session information, make Transit System your itinerary and navigate the convention center. Make sure to download the bus and trolley map Download it: http://crwd.cc/eb2012 before snagging yourself a $5 day pass. Get it at the Android market: http://bit.ly/Ala81V OnLive Desktop Make keeping up with work while at the meeting Taxi Magic a little easier by downloading this free iPad app. It If the ASBMB fermentation hour offers access to Microsoft Ofﬁ ce 2010 with 2 GB of cloud or brewery tweetup has gone to storage and Internet Explorer with Adobe Flash. your head, this app will help get Find out more: http://desktop.onlive.com/ you back to your accommodations in a tap. Available on multiple platforms: http://taximagic.com/ Journal of Biological Chemistry Don’t forget that the JBC’s iPhone app allows you to scan the latest issue, special collections and Papers in Press. Get it on iTunes: http://bit.ly/x7yreC FOOD & DRINK Yelp This restaurant and store review app is NEWS & VIEWS good for foodies everywhere, but it will be especially useful for those foragers forging San Diego Union-Tribune paths unknown in San Diego. This one’s for the Available on multiple platforms: www.yelp.com/yelpmobile news junkies: the Pulitzer-prize winning OpenTable newspaper’s free app. Make reservations for restaurants while Get it at iTunes: http://bit.ly/tbNveM on the go and forward the details to members of your dining party. Available on multiple platforms: www.opentable.com/mobile/

AT0412_C2C1.indb 24 3/26/12 3:20 PM Mobile Apps For Annual Meeting Attendees

LEISURE Balboa Park If you decide to head out to Balboa Park’s 1,200 acres Beauregard, a 13-year- of beauty and culture, this free app will guide you. old snow leopard, arrived at the San Diego Get it on iTunes: http://bit.ly/bS7ZOP Zoo over the winter to breed with the zoo’s 8-year-old female snow leopard, Anna. PHOTO: KEN BOHN, SAN DIEGO ZOO

San Diego Zoo If the meeting isn’t wild enough for you, this free app from the fabulous San Diego Zoo offers photos, videos, live animal cam action, details about the residents on exhibit and visitor info. Get it at the Android market: http://bit.ly/wrNham Get it on iTunes: http://bit.ly/uN3pxk

#EB2012: DON’T FORGET TO USE IT! FOLLOW ASBMB’S OFFICIAL Annual meeting attendees who are on Twitter will want to use the MEETING BLOGGER #EB2012 hashtag so that their quips are indexed and retweetable. If Heather Doran, a Ph.D student in medical you tag @ASBMB in your tweet, we’ll do our best to retweet you to our sciences at the University of Aberdeen, will be followers. If Twitter isn’t your thing, we’ll the society’s ofﬁ cial EB2012 meeting blogger. also be broadcasting on our Facebook She is a passionate science communicator, writer Follow @asbmb page: www.facebook.com/asbmb. So, and editor for Au Science Magazine. Keep an eye make sure to become a fan and ping us if on her blog at http://ausm.org.uk or follow her at #EB2012 we can be of any assistance. on Twitter at www.twitter.com/hapsci.

AT0412_C2C1.indb 25 3/26/12 3:20 PM essay

Tribute to midlevel scientists Let’s acknowledge and reward the burgeoning class of highly skilled, underpaid and highly stressed workhorses in our nation’s research laboratories BY LYNN ZEChIEDRICh

