Vol. 13 / No. 4 / April 2014

The member magazine of The American Society For Biochemistry And Molecular Biology CONTENTS Best of JBC 2013: Podcast Series The Journal of Biological Chemistry has released a four-part podcast series to explore some of the research findings highlighted by the 2013 Best of JBC collection. The editors reviewed more than 4,000 articles published in NEWS FEATURES PERSPECTIVES 2013 and named 22 as the best, one article for each Affinity category. 2 32 40 PRESIDENT’S MESSAGE UNDER THE SPELL OF ESSAY Serendipity and ‘impact’ THE COCKROACH HUNTER ank God for overlapping genes

5 12 43 NEWS FROM THE HILL OPEN CHANNELS oughts on the proposed Petsko on the Ph.D. pipeline American Cures Act 6 40 MEMBER UPDATE 7 JOURNAL NEWS 12 RETROSPECTIVE 7 Part I: The N-terminal lobe regulating Argonaute slicer activity: Richard Hanson, 1935 – 2014 JBC’s best RNA article of 2013 With Rachel Green, Johns Hopkins University 14 LIPID NEWS

Part II: Prion-mediated toxicity of Aβ oligomers: 17 JBC’s best neurobiology article of 2013 NEWS With JBC Associate Editor Paul Fraser, University of Toronto; and Nigel Hooper, University of Leeds, U.K. 18 ANNUAL MEETING Part III: Key interactions at the HER2-HER3 kinase dimer interface: 18 How you can spread the good news JBC’s best signal transduction article of 2013 19 Your annual meeting checklist With JBC Associate Editor Alex Toker, Beth Israel Deaconess Medical Center; and Ron Bose, Washington University 20 Plan your meeting break time! 18 in St. Louis 21 Bringing science to San Diego 22 On the path to sustainability Part IV: α-synuclein, living cells and Parkinson’s disease: 23 Professional-development opportunities 24 Awards coverage JBC’s best cell biology article of 2013 With JBC Associate Editor Paul Fraser, University of Toronto; Dennis Selkoe, Harvard Medical School; and Ulf 32 24 Dettmer, Harvard Medical School In this month’s cover story, science writer Rajendrani Mukhopadhyay writes about To listen, visit www.jbc.org/site/podcast the jewel wasp, a fascinating parasite whose bewitching stings turn cockroaches into unwitting – and, simultaneously, willing – victims.