hey are not often the fi rst or last authors on publi- offer him a raise last year because of a wage freeze, I tcations. They are not usually the ones traveling to asked Jamie what I could do to let him know how much meetings to present their work. They do not often get I appreciate him. I expected to hear something like “an to interact with the public or the press. Their jobs are offi ce,” “a closer parking spot” or “a better title.” His reply tenuous, and their titles rarely refl ect their talent, intellect illustrates why he, and those like him, are so valuable to or hard work. In the U.S., they are known variously as research laboratories and institutions: “I would like to give instructors, nontenure-track faculty, postdoctoral fellows, a lecture in one of your classes. I love teaching.” research faculty, senior technicians or staff scientists. Although they were not likely hired purposefully to They were always a part of laboratory groups, but occupy this niche, without people like Jamie in the middle as the economy has stumbled and the job market has ranks, less work would be done, fewer grants would be tightened, fewer postdoctoral fellows have landed the written, trainees would be less well trained and more previously typical positions befi tting their laboratories would be closing. The middle training. As a consequence, increasing ranks bring their knowledge and expertise. numbers of highly skilled workers have They bridge the gaps between the more become stuck in their training laborato- transient laboratory members and the boss, ries. The reasons people get stuck often and they bring the freedom to work on include life events that can strike anyone long-term goals, those that might not lead at any time: illness, divorce, natural disas- to immediate or as frequent publication but ter, or long-term or challenging projects that eventually might have greater impact. that failed to yield suffi cient numbers of Especially in today’s fi nd-the-next- publications. superstar job searches that tend to select Sometimes it’s a matter of choice. those few people who have not yet been Trainees observe the stress on the boss, struck by normal life events, a lot of great particularly the lack of time, and they talent is accumulating in the middle ranks choose not to progress to that next Jamie Catanese of institutions. Both those who have step— not if that step means less time become stuck and those who have pur- with family and loved ones, neglecting outside interests posefully chosen not to move on bring much good to that are meaningful to them or giving up a long-term our nation’s laboratories and institutions. project with potential high impact. Why not consider today what these scientists bring In my group, Jamie Catanese chose to stay. He to your group, department or institution and then ask wants nothing to do with my “crazy hours, stress or them what you can do to help make them feel valued? constant grant-writing.” Now a senior staff scientist, Being aware of the advantages and rewarding their Jamie trains graduate students and postdoctoral fellows dedication and skill just makes sense. while carrying out several of his own long-term research projects. One of these projects, new potential therapies Lynn Zechiedrich ([email protected]) is a professor for lung cancer, is personal for Jamie: His mother died in the departments of molecular virology and from the disease. microbiology, biochemistry and molecular While jobs have become harder to fi nd, the demand biology, and pharmacology at Baylor College on the people in those jobs has increased. Unable to of Medicine in Houston.

26 ASBMB Today April 2012

AT0412_C2C1.indb 26 3/26/12 3:20 PM lipid news A report from the ASBMB Lipid Division. Are we doing a good job of teaching the groundbreaking research of our predecessors? BY DENNIS VANCE

ome time ago, I was present- panion paperback collection Sing a lecture on cholesterol of key papers in biochemistry. biosynthesis in an advanced Thus, it was easy for students course on lipid and lipoprotein to read and digest the experi- biochemistry. I mentioned that ments that led to key fi ndings. Konrad Bloch did key research In 2012, such a collection of from the 1940s to the 1970s. papers is not necessary. All we “Have any of you ever heard of need to do is provide the refer- Konrad Bloch?” I asked. I was ences, and students will be able rather surprised that the students to access most of these papers did not know about Bloch or his on the Internet. Most students contributions. probably will not bother to Of course, it is possible that review these original papers. Bloch’s fundamental contributions However, shouldn’t we provide were taught and the students guidance to those students who simply forgot. Alternatively, they do care? may never have been taught While we need to teach the about his important discoveries. basic language of lipid research In either case, this is very unfor- To read the Journal of Biological Chemistry (i.e., structures, pathways, Classic article “The Biosynthetic Pathway for tunate. In my view, as teachers of Cholesterol” about Konrad Bloch, visit http:// enzymes, genes, regulation), biochemistry, we are not instruct- bit.ly/ys2FKN. one of our major objectives ing our students properly. should be to convey to the Some will argue that there is already too much to students the sense of discovery and awe in lipid bio- cover when we teach biochemistry and we don’t have chemistry and expose students to how we know what time to provide a historical perspective. I don’t buy this we know. We need to reiterate the scientifi c method argument. We need to bring lipid biochemistry to life for testing hypotheses. It seems to me the best way to for our students. The students should appreciate the start the teaching process is to introduce the stars of key scientists who laid the foundations for the current the past. Who were these scientists? What questions developments in the subject. It is also instructive to did they ask? How did they obtain the answers? describe some of the experiments these scientists did. If this teaching approach were introduced, we Bloch conducted very elegant experiments using heavy might be pleasantly surprised the next time we isotopes and radioisotopes to delineate the pathways asked students, “Who was Konrad Bloch and what of cholesterol biosynthesis. If one or two of these did he do?” experiments were described, it would help the students understand how tracers are used in biochemistry. In the last millennium, I contributed the lipid chap- Dennis Vance ([email protected]) ters to the textbook “Biochemistry” edited by Geoffrey is a distinguished university professor at the Zubay. We made an effort to present a historical per- department of biochemistry at the Faculty of spective. A unique feature of the textbook was a com- Medicine & Dentistry at the University of Alberta.

April 2012 ASBMB Today 27

AT0412_C2C1.indb 27 3/26/12 3:20 PM journalnews More ASBMB journal highlights at www.asbmb.org.

out to be effective strategies to treat these devastating THE JOURNAL OF conditions,” says Wang. But, he cautions, fi rst “we need to BIOLOGICAL CHEMISTRY learn more about normal functions of TDP-43.”

Rajendrani Mukhopadhyay ([email protected]) is the senior science writer for ASBMB Today and the technical editor for Worm protein provides the Journal of Biological Chemistry. insight into aging and referenCe neurodegeneration 1. Zhang, Tao et al. J. Biol. Chem. 11, 8371 – 8382 (2012). BY RAJENDRANI MUKhOPADhYAY

Humans carry an RNA-processing protein called the THE JOURNAL OF transactive response DNA-binding protein, or TARDBP/TDP- LIPID RESEARCH 43. The protein has been linked to a number of neurodegenerative disorders that involve protein misfolding, such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration. In a From the inside out recent “Paper of the New study gives clues on how Week” published in the the only FDA-approved drug to treat Journal of Biological primary biliary cirrhosis works in the liver Chemistry, Jiou Wang BY MARY L. ChANG at The Johns Hop- A small amount of ursodeoxycholic acid, also known as kins University and UDCA or ursodiol, has been a component in Chinese tradi- colleagues described tional medicine treatment for liver disorders for centuries. a Caenorhabditis In the Western world, UDCA is the only approved drug elegans model in to treat primary biliary cirrhosis, an autoimmune disorder which they removed characterized by progressive damage to the bile ducts the worm version of within the liver, causing a buildup of cholesterol in the liver the TDP-43 protein, and subsequent called TDP-1 (1). liver damage. Why the worm? “Although mammals Without treatment, such as mice offer most patients with important models this condition will for human diseases, need a liver trans- sometimes the complexity of the mammalian systems plant later in life, prevent the unraveling of basic functions of a molecule,” and a quarter of explains Wang. “For example, the TDP-43 knockout mice patients who have die in early embryogenesis, making it diffi cult to tease out had the condition the physiological functions of the protein.” for more than 10 Wang’s team showed that the worm and human versions years will suffer of the RNA-processing protein were very similar. Worms liver failure.UDCA missing TDP-1 suffered from problems with fertility, growth also has been and movement, but, intriguingly, they lived longer. The shown to prevent mutant worms were also more resilient against the toxic the progression of effects of misfolded proteins. The investigators concluded colorectal cancer that TDP-1 regulates protein homeostasis and aging and the recurrence through RNA processing. of colonic dysplasia, the development of precancerous, Because protein homeostasis and aging are com- abnormal cells in the colon. But the mechanism by which mon themes in many age-dependent neurodegenerative UCDA counteracts these liver problems hasn’t been com- diseases, “we are hopeful that interventions that improve pletely elucidated. protein homeostasis or delay aging might eventually turn In their paper entitled “Ursodeoxycholic acid binds