PHOTO BY VICTOR LANDA, UNIVERSITY OF CALIFORNIA, RIVERSIDE

APRIL 2014 ASBMB TODAY 1 PRESIDENT’S MESSAGE

berg was awarded the Nobel Prize in chemistry “for his studies of is misinterpretation of impact may be driving THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY the molecular basis of eukaryotic FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY Serendipity transcription” (5). is prize was research toward the middle of the clinical-fundamental primarily for the determination of continuum – that is, away from fundamental studies OFFICERS COUNCIL MEMBERS the three-dimensional structure of Jeremy M. Berg Squire J. Booker and ‘impact’ eukaryotic RNA polymerase. is toward translational ones, even if these are quite far President Brenda Schulman prize represents not a serendipitous removed from true clinical applications. Steven McKnight David Sabatini By Jeremy Berg discovery but rather the culmination President-Elect Melissa Starovasnik of many years of eort by Kornberg Karen Allen Wesley I. Sundquist of Nobel laureates for analysis clearly “impact” was not intended to mean Secretary and his co-workers on a well-recog- Gregory Gatto Jr. represents a highly selected group. short-term inuence on human Toni Antalis Natalie Ahn hen I was a young faculty favors only the prepared mind”). nized problem, namely the elucida- Treasurer With these caveats, the analysis health but rather the potential Anjana Rao member at Johns Hopkins Under ideal circumstances, scienti c tion of the structure and associated reveals that serendipity was the for changing the landscape of the Daniel Leahy W University, I served on the priority setting balances the bene ts mechanistic insights for a large and EX-OFFICIO MEMBERS Ph.D. thesis committee of Suzanne of exploring the unknown with its complex enzyme of central impor- primary driver in approximately 10 research elds involved, regardless Geeta Narlikar ASBMB TODAY Baker, a Ph.D. student in the labora- associated potential for truly novel tance to biochemistry and molecular percent of these accomplishments of whether these changes were close Enrique de la Cruz and a substantial contributor to an to a human health or clinical setting Co-chairs, 2014 Annual EDITORIAL ADVISORY tory of Bert Vogelstein, then an assis- discoveries against the selection of biology. Meeting Program BOARD tant professor in oncology. Baker’s problems that, if substantial progress An example of a hybrid discovery additional 25 percent. or were fundamental changes in Committee Charlie Brenner thesis project involved trying to iden- is made, will provide considerable is represented by the Nobel Prize to J. our understanding of basic biology. Peter J. Kennelly Chair Unfortunately, this broad perspective Chair, Education and Carol Shoulders tify a putative tumor-suppressor gene bene t to society. Michael Bishop and Harold Varmus Judging potential impact on potential impact sometimes has Professional Development Shiladitya Sengupta on human chromosome 17. Based in 1989 for their discovery “of the Committee e balance between selection of Yolanda Sanchez been lost during implementation, to Daniel Raben on considerable work mapping dele- Estimating the importance cellular origin of retroviral onco- important problems and the potential Floyd “Ski” Chilton some degree within the NIH but, in Chair, Meetings Committee tions in numerous human tumors, genes” (6). ey were working on a for unanticipated discoveries has been Cristy Gelling of serendipity my opinion, to a greater degree by Takita Felder Sumter she had reduced the search space to fundamental problem, namely the the topic of much discussion. Marc Peter J. Kennelly reviewers who interpret impact to Chair, Minority Aairs approximately one-fourth of the chro- Can we provide at least some bound- nature of cancer-causing genes from Kirschner of Harvard Medical School Committee Michael Bradley mean translational impact. Rajini Rao mosome. To put the nishing touch aries on the balance between seren- viruses. Identifying the nature of recently published an editorial in omas Baldwin is misinterpretation of impact Chair, Outreach Committee on Baker’s thesis, Vogelstein suggested dipity and problem importance? Sig- these genes, regardless of the answer, Science magazine titled “A Perverted may be driving research toward the Bob Matthews ASBMB TODAY that she sequence a gene that falls in ni cant discoveries can be primarily would have been of fundamental View of ‘Impact’” (7), in which he middle of the clinical-fundamental Chair, Public Aairs Angela Hopp the center of this region to rule out serendipitous; the result of incremen- importance. e answer turned out criticizes the use of “impact” and “sig- Advisory Committee continuum – that is, away from Editor, [email protected] this gene as the sought-after tumor tal, step-by-step solving of a known, to be of unanticipated signi cance, ni cance” as criteria in peer review Jerey Benovic Rajendrani Mukhopadhyay fundamental studies toward transla- Chair, Publications suppressor. e gene they selected important problem; or a hybrid of the revealing that the viral genes were by the National Institutes of Health. Sr. Science Writer, tional ones, even if these are quite far Committee [email protected] was p53, the product of which had two. An example of a largely seren- related to normal cellular genes that, I agree with Kirschner that the use removed from true clinical applica- Martha J. Fedor Marnay Harris been shown to associate with a key dipitous discovery was recognized when mutated in some ways, can of these terms has the potential to Editor-in-chief, JBC tions. Designer, [email protected] protein from the tumor virus SV40 by the Nobel Prize in physiology or contribute to cell transformation. distort judgments about the potential Herbert Tabor is middle region may, in fact, be Andrew Harmon (1). To everyone’s astonishment, medicine in 2006 to Andrew Fire and To look at the balance between consequences of supporting speci c Co-editor, JBC Science and Technology the least fertile area for real progress. Baker found point mutations in this Craig Mello for their discovery of serendipity and problem selection, proposals. However, as someone who A. L. Burlingame Publishing Manager, Fundamental research often turns Editor, MCP [email protected] gene in several tumors (2); they had “RNA interference-gene silencing by I examined all of the winners of was involved in the NIH “Enhancing out to be most inuential when it Edward A. Dennis Barbara Gordon stumbled on what turns out to be the double-stranded RNA” (4). the Nobel Prize in physiology or Peer Review” project (8) that led to Joseph L. Witztum Executive Director, is addressing basic biological pro- gene that is most commonly mutated is discovery was based on a medicine and chemistry over the the incorporation of these terms, I Co-editors, JLR [email protected] cesses of which our understanding in human cancer (3). chance observation made in the con- past 25 years and scored each win- can provide some context. is incomplete (i.e., most processes), While serendipity has been central text of studies of gene regulation in ner’s contribution as either largely First, what concerns about peer and important discoveries often are to a number of important discover- C. elegans wherein a control experi- serendipitous, largely driven by review led to the incorporation of made in model systems that are most ies, the importance of serendipity can ment involving the simultaneous solving a problem of known, fun- these terms? Much of the discussion amenable to controlled, detailed be overstated. e selection of the injection of both sense and anti-sense damental importance or a hybrid of with stakeholders both inside and study without regard to direct clinical problem under study is also essential, RNAs corresponding to the same the two. Of the 117 Nobel laureates outside of the NIH focused on the translation. In contrast, research at as is a deep knowledge of the eld in gene resulted in a dramatic change (as opposed to prizes, since in some fact that grant-application reviews For information on advertising, contact Fox Associates Inc. the clinical end of the continuum at 800-440-0231 or [email protected]. order to place incidental or unex- in gene expression not observed for cases individuals who shared a prize often were preoccupied with the often is most eective when a very pected ndings in perspective; the either the sense or anti-sense mol- fell into dierent categories), I clas- ne details of the scienti c approach well-de ned clinical context is pro- great microbiologist and biochemist ecules separately. eir appreciation rather than the proposed problem. si ed 14 as serendipitous discoveries, vided for the proposed study. Louis Pasteur famously said “Dans of this chance observation eventually Many indicated that they felt the 72 as driven by the importance of History has shown that many of www.asbmb.org/asbmbtoday les champs de l’observation le hasard revealed a widespread but largely potential importance of the problem the problem and 31 as hybrids. is the important applications of fun- ne favorise que les esprits prérparés” unsuspected biochemical pathway. classi cation is, of course, somewhat was receiving too little attention. (“In the elds of observation, chance In the same year, Roger Korn- subjective. Furthermore, the choice Second, the choice of the term CONTINUED ON PAGE 4