28 ASBMB Today April 2012

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ileal bile acid binding protein” to be published in the April issue of the Journal of Lipid Research, Changming MOLECULAR & CELLULAR PROTEOMICS Fang and colleagues at the Cancer Research Center at the Sanford-Burnham Medical Research Institute in La Jolla, Calif., set out to determine if ileal bile acid bind- Serum antibodies ing protein, or IBABP, a cytosolic protein believed to be as biomarkers involved in the absorption of bile acids associated with BY RAJENDRANI MUKhOPADhYAY the processing of dietary fat, is involved with UCDA’s activity in the human body (1). The scientifi c literature contains more than 100,000 reports Major human bile acids bind to two sites on IBABP of biomarkers, but only 43 have been approved by the U.S. and act in a cooperative manner in healthy individuals. Food and Drug Administration for clinical diagnostics (1). A In contrast, they found by tryptophan ﬂ uorescence spec- problem is that most biomarkers are so dilute in blood that troscopy that UCDA only binds to a single site. Further, detecting them becomes a needle-in-haystack issue. Phillip when IBABP was saturated with UDCA, the affi nity of Stafford and colleagues at Arizona State University and the University of Arizona have instead been pursuing antibod- IBABP for major human bile acids increased two- to fi ve- ies as disease indicators, an idea fi rst proposed by Abner fold, and UDCA was shown to bind cooperatively with Notkins of the National Institutes of Health (2). a major human bile acid bound to the other binding site Antibodies are abundant and stable in serum and easily just as two bile acids normally do while sitting in these detected. Stafford says his group had discovered that with binding sites. antibodies they could predict a number of infectious, chronic IBABP also associates with farnesoid X receptor and autoimmune diseases. “We could even predict trans- alpha, or FXRα, and had been assumed as a mediator plant rejection,” says Stafford. “I’ve no idea why this [notion] of this receptor’s activity. While it is still not clear how didn’t catch on earlier.” this mediation occurs, Caco-2 cell culture results from Because antibodies readily cross-react with random pep- this study indicate IBABP is involved in UDCA’s effect to tide sequences, Stafford and colleagues demonstrated in a increase the activation of this receptor. Further research recent Molecular & Cellular Proteomics article that microar- is needed to determine IBABP’s precise mechanism of rays with 10,000 random peptides served as an effective action. and simple way to capture antibodies from serum to reveal a This article highlights the importance of considering patient’s health history (3). For instance, they found antibod- IBABP’s activity and role in UDCA’s potential benefi ts in ies against a newly developed disease or a recent vaccina- patients with liver damage. UDCA increases the binding tion dominated over antibodies from an older disease. of major human bile acids; this decreases the number of “I hope people start to use this technology, because it free bile acids in cytosol, reducing stress on the gas- holds enormous promise for diagnostics,” says Stafford. The group is now working on making microarrays with tens of trointestinal system and preventing bile acid-induced millions of peptides because “the more mutations and the development of bile peptides you can examine, the better you acid resistance seen in colorectal can- can dissect a disease, and you gain a cer. The authors suggest that, based measure of sensitivity as well,” explains on their observations, when FXR ’s α Stafford. He adds, “We’re also work- activation is enhanced in the presence ing on fi eld units so you can take this of UDCA bound to IBABP, more major technology on-site for rapid diagnosis or human bile acids are released from biothreat detection.” cells called ileocytes, which are otherwise held back in liver disease and can Rajendrani Mukhopadhyay (rmukhopadhyay@ asbmb.org) is the senior science writer for cause cirrhosis. ASBMB Today and the technical editor for the Journal of Biological Chemistry. Mary L. Chang ([email protected]) is managing editor of the Journal of Lipid referenCes Research and coordinating journal manager 1. U.S. Food and Drug Administration. www.fda.gov/Drugs/ of Molecular and Cellular Proteomics. ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm. 2. Notkins, A. L. “New Predictors of Disease.” Scientiﬁ c American, March 2007. referenCes 3. Stafford, P. et al. Mol. Cell. Proteomics. doi: 10.1074/mcp. 1. Fang, C. et al. J. Lipid Research. doi: 10.1194/jlr.M021733 (2012). M111.011593 (2012).

April 2012 ASBMB Today 29

AT0412_C2C1.indb 29 3/26/12 3:20 PM minorityaffairs Navigating the NIH grant-application process BY SONIA C. FLORES

f your career goal is to perform biomedical research, then Submits grant NIH Center for Scientific Iyou should read this article. Here, I’ll try to help you navi- application to NIH Review assigns application electronically to institute/center and IRG gate the grant application and review process and hope- fully guide you to a successful submission. I will address only applications to the National Institutes of Health, Scientific Review Groups because, frankly, this is what I know. There are many more evaluate the application’s funding agencies, but the NIH is where the bulk of the scientific merit

money is. Investigator 2 – 3 MONTHS The NIH has a complex organizational structure (www. AFTER SUBMISSION nih.gov/icd) made up of institutes or divisions with their An advisory council or board own research interests. When the application is submit- recommends approval

ted, it is first reviewed by the Center for Scientific Review; 2 – 3 MONTHS

based on the content of the abstract, a program officer AFTER SUBMISSION at the CSR assigns the grant to an Integrated Review RESEARCH Institute staff prepares Group (a study section) and an institute or center. If you IDEA funding plan for director want your application to be assigned to a specific institute or study section, make sure the first or last sentences of the abstract have keywords aligned with those research interested in your area and qualified to judge your work interests. There may be some overlap between study sec- is essential. While gathering the information to make an tions, and you are allowed to request a study section in informed request takes work, many investigators feel it’s the cover letter. worth it. Research the interests of each study section to About two to three months after submission, the see where your application would fit best, and look at Scientific Review Groups evaluate the scientific merit of review rosters to see who is on the committees. Remem- the grant. After another two to three months, an advisory ber that it is not easy to tell who will review the application, council or board recommends the grant for approval. After because many applications are now reviewed by fluid ad- approval, the institute staff prepares a funding plan for the hoc, special-emphasis panels. director, the institute allocates the funds and the grantee begins conducting his or her research. (See figure.) Meeting deadlines The NIH has three grant cycles that may vary depending Writing a cover letter on the type of grant. It is important to observe the dead- to request a study section lines. If your grant is submitted after the deadline, it may Your cover letter should include the following: application not be reviewed until the next review cycle. Find grant title, institute request (it’s best to choose three, but you deadline information at www.nih.gov/grants/funding/ need to prioritize ), IRG request (get advice from your submissionschedule.htm. program officer on this), and any other special requests. Information on institute requests can be found at Strategies for planning a grant www.nih.gov/icd and on study sections at www.csr.nih. Write an outstanding application that will appeal to review- gov/Roster_proto/sectionl.asp. ers, who serve as judge and jury. Write from the perspec- Having your application assigned to the right study tive of a screenwriter and not from the perspective of a section ensures that the appropriate people review your novelist. A grant is presented to a panel of peer reviewers application. The NIH generally honors requests for study by one primary person and two helpers, so you want to sections. It is important to frame your request in positive write a script that will facilitate presentation of your pro- terms. Mentioning that a study section has several people posal to the rest of the panel.

30 ASBMB Today April 2012

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There are eight main steps to follow Each aim should be a specifi c test of the overall when planning your grant. hypothesis. Organize and defi ne your aims so that you 1. Check out the competition and see which projects in can relate them directly to your research strategy. your fi eld are being funded. Search the NIH RePORTER The “Research Strategy” section includes the following: database at http://projectreporter.nih.gov/reporter.cfm. 1. Signiﬁ cance 2. Evaluate yourself: How do your strengths match the topics found in step 1? Can you capitalize on your expertise and fi ll a. Explain the importance of the problem or critical barrier to in gaps with mentors, collaborators or consultants? Do you progress in the fi eld that the project will address. have a niche? If not, fi nd one! b. Explain how the project will improve scientifi c knowledge, technical capability and/or clinical practice in one or more 3. Determine available resources and support from your broad fi elds. school. c. Describe how the concepts, methods, technologies, 4. Brainstorm with colleagues and mentors, and have treatments, services or preventative interventions that drive knowledge of the relevant literature! this fi eld will be changed if the aims are achieved. 5. Write a hypothesis for your proposal in 25 words or fewer; 2. Innovation edit, edit and then edit again. a. Explain how the application challenges and seeks to shift 6. Give yourself time to write and rewrite the application. research or clinical-practice paradigms. 7. Utilize any form of pre-peer review that you can fi nd (e.g., a b. Describe novel theoretical concepts, approaches or mock study section, a class). methodologies, and instrumentation or intervention(s) to 8. Follow all instructions to the letter: Poor formatting, illegible be developed or used and any advantage over existing fi gures, wrong fonts and poor grantsmanship will turn methodologies, instrumentation or intervention(s). reviewers off! c. Explain refi nements, improvements or new applications of theoretical concepts, approaches or methodologies, Writing a solid hypothesis instrumentation, or interventions. Most top-notch grant applications are driven by strong 3. Approach hypotheses rather than advances in technology. Applica- a. Describe the overall strategy, methodology and analyses to tions should ask questions that prove or disprove a hypoth- be used to accomplish the specifi c aims. Provide evidence esis rather than use a method to search for a problem of feasibility— not a miniature version of the proposed study. or simply collect information. If your application is not b. Discuss potential problems, alternative strategies and benchmarks for success anticipated. hypothesis-based, state that it isn’t and give your reasons why the work is important (e.g., X-ray crystallography, or Crafting your biographical sketch perhaps it’s a training grant). Choose an important, test- The bio sketch requires a personal statement that briefl y able, focused hypothesis that increases understanding of describes why your experience and qualifi cations make you biological processes, diseases, treatments or preventions. particularly well suited for your role in the project. A strong hypothesis should be based on previous research. having your application scored Reiterate your hypothesis throughout the grant using differ- The IRG will review your application and assign it a score ent wording. from 1 – 9. A score of 1 is the highest, given to a grant con- Planning your application sidered exceptionally strong with essentially no weaknesses; Ask yourself these questions: Why is this project important? 9 is considered poor, with very few strengths and numerous Why are you the right person to conduct this research? major weaknesses. Required sections of a grant are “Specifi c Aims” (one In summary, a great proposal is a solid, exciting idea that page long) and “Research Strategy” (the new format has a is well expressed with a clear indication of methods for pur- 12-page maximum). suing the idea, evaluating the fi ndings, making them known “Specifi c Aims” should include the following: to all who need to know and— for the NIH— indicating the 1. One to two paragraphs that develop the conceptual overall impact to the scientifi c community. framework of the proposal. These should describe previous studies in the area, identify the gaps the research will address and end with a statement of your hypothesis or Sonia C. Flores (sonia.fl [email protected]) is a overall objective. member of the ASBMB Minority Affairs Committee 2. A set of aims designed to answer the questions posed and a professor of medicine at the University of by the hypothesis. The important word here is “specifi c”! Colorado Denver, Anschutz Medical Campus.