2 ASBMB TODAY APRIL 2014 APRIL 2014 ASBMB TODAY 3 NEWS FROM THE HILL

CONTINUED FROM PAGE 3 A balanced framework hands of the investigators involved)? (3) What are the chances that One of my former colleagues at the damental knowledge could not have something unanticipated will be been anticipated, and pushing appli- NIH (now retired) described to me Proposed American Cures Act discovered along the way? cants to propose such applications very succinctly what he felt he needed ese questions capture the can distort the basic research. Indeed, to make rational funding recommen- need to work on something impor- the National Institute of Neurological dations. He proposed three questions tant (with importance de ned in a is not a long-term solution Diseases and Stroke recently reported (which I have modi ed slightly): context-dependent manner) and an a detailed analysis that supported the (1) How important (either funda- integrated view of the approach and notion that applicants are moving mentally or in terms of applications) the skills and previous accomplish- away from truly fundamental research is the project if it is successful? to research-funding woes ments of the investigator(s) while to the detriment of the long-term (2) What are the chances that acknowledging the potential for mission of the institute (9). the project will be successful (in the By Benjamin Corb serendipitous discovery. I have found this to be a useful framework for REFERENCES guiding my own research planning, .S. Sen. Dick Durbin, D-Ill., National Science Foundation spe- analysts worry that funding the 1. http://p53.free.fr/p53_info/p53_disco.html and I hope you may as well. 2. http://www.ncbi.nlm.nih.gov/pubmed/2649981 recently sponsored a bill ci cally are not keeping pace with NIH through an alternative stream 3. http://www.sciencemag.org/content/339/6127/1546 U that would change how the those of our global competitors. It ultimately would reduce main-line 4.http://www.nobelprize.org/nobel_prizes/medicine/laureates/2006/ Jeremy Berg ([email protected]) is federal government funds biomedical should come as no surprise to many appropriations. Meaning, appropria- the associate senior vice-chancel- 5. http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2006/ research. Called the American Cures that, while the U.S. invests more in tors will see a trust fund in place and lor for science strategy and plan- 6. http://www.nobelprize.org/nobel_prizes/medicine/laureates/1989/ ning in the health sciences and Act, the bill would create a trust biomedical research than any other begin decreasing the base invest- 7. http://www.sciencemag.org/content/340/6138/1265.full.pdf a professor in the computational fund of sorts and mandate annual country (dollar for dollar), the gap ments in the NIH, guring that the 8. http://enhancing-peer-review.nih.gov/ and systems biology department increases in the research budgets for is closing as countries — includ- alternative funding will more than at the University of Pittsburgh. 9. http://blog.ninds.nih.gov the National Institutes of Health, the ing China, Singapore, Australia, adequately ll the coers. Should Centers for Disease Control and Pre- Germany and India — are invest- this happen, and, as many fear, vention, the Department of Defense ing increasingly larger percentages should the trust fund income be less health programs and Veterans Aairs of their gross domestic products in than expected, the NIH could end up at a rate of ination plus 5 percent. research than the U.S. is. in an even worse position than it is in e goal, it seems, is to put an end to e question, however, is how at the present. the repeated proposed increases for this proposed trust fund would be Durbin is an outspoken champion funding that do not even match ina- nanced and whether such a funding for biomedical research, and we all tion and have led to a loss of purchas- stream is a good idea. should commend him for his sup- ing power for a decade. e details about where Durbin port and his eort to nd creative e announcement came March plans to nd the money are sketchy at solutions to today’s research-funding 11 during a speech Durbin gave best. During his speech, he proposed problem. But the reality is that his at the Center for National Policy a nearly $1 increase in the tobacco plan does little more than put a in Washington. “In the last two tax and suggested that increase alone Band-Aid on a wound that needs to centuries, U.S. government support would cover half of the spending be stitched. for scienti c research has helped split needed to develop this new funding e appropriations process has the atom, defeat polio, conquer space, stream. But the source (or sources) of been hijacked by partisanship and create the Internet, map the human the other half remains unclear. near-sighted scal policies. e only genome and much more. No nation Plus, what happens when the real way to ensure reliable, long- has ever made such a signi cant funding streams dry up? Today, term investments in the NIH is to investment in science, and no nation’s segments of the CDC and the Food x the broken system by eliminating scientists have ever done more to and Drug Administration are funded unnecessary and damaging auster- improve the quality of life on Earth,” on similarly well-intended, but not ity measures (like the sequester and Durbin said. “But America’s place as completely reliable, alternative rev- discretionary spending cuts) and the world’s innovation leader is at risk enue sources, putting those budgets returning to the regular appropria- as we are falling behind in our invest- in peril. tions process. ment in biomedical research.” Finally, and perhaps most impor- Benjamin Corb (bcorb@asbmb. In many ways, Durbin is abso- tantly, what about unintended org) is director of public affairs lutely right. consequences? While supporters of at ASBMB. Research-funding levels in general the Durbin bill today are con dent and investments in the NIH and this wouldn’t happen, many policy