April 2012 ASBMB Today 31

AT0412_C2C1.indb 31 3/26/12 3:20 PM education and training Indications of a bright Types of academic R&D U.S. R&D expenditures, expenditures, 2009 2009 (% of $400.5B)

Dev. 3.5% future through science Other* 3.8% Nonproﬁts* 4.4% By Michael J. Bradley Federal gov.

7.7% s scientists and science educators, we strongly value rational decision making based on reliable data. A Applied research Both in and outside of academia, we depend on research 21.9% and development and education funding from a variety Academia* of sources to conduct our work. As we perform research 13.6% Industry, and teach science, we mentor and advise students at funded by industry Basic research many levels of training and expertise on why and how to 60.6% 74.6% become a practicing scientist. One source of current and Industry, reliable data with which to reinforce both our funding justi- 9.9% fications and our education and professional development federally funded advice is the biennial Science and Engineering Indicators from the National Science Board, the governing body of the National Science Foundation. The SEI are factual and governing policy-neutral. Here, I’ll highlight a few points from the 2012 SEI that influence several aspects of my own scientific career development and the advice I give to attaining and maintaining a level of R&D investment equal aspiring scientists (1). to 3 percent of GDP (1). As the U.S. competes globally for KTI market share and aims to attract, train and retain Scientific investment and the U.S. economy the best and brightest human capital, it is critical that our In this election year, with tight budgets in both the U.S. nation expand R&D expenditures at rates that will stay government and private industry, how do we justify our near or above 3 percent of GDP over the long term. investments in R&D? According to the 2012 SEI, the U.S. has spent about $400 billion on R&D in each of the Educational investment on a personal level past few years, with industry contributing 62 percent, the In the early spring of my senior year in high school (14 federal government 31 percent, nonprofits 3 percent, col- years ago now), my parents and I visited several Midwest leges and universities 3 percent, and nonfederal govern- colleges to which I had been accepted. Given that my ments 1 percent. parents weren’t in a financial position to put me through The most important justification for continuing and college, a difficult decision arose. I had a comparatively increasing these expenditures comes from considering cheap option, thanks to scholarships, where the biochem- that fields based in science, technology, engineering and istry professor assured my father that I would be a “big mathematics, collectively referred to as “knowledge- and fish in a small pond.” At a decidedly higher caliber but technology-intensive industries,” or KTI, contributed about more expensive school, a biochemistry professor talked 40 percent of the $14-trillion-plus U.S. GDP in each of about the challenges and rigor of the program along with the past few years (1). As today’s KTI investments lead the high expectations of the faculty members and the to tomorrow’s breakthroughs, our nation’s total annual superior capabilities and track records of typical students R&D budget currently affords a 14:1 return on investment. there. The clincher for my father was when he said, “Don’t That’s comparable to the investment returns from building just consider the tuition costs over the next four years but the U.S. interstate highway system (2). Today, our current also the opportunities that will help your son develop a R&D investments constitute 2.8 percent of U.S. GDP. To satisfying and financially rewarding lifelong career.” put this in perspective, several other countries, including I eventually chose both the more challenging school and the members of the European Union, have set goals of a career in science, and I have remained very happy with

32 ASBMB Today April 2012

AT0412_C2C1.indb 32 3/26/12 3:20 PM education and training

Types of academic R&D U.S. R&D expenditures, * These sectors have signifi cant federal funding to varying expenditures, 2009 2009 (% of $400.5B) levels. In particular, the funding for R&D in academia breaks down as follows: 59.3 percent federal, 20.4 percent from within

Dev. 3.5% Other* 3.8% academia, 6.6 percent from state/local government, 5.8 percent Nonproﬁts* 4.4% from industry and 7.8 percent from other sources (private foundations, charities, etc.). SOURCE: SEI 2012 Federal gov.