4 ASBMB TODAY APRIL 2014 APRIL 2014 ASBMB TODAY 5 MEMBER UPDATE JOURNAL NEWS

former editorial board member of the Journal of Biological Chemistry, Kinases control cytoskeleton Maxfield, Ory winners of NIH Clinical Center awards Magasanik had spent decades studying microbial physiology and response to cellular stress the regulation of gene expression. Upon learning of Magasanik’s death, By Mariana Figuera-Losada colleagues and former students recalled his storytelling ability and the Understanding the regulation of breadth of his knowledge. Magasanik cytoskeleton organization is fun- When cells are exposed to stresses, such as heat shock, was born in Ukraine in 1919. His damental for the control of cell family ed to Vienna after the division, migration, proliferation and osmotic or chemical stress, inammatory cytokines, Russian Revolution. Magasanik was MAXFIELD ORY dierentiation. Cytoskeleton dynam- proteasome inhibition and hypoxia, physiological studying chemistry at the University ics play a role both in physiological e National Institutes of Health last month announced that 10 groups of Vienna in1938 when Germany processes and in diseases such as responses promote the reorganization of the cytoskeleton of researchers will be granted access to the agency’s Clinical Center in annexed Austria and Jews were cancer. In their recent article in the to maintain structural integrity. Bethesda, Md. One group that won one of the three-year, renewable expelled from the universities. He Journal of Biological Chemis- grants includes two members of the American Society for Biochemistry immigrated to New York City, later try, Yan Y. Yip and colleagues at the and Molecular Biology: Frederick Max eld at Weill Cornell Medi- attending City College of New York. University of Melbourne revealed tubules. It can be phosphorylated in c-Jun N-terminal kinase, or JNK, cal College and Daniel Ory of the Washington University School of Drafted into the U.S. Army during new details about the complex signal- various serine residues in response and cAMP-dependent protein kinase, Medicine in St. Louis. While the NIH’s extramural funding supports World War II, Magasanik served in ing processes that determine cyto- to stress. ese post-translational or PKA. ese post-translational scientists beyond the agency’s walls, these awards are unique in that they medical units in England and France. skeleton reorganization in response modi cations reduce the stathmin- modi cations inhibit stathmin give the teams direct access to NIH’s resources. Max eld and Ory’s team He earned his Ph.D. from Columbia to cell stress. dependent inhibition of microtubule activity and preserve the integrity of will conduct a clinical trial on a drug against the most common form University in 1948 and joined the When cells are exposed to stresses, assembly, stabilizing microtubules microtubules. of Neimann−Pick disease, NPC1, a fatal, inherited lysosomal-storage Harvard Medical School faculty. In such as heat shock, osmotic or chem- and preserving cytoskeleton struc- ese researchers found by muta- disorder. e trial will be on the drug Vorinostat, a histone deacetylase 1960, Salvador Luria recruited ical stress, inammatory cytokines, ture. genesis that two residues, S38 and inhibitor that in early studies has show some promise in clearing cho- Magasanik to MIT, where he later led proteasome inhibition and hypoxia, e regulation of stathmin func- S63, are essential in the response to lesterol and other lipids from NPC1-mutant human cells. Max eld and the biology department, which almost physiological responses promote the tion through phosphorylation is hyperosmotic stress and required to Ory’s collaborators include Steven Walkley of Albert Einstein College of doubled in size during his tenure. reorganization of the cytoskeleton to a complicated process. Multisite fully attenuate the inhibitory eects Medicine of Yeshiva University and Forbes Porter of the Eunice Kennedy maintain structural integrity. phosphorylation occurs and dierent of stathmin. Shriver National Institute of Child Health and Human Development. An endowed professorship Microtubular cytoskeleton dynam- residues get modi ed depending on S38 is phosphorylated by for Hannun ics are in part determined by a small the cellular and signaling context. JNK early during the response to protein known as stathmin, or onco- e authors con rmed that hyperosmotic stress, followed by Yusuf A. Hannun, protein 18. Stathmin sequesters two stathmin gets phosphorylated dur- PKA-dependent S63 phosphoryla- AACR’s Pezcoller year, Fuchs was named as an inaugu- director of the tubulin dimers, destabilizing micro- ing hyperosmotic stress by tion. However, phosphorylation of ral fellow of the AACR Academy. Stony Brook fund award for Fuchs stathmin in position S63 did not She’s also a member of the National University Cancer Next month, Academy of Sciences, the Institute of Center, was require prior S38 phosphorylation. Elaine Fuchs of Medicine, the American Philosophi- granted an Additionally, the authors proposed the Rockefeller cal Society, the American Academy of HANNUN endowed profes- an interesting cross-talk between University will Arts and Sciences and the European sorship last month. Hannun’s JNK and PKA in which JNK could receive the 2014 National Academy of Sciences. investiture makes him only the eighth possibly be involved in the down- Pezcoller Founda- regulation of PKA activity during FUCHS endowed faculty member at the tion–AACR IN MEMORIAM: university, which has set its sights on hyperosmotic stress. International Award for Cancer at the having 100 within the next ve years. ese results highlight some of the American Association for Cancer Boris Magasanik Hannun’s endowed professorship, complexities of cytoskeleton regula- Research’s annual meeting in San Boris Magasanik established in 2001, is named after tion and the functional intercon- Diego. Fuchs, a Howard Hughes of the Massachu- Joel Strum Kenny, the late son of the nection between signaling pathways Medical Institute investigator, was setts Institute of university’s past president Shirley during cellular responses to stress. recognized for “her pioneering Technology died Strum Kenny. Joel Kenny, who died research on the biology of skin stem late last year at the of leukemia, had been a scholar, Mariana Figuera-Losada cells and how they go awry in human age of 94. A teacher and rabbi. Hannun is a past ([email protected]) is a MAGASANIK diseases of the skin, including longtime member winner of the American Society for This figure from the Yip et al. paper illustrates the contributions of specific stathmin serine residues postdoctoral fellow at the Johns cancer,” Margaret Foti, chief executive of the American Society for Biochem- Biochemistry and Molecular Biology’s phosphorylation to microtubule preservation during hyperosmotic stress (OS). Arrows point at cells with Hopkins University. ocer of the AACR, said. Just last istry and Molecular Biology and a Avanti Award in Lipids. destabilized microtubule cytoskeleton product of serine-to-alanine substitutions.

6 ASBMB TODAY APRIL 2014 APRIL 2014 ASBMB TODAY 7 Fast, cheap way to detect dyslipidemia genes Ptashne reflects on chemistry of gene regulation By Mary L. Chang By Jane Campanizzi