7.7% pursue internships and expand their nascent professional networks by all means possible. As China begins to train Applied research 21.9% more STEM degree holders than the U.S., from bachelor’s Academia* degrees to Ph.D.s (1), the U.S. must develop policies 13.6% Industry, aimed at attracting and keeping large numbers of high- funded by industry quality students on a scientifi c training and career path Basic research 60.6% over the next decade (4). 74.6% Industry, Whether you’re conversing with students, parents or U.S. senators, it’s important to build and reinforce your advice 9.9% federally funded and arguments with accurate data. Such information helps high school seniors make college choices, undergraduates select majors, graduates select areas of specialty and young scientists select career paths using rational logic. The 2012 SEI provides an excellent resource for understanding how STEM disciplines are impacting the U.S. economy and both decisions, even with some lingering college debt. I’ve being shaped by fi scal and societal forces. also recently written about weighing the costs and benefi ts As many of us know, the initial stages of new discov- of going to graduate school in the biosciences (3). eries are built upon the foundation of new knowledge attained through basic research. While industrial invest- Scientifi c training: the human ment in basic research is an important component, for the capital driving innovation past few decades federally funded academic investigators Well-trained human capital is vitally important for the have conceived and conducted most of the basic research sustained success of R&D initiatives in the U.S. Robust performed in the U.S (1). Although the majority of STEM economic growth that outlasts fi nancial-sector upheaval undergraduates, graduate students and postdoctoral fel- requires innovations that will be developed only if our lows ultimately will work outside of academia, during their highest-caliber students choose careers in R&D rather training they have the opportunity to participate in formulat- than fi nancial derivative packaging and sales. The route to ing and solving the motivating questions that will increase successful R&D careers includes undergraduate training our understanding of many important issues driving our with hands-on research experiences in STEM disciplines economy and transforming our society. and possibly additional graduate school (1). Careers in R&D pay higher median salaries and historically exhibit Michael J. Bradley ([email protected]) lower unemployment rates than other jobs that require at is a postdoctoral fellow in the department of molec- least a bachelor’s degree (1). Earning a STEM-discipline ular biophysics and biochemistry at Yale University. Ph.D. further increases the likelihood of landing and keeping R&D employment, along with even greater job security and a progressively higher wage distribution for many years after receiving the degree (1, 3). The majority of all referenCes 1. Science and Engineering Indicators 2012. www.nsf.gov/statistics/seind12/. STEM degree holders, including Ph.D.s, must ultimately 2. Surowiecki, J. The New Yorker. Published Feb. 14, 2011. Accessed March 11, 2012. develop careers outside of academia (1). Therefore it’s www.newyorker.com/talk/ﬁ nancial/2011/02/14/110214ta_talk_surowiecki. Bradley, M.J. . (August 2011). critical to advise students and mentees to consider sev- 3. ASBMB Today 4. Drew, C. The New York Times. Published Nov. 4, 2011. Accessed March 11, 2012. www.nytimes. eral career possibilities, conduct informational interviews, com/2011/11/06/education/edlife/why-science-majors-change-their-mind-its-just-so-darn-hard.html.

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READER COMMENTS ONLINE LETTER TO THE PRESIDENT response to the new mCat, President’s message, march 2012 march 2012 We’re pleased with Dear Suzanne, the dialogue that our I read your recent President’s Message t itled “Branch- recommendations gener- ing careers in biochemistry” in ASBMB Today with ated. ere is broad great interest. e issue around professional and career agreement on teaching development of biomedical trainees is one that is gaining molecular genetics in the more attention, and I enjoyed reading about the role year of premedical biol- the American Society for Biochemistry and Molecular ogy. Indeed, arguments Biology has taken. Sparked by your article, I thought you were made to exceed may be interested in hearing about additional opportuni- new MCAT standards ties for trainees occurring in the biomedical environment. in genetics and genomics. ere also has been Here in Alberta, Canada, Alberta Innovates-Health Solu- broad agreement that tions, the provincial funding body for health research and the MCAT core compe- innovation, also recognizes the importance of career and tencies in research methods and data analysis can be met by professional development for biomedical trainees along coursework in at least three di erent departments and that with the role mentorship plays in this process. AIHS two semesters of biochemistry should be recommended. We strongly supports the training of highly skilled academic are not surprised by the lively discussion of how to teach health researchers and also recognizes the need to provide chemistry to premedical students and are pleased to learn opportunities to those considering nonacademic careers. about Jonathan Clayden’s carbonyl- rst “Organic Chemistry” As such, our newly designed Graduate Studentships now textbook, I. David Reingold’s organic- rst approach at Juniata have a PLUS option associated with them, where the College, and Melanie M. Cooper and Michael W. Klymkows- funded trainee can access up to one additional year of ki’s year of life-oriented chemistry at University of Colorado. funding to gain valuable experience and additional skills ese courses and others to be developed can provide the beyond those acquired through their direct graduate general chemical rigor demanded by our critics, e ectively research training. is may include internships in policy, teaching chemical concepts with molecules found in living government, industry or not-for-pro t environments. It systems. CHARLES BRENNER, UNIVERSITY OF IOWA, is designed to allow trainees to tailor the PLUS experi- AND DAGMAR RINGE, BRANDEIS UNIVERSITY ence to their career goals. Also associated with all our Training and Early Career Development Opportunities is article has some good ideas, but item 2 is far too proscrip- is the requirement of a multifaceted mentorship advisory tive to receive the general cooperation of chemists who are committee. is committee may be similar to or di erent otherwise sympathetic to the recommendations. It does not from the trainee’s supervisory committee and includes even mention the Scienti c Foundations for Future Physicians his or her primary research supervisor; a co-mentor to document produced by the Howard Hughes Medical Institute provide an alternate perspective from another discipline, and (the) American Association of Medical Colleges. I and research focus, sector or institution; and a career mentor others are working with both the American Chemical Society to focus on the trainee’s career development. Committee on Education and the HHMI Nexus Experiment Grant to address these concerns. In particular, the one-year As an ASBMB member and scientist who has taken a chemistry part of recommendation, in my view, does not allow nonacademic career path, I am pleased to see ASBMB chemistry courses to adequately address the outcomes listed recognizes that scientists contribute in a variety of mean- in the SFFP document. I could have endorsed this if recom- ingful ways beyond the walls of academe. We should sup- mendation 2 were revised to [read,] “ e traditional sequence port and reward biomedical trainees whether their career of general and organic chemistry should be revised to a course paths are academic or otherwise. in life-oriented chemistry. ere are a variety of ways in which Kind t Regards, this goal could be achieved.” My views are my own and not Ryan Perr y intended to represent an o cial position of the ACS or HHMI. MARC LOUDON, PURDUE UNIVERSITY