Researchers at the University of West- ing, the most widely used method to more information than those analyzed Mark Ptashne begins his “Reections” tein, not an RNA molecule and not ern Ontario have developed a new sequence DNA. by the Sanger method, which analyzed article in the Journal of Biological attached to one. ey showed that sequencing method to detect genes e authors report that there only three candidate hypercholesterol- Chemistry with a quote by French this protein could bind to speci c responsible for abnormal lipid levels potentially are several major bene ts to emia genes. biochemist and Nobel laureate DNA sites (operators) on DNA and in a variety of patients. using LipidSeq. e rst is speed: e While Johansen et al. admit Lip- Jacques Monod: “(T)he truth of a later showed that it could prevent Christopher T. Johansen and col- researchers analyzed 12 DNA samples idSeq detects more genetic variants theory lies in the deductive methods transcription of target genes. Ptashne leagues designed a targeted resequenc- in a week using LipidSeq, whereas it requiring investigation, they say that used to establish it and the experi- notes that the experiments showing ing panel, which they call LipidSeq, would have taken much longer with as more is learned about genomic vari- mental demonstration of its funda- that repressor binds DNA speci - that looks for genetic problems that Sanger sequencing. Second is overall ation in patients more insight will be mental premises and consequences.” cally and many other experiments can cause lipid abnormalities. In a cost: A LipidSeq sample costs about gained about the subtypes of dyslip- Ptashne’s article reviews and puts performed along the way demonstrate paper appearing in the April issue of half (less than $500) of what a com- idemia, and hopefully this will drive into context many of his experiments the power of combining genetics and the Journal of Lipid Research, parable sample for the Sanger method development of targeted therapies. on the molecular basis of gene regula- biochemistry. they report their results after using the would (around $1,000). Additionally, Mary L. Chang (mchang@asbmb. tion, beginning with bacteria and then By 1971, Ptashne was a professor. panel to look for responsible genes in the samples analyzed by LipidSeq were org) is publications manager for moving to yeast and mammalian cells. His lab’s next step was to determine 84 patients with lipid abnormalities analyzed for 23 dyslipidemia genes the Journal of Lipid Research. He emphasizes how, at each stage, how the repressor binds DNA. eir and comparing the results to those and 50 other metabolic genes – a alternative answers to problems were experiments, along with those of obtained by standard Sanger sequenc- targeted approach revealing much confronted and how key experiments others, indicated that an α helix (the distinguished between them. He also so-called recognition helix) at the emphasizes that the principles at work Mark Ptashne and his cat, McCoy repressor could insert into the major in bacteria apply as well in eukaryotes. groove of B-form DNA. Amino acid While an undergraduate at Reed regulation was the key. functional groups extending from the The invisible killer of research? College in Portland, Ore., in the e behavior of the bacteriophage helix would make speci c contacts By Shirley H. Tan 1960s, Ptashne rst learned of lambda, as pointed out by the French with base pairs. “dazzling ideas” emerging from the scientists, represented a paradigm. In But even repressor dimers, which Ever wonder why the results of cell ture, and consequently elicit numer- uorescence microscopy to measure Institute Pasteur in Paris. ere, a lysogenic bacterium, one repressor recognize sites of two-fold rotational culture experiments are sometimes ous protein modi cations that may two common autophagic markers, Monod and Francois Jacob, studying (the bacteriophage lambda repressor) symmetry, did not bind with su- dicult to replicate? A recent study lead to errant data interpretation. WIPI2 and LC3. After two hours gene regulation in bacteria, proposed keeps most of the virus’ nearly 40 cient speci city. Ptashne’s lab learned in the journal Molecular & Cel- e team tested the MCF7 breast of exposure to room-temperature that regulatory molecules called genes in a dormant state (o). UV that cooperativity is essential; one lular Proteomics may shed some cancer cell line in room temperature conditions, the number and size of “repressors,” Ptashne explains, “turn irradiation of these lysogens switches protein (e.g., a repressor dimer) helps lights on the secrets behind the com- and on ice and then monitored the the markers increased dramatically. o expression of speci c genes unless the regulatory program so that the another dimer bind DNA by merely plex biological mechanisms. changes by mass spectrometry. Nearly e protein assay also con rmed the inactivated by speci c extracellular silent genes are now on, and a new touching it. is simple binding Protein phosphorylation, a 1.5 percent of 3,500 phosphorylation increased phosphorylation of numer- signals.” crop of phage is produced. reaction, it turned out, also explains common type of post-translational sites measured were changed after ous other autophagy markers. Ptashne wanted to know: Was this Lambda was particularly interest- transcription activation by a speci c modi cation, plays critical roles leaving the cells in room temperature is study raises an interesting idea correct? What were “repressors,” ing to Ptashne and his colleagues DNA-binding protein: e “activa- in regulating signaling pathways for 15 minutes. In addition, while the question not frequently asked by the and how did they work? because it exempli ed the so-called tor” contacts RNA polymerase and involved in disease progression, eects were delayed compared with scienti c community: In 1962, Ptashne entered gradu- “memory” problem. Once lysogeny helps it bind and work at a promoter including cancers. With the advance- those in room temperature, maintain- Is it a real biology response, or is it ate school at Harvard University. was generated in a bacterium, he that lies near the activator binding ment of mass-spectrometry technol- ing cells on ice did not prevent the a response caused by sample retrieval? He writes that he and his colleagues writes, “that state of gene expression site. ogy, phosphoproteomics now enables cells from responding to metabolic e discoveries made by the were inspired by the dream that was perpetuated for very many gen- As Ptashne explains, a DNA- scientists to map in depth the delicate stress. e researchers found that Cutillas group provide another angle understanding “the repressor” would erations in the absence of an inducing bound activator recruits polymerase changes of protein biomarkers and ambient conditions at room tempera- from which to interpret research data “illuminate development of a com- signal. Neither ‘remembering’ nor to a promoter. e simplicity of allows them to interrogate impor- ture stimulated catabolic pathways more carefully. plex organism from a fertilized egg.” switching requires any mutation.” the activation mechanism means tant research questions. However, a involving AMPK and GSK3beta and By then it was strongly suspected Ptashne completed his Ph.D. in any gene can be brought under the team led by Pedro Casado and Pedro inactivated anabolic pathways regu- Shirley H. Tan that “formation of dierent body 1965, became a junior fellow of the control of any activator by apposing Cutillas at Barts Cancer Institute lated by AKT, ERK and mTOR. ([email protected]) is a parts requires dierential expression Society of Fellows at Harvard from the activator and polymerase bind- in London discovered that cells are Autophagy also was induced by the postdoctoral research fellow at of common genes, and that dierent 1965 to 1968 and started his own ing sites. And a suitably positioned extremely susceptible to environmen- environmental stress in this experi- Johns Hopkins School of Medicine. organisms can develop using essen- lab. ere, he and his colleagues tal stress stimuli, including tempera- ment. Cutillas’ team used immuno- tially the same set of genes.” And so isolated the repressor, a pure pro- CONTINUED ON PAGE 10

8 ASBMB TODAY APRIL 2014 APRIL 2014 ASBMB TODAY 9 CONTINUED FROM PAGE 9 working revealed only near the end. At every Talking about JBC’s Best of 2013 DNA-bound protein (e.g., lambda stage we could test this repressor) can turn o, or repress, or that aspect, challeng- In a podcast series, authors of four award-winning articles discuss their research certain genes as it activates others. ing with genetics and By Andrew Harmon e solution to the lambda mem- biochemistry, trying ory problem demonstrates that where to ensure that each bit To celebrate the articles the editors of assistant professor at Washington an activator works on its own gene, was well in hand before the Journal of Biological Chem- University in St. Louis. Bose’s article, that state of gene expression tends to going on.” He implies istry named the Best of 2013, the published in August, was selected self-perpetuate. As cells divide, the that today this is a rare journal has produced a podcast series from the JBC’s signal transduc- activator distributes to daughters, undertaking: “is featuring interviews with authors tion category. It provides the rst with the state maintained. Memory is approach is nowadays of four of the 22 articles that were structural characterization of HER2- thus a property of the system of basic rather out of fashion. honored. e series was launched in HER3 heterodimers, which are elements appropriately arranged. “By Instead we have the ‘big mid-February. In these interviews, part of the receptor family used in combining these elements, nature picture,’ many genes, authors oer personal insights into the development of targeted cancer can produce sophisticated switches, Lambda repressor and Cro action at the right operator (Or) in a lysogen obscure words and and following induction (bottom line). their work. therapies. Bose talks about his more which allows genes to be expressed formulations.” e rst podcast, posted in than 10 years of research in the study in alternate states, with sensitive and Ptashne then turned mid-February, features my interview of tyrosine kinases. He also talks dramatic transitions between them in cooperatively and in many dierent FOUR-PART SERIES his investigation to how the insights with Rachel Green, a professor at about where the research is going, response to signals,” he writes. combinations, turn on sets of genes. e following Journal of Bio- from the lambda work might apply Johns Hopkins University School of the development of innovation where Over the following years, Ptashne Some of these genes encode inhibi- logical Chemistry papers were to eukaryotes. He and his colleagues Medicine. She is the corresponding mass spectrometry is limited in the and colleagues described lambda’s tors that block the eects of activa- highlighted in the Best of JBC chose to work with yeast, a eukaryote author of the paper selected from the study of protein complexes that can’t switch as a complex set of interac- tors. Once positive feedback loops podcast series. Listen to them that could be genetically manipulated RNA category. Originally published be crystallized, and the power of tions that guaranteed expression of are established, they maintain states at www.jbc.org/site/podcast. almost as easily as bacteria. He writes in March 2013, Green’s article illus- interdisciplinary studies for graduate alternate sets of genes with a rapid of gene expression unless they are See other selected papers at that they “had no way of knowing, trates how, in gene regulation, rec- students in science. switch upon command. at the start, that studying λ repressor perturbed, such as by a signal, thus www.jbc.org/site/bestoftheyear. ognition of siRNA and microRNA In the nal podcast, we hear about e switch includes positive and permitting the system to move on and its action would yield a coherent structures by Argonaute proteins α to the next phase of gene expression. the debate surrounding -synuclein, RNA negative feedback; a double negative picture of a regulatory switch and inuences downstream eects on He speculates that the key is evolu- which plays a critical role in Parkin- Regulation of Argonaute Slicer circuit involving the repressor and even less indication that the principles target RNAs. She discusses the tion: “(S)election must occur in small son’s disease. Is it an unfolded mono- Activity by Guide RNA 3′ End the protein Cro; and cooperativity of protein-DNA interaction and gene way her article came about and the steps, and the simplest mechanism mer? Is it a helically folded tetramer? Interactions with the N-terminal of repressor binding, including the regulation, gleaned from the λ stud- direction she sees this research that works will be used over and over Associate Editor Fraser speaks with Lobe, by Hur et al. example (demonstrated later by oth- ies, would apply even in eukaryotes.” moving. again, sometimes in so many guises Dennis Selkoe at Harvard Institutes ers) of interactions between proteins ey showed, however, that In the second podcast, JBC NEUROBIOLOGY that the underlying similarities are at of Medicine and Ulf Dettmer, a separated by 3,000 base pairs, with eukaryotic activators (e.g., the yeast Associate Editor Paul Fraser at the Prion Protein-mediated Toxicity rst hard to see.” research fellow in neurology also at formation of a large DNA loop. protein Gal4) work, as does lambda University of Toronto speaks with of Amyloid-β Oligomers Requires Ptashne ends his “Reections” Harvard. Selkoe and Dettmer are A separate gene regulatory circuit repressor, as an activator – by recruit- Nigel Hooper at the University Lipid Rafts and the Transmem- by noting that “one can make ever co-authors of the chosen paper in establishes repressor synthesis in the ment. Only simple binding interac- of Leeds in the United Kingdom. brane LRP1, by Rushworth et al. broader generalizations by solving the cell biology category. Published rst place. As Ptashne notes, only tions are required, and it is thus easy Hooper is the author of the article basic problems, sometimes in near in March 2013, the article exhib- rather simple binding interactions are to see how “natural variation can selected from the neurobiology SIGNAL TRANSDUCTION fanatical detail, and then seeing where its a new method for cross-linking required to construct such a switch, throw up many regulatory-circuit category. Also published in March Carboxyl Group Footprinting those solutions can lead,” instead of α-synuclein in living cells that reveals and it is not hard to imagine how it options for natural selection to con- 2013, Hooper’s paper details how Mass Spectrometry and Molecular “looking at problems in general.” a form consistent with a tetramer. In might have evolved. ese aspects of sider.” remodeling amyloid-β oligomers and Dynamics Identify Key Interac- In addition, he writes, “No part of this conversation, we hear about the systems biology are widely found in e fact that eukaryotic genes are disrupting the prion-LRP1-raft inter- tions in the HER2-HER3 Recep- the world can simply be read – it prior research leading to this article gene regulatory circuits driving devel- wrapped in nucleosomes, whereas action can provide therapeutic targets tor Tyrosine Kinase Interface, by always must be interpreted, and those and what to look forward to as the opment of higher organisms. bacterial genes are not, presents a spe- for Alzheimer’s disease. Fraser and Collier et al. interpretations are subject to constant debate continues. Lambda “remains the best-under- cial problem for transcriptional activa- Hooper talk about the progression reevaluation.” You can nd links to play all four CELL BIOLOGY stood integrated system we have, and tors, and Ptashne recounts his group’s of this work and where the research podcasts at www.jbc.org/site/podcast. In Vivo Cross-linking Reveals perhaps one should ponder how we recent experiments that indicate the Jane Campanizzi (jcmtechser- may lead. Principally Oligomeric Forms of got it.” He writes, “e switch was way this problem is solved as well. [email protected]) is pursuing e third podcast features a con- graduate studies in the science- Andrew Harmon (aharmon@ α-Synuclein and β-Synuclein in not deduced from general observa- He observes that today diagrams versation between JBC Associate medical writing program at Johns asbmb.org) is the science and Neurons and Non-neural Cells, by tions or theoretical or mathematical of gene regulatory circuits look Hopkins University and serves Editor Alex Toker at Beth Israel publishing technology manager Dettmer et al. models. Its parts were assembled as like “a lot of lambdas” and that on the Publications Committee of the American Deaconess Medical Center and for the American Society for Bio- we went along, its glorious integrated regulatory proteins, usually working Medical Writers Association. Ron Bose, a medical oncologist and chemistry and Molecular Biology.