34 ASBMB Today April 2012

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Of course, it is important to train students not just for the MCATs but also for medical college and beyond. e pro- Next month in ASBMB Today posed curriculum change will be very helpful in providing a In May, ASBMB Today science writer Rajendrani more uniform foundation of knowledge for incoming medical Mukhopadhyay profi les Robert Schimke, who once students. Teaching rst-year medical students is very chal- was president of the lenging when the class includes biochemistry majors alongside American Society people who have not taken any biochemistry. I am concerned, for Biochemistry and though, that one year of chemistry is not su cient, and I Molecular Biology and agree with Marc Loudon that the recommendation should be who served on the more exible to allow adequate coverage of these materials. editorial board of the FRED MAXFIELD, BIOCHEMISTRY, WEILL CORNELL Journal of Biological MEDICAL COLLEGE Chemistry. Schimke is As a practicing psychiatrist with a broad enthusiasm for known for major the sciences, I welcome these recommendations. Hard-core contributions to at organic chemistry is not in the working repertoire of any of the least four different doctors I see, though it was a tough hurdle in their training, areas of biology, and and it is a wonderful subject in its own right. e revised today he’s an artist. formulation suggests a much more relevant, lively line of study. I note that physics is not mentioned, though it forms the basis for a uni ed view of biochemistry. e medical students I meet are usually weak in this area. As far as “behavioral science,” I doubt that common psychology courses o er any richness compared to examined life experience or meaningful study of literature, sociology or anthropology. ese comments are solely my own. MICHAEL STITELMAN, YALE MEDICAL SCHOOL While I agree with Marc Loudon’s concerns about part 2 being quite proscriptive, I think that the ASBMB document is right on in regard to replacing much introductory organic chemistry with biochemistry (with a heavy emphasis on chemistry). As a biochemistry undergraduate (a long time ago) and a molecular biologist for many years, I am convinced that it must be possible to teach many organic chemistry principles What’s new in the context of biological molecules and thereby make orgo on Wild Types more interesting and useful for biology students. On the other here’s a snapshot of hand, I would have liked to see more discussion of the place asBmB today science of thermodynamics. But overall, I congratulate the ASBMB writer rajendrani mukho- committee with a report that should inspire tinkering in both padhyay’s blog. follow it at chemistry and biology departments. LASSE LINDAHL, wildtypes.wordpress.com. UNIVERSITY OF MARYLAND, BALTIMORE COUNTY • Khan Academy takes on biochemistry and molecular biology • Science funding through CORRECTION crowdsourcing • Leaf-cutter ants and their In the March 2012 issue of ASBMB Today, the article marvelous microbiomes “The men behind Western blotting” incorrectly referred • Wild Types: blogging to RNA or DNA blotting as immunoblotting. The about molecular biology, nucleic-acid detection methods don’t use antibodies biochemistry and anything in between! like Western blots. PHOTO: BANDWAGONMAN AT EN.WIKIPEDIA AT PHOTO: BANDWAGONMAN

April 2012 ASBMB Today 35

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