10 ASBMB TODAY APRIL 2014 APRIL 2014 ASBMB TODAY 11 RETROSPECTIVE

Richard Hanson, 1935 – 2014 By William C. Merrick, Vern L. Schramm and Michael A. Weiss

f we were to measure an individ- approached him for enlightenment, More than anyone at CWRU over ual by his dates on the earth, his none was turned away, and all left the past 36 years, Richard was about, I number of publications, his prizes with the feeling that they had a better as they say, improving the breed – both local and national, we would understanding and could go forward improving faculty (especially junior nd that Richard Hanson was a with whatever decision or choices faculty), the department, the medical model of success — and yet we would they had to make. He left a wake of school and the university. He was totally miss the value of the man. people aected positively by their recognized for that dedication with Richard was an accomplished interactions with him. the Hovorka Prize for university scientist who started his career at Although Richard had few down service and scholarly accomplishment Temple University and then in moments, the only true one he had and with a distinguished university 1978 moved to become chairman of was when he was informed that he professorship. Case Western Reserve University’s no longer would be teaching bio- Richard took advantage of his biochemistry department — the chemistry to medical students. e position as department chairman, gluconeogenesis house of kings estab- new curriculum was going to feature associate editor of the Journal of Bio- ing the banjo (obviously a Pete Seeger colleagues but included individuals lished by Merton Utter, the previous self-directed learning or problem- logical Chemistry and his presidency wannabe) and leading the department in the public eye as well, especially RICHARD HANSON chairman. Both Mert and Harland based learning and not lectures. After of the ASBMB to introduce CWRU in song (tunes we all knew, he said, the arts. SCHOLARSHIP FUND Wood were giants in the exploration polishing the delivery of metabolism faculty to the community of peer- which meant tunes from the ’60s Richard’s opinions were universally Checks payable to Case Western Reserve of the pathways of metabolism, Mert to thousands of medical students for reviewed science or the functioning and ’70s). Ken Neet and Dave sought for problems large and small. University should be sent to: in mammals and Harland in bac- more than 30 years and generating aspects of a scienti c society. Goldthwait (on accordion) would be He was the campus sage. But most Development and Alumni Aairs teria. Richard spent the rest of his life the most highly rated section of the e 1980s and 1990s often were lead vocalists in “On Top of Spa- of all, he generated a warm feeling in Case Western Reserve University studying the enzyme phosphoenol- preclinical curriculum, he was no referred to as the golden years in the ghetti” and “Alouette,” respectively. everyone he met. His conversations School of Medicine pyruvate carboxy kinase, or PEPCK, longer to be a participant. medical school as department chair- is past December’s was the only were characterized by his blue eyes 10900 Euclid Avenue the rate-limiting enzyme in gluconeo- Although Richard continued men Les Webster, Mike Lamb, Fritz Winter Solstice party that Richard and dimples, the easy laughter, the Cleveland, OH 44106-7035 gensis, and establishing the cAMP- teaching undergraduates, the medical Rottman and Richard presented a did not attend. It was a party that quiet concern. Please include a memo: dependent regulatory mechanism that students were his true love. ere uni ed force for the improvement of he, though perhaps a not-ready-for- Another quality of Richard’s was Richard Hanson Endowment Fund controlled PEPCK mRNA synthesis. was always the 70-kilogram man or the school. eir cooperation led to prime-time performer, wouldn’t miss. that he didn’t have to be right. Any Who would have thought you could 50-kilogram woman upon whom all the establishment of the Reinberger Many of Richard’s talents were discussion entered was about opin- SEIDMAN CANCER CENTER become so famous studying just one the reference numbers for metabolism Laboratories, the correlated curricu- widely recognized. His banjo play- ions and facts and how they might be Checks payable to University enzyme, even when it gave rise to were based, and Richard would select lum in cell and molecular biology ing was well known throughout the best interpreted, understood or used Hospitals should be sent to: Mighty Mouse (the PEPCK-Cmus such a student from each rst-year (lecture and laboratory), and the medical school and, alas, throughout as a place to move forward from. It University Hospitals mouse that could run forever)? class. What was the longest a medical Biomedical Sciences Training Pro- his home. His doodles, known aec- was not personal that he didn’t agree Institutional Relations But far greater were his contribu- student had fasted? Is the Atkins diet gram, an umbrella program to tionately as “Riccasos,” are featured with you or you with him; it was just and Development tions to the university; the American a good idea? Why is the woman on recruit Ph. D. students into all of in a gallery in the biochemistry about interpretation. As a result of 11100 Euclid Ave. Society for Biochemistry and Molecu- the pineapple diet not feeling well? the departments of the medical MCCO 5062 department and as a set of note cards this honesty, there was never a ques- Cleveland, OH 44106 lar Biology; his beloved Journal of When students would return years school. prepared by the ASBMB. Richard tion of his motives, never a question Biological Chemistry; and his col- later, while they remembered the But what Richard really cherished Please include a memo: also supported the Cleveland artistic about the truth of his statements, in memory of Dr. Richard Hanson leagues, students and friends. preclinical years as being challenging, were his interactions with others. community as seen through count- never a question about his leadership. Richard was the best representa- the one teacher they remembered was e biochemistry department’s less acquisitions he made, which are His transparency provided a secure tion of a modern renaissance man, a Richard – out of the hundreds they Winter Solstice party was a highlight. displayed in the department. calm in which his department, his William C. Merrick ([email protected]) is a scholar who was knowledgeable about had seen. e sparkling blues eyes Richard was a prominent character e phrase often associated with collaborators and his colleagues could professor in the biochemistry department at Case science, art, music, literature, govern- and truths delivered with humor and in the faculty skit (when the heat’s Will Rogers was that “he never met operate and ourish. Everyone left Western Reserve University. Vern L. Schramm ([email protected]) is chairman of ing and life in general. And perhaps clarity motivated generations and on, the ham sizzles). He praised the a man he didn’t like.” For Richard, better for the interaction, and per- in spite of that knowledge base, served as a model of engagement to delicious dishes representing many the biochemistry department at Albert Einstein the phrase might be “he never met haps this is for what he will be most College of Medicine of Yeshiva University. Michael Richard was the eternal optimist: e his teaching cohorts. He thrived on tastes and heritages the department an individual he couldn’t say some- measurably missed. He was a most A. Weiss ([email protected]) is chairman of the glass was always at least two-thirds his interactions with students. members brought to the feast. thing positive about.” And this was wonderful human being who made biochemistry department at Case Western Reserve University. full. Of the countless visitors who And it was not all about Richard. Richard found great joy from play- not restricted to just his scienti c all of us better.

12 ASBMB TODAY APRIL 2014 APRIL 2014 ASBMB TODAY 13 LIPID NEWS Organization of glycolipid A physicist’s view of the role biosynthetic enzymes of lipids in membrane in the Golgi complex curvature and fission By Hugo J.F. Maccioni By Patricia Bassereau

lycolipids play diverse bio- transmembrane Proximal Golgi he de nition of lipid rafts has logical roles – from serving as domain anked by Gal-T1 Sial-T1 Sial-T2 evolved considerably over the Another interesting aspect ... is that lipid domains in G receptors of toxins and growth a short cytoplas- GlcCer GlcCer LacCer GM3 GD3 T past 15 years. ey now are rec- factors to overseeing molecular mic tail and a ex- ognized as dynamic “nanoscale assem- membrane accompany a constrictive force acting at the recognition at the cell surface. ese ible lumenal stem BFA blies of sphingolipids, cholesterol and periphery of the domains, the line tension, resulting molecules are composed of a ceramide region to which a proteins that can be stabilized into Distal Golgi (TGN) backbone to which monosaccharide large C-terminal platforms” (1) and no longer viewed from the nonmiscibility of the dierent phases. Sial-T1 Sial-T2 (sugar) molecules are attached. e domain bearing LacCer GM3 GD3 as static microdomains (2). Confu- order in which dierent sugars are the sugar nucleo- GalNAc-T sion occurred because of the dierent meter range by setting membrane for redistributing the lipids than the attached to the ceramide backbone is tide and acceptor GM2 GD2 methods used to reveal and character- tension, dierent groups of physicists membrane shape only, as they can a crucial feature in determining the glycolipid binding Gal-T2 ize the lipid rafts and in part because quantitatively assessed the conditions amplify (8, 9) or completely reverse precise role of a glycolipid. Under- sites is appended GM1 GD1b of the unfortunate concomitant and the eciency of this lipid-sorting (11) curvature-induced lipid sort- standing the machinery that regulates (reviewed in 2). Sial-T4 revival of membrane physics, which process (7 – 9). An enrichment in ing, depending on the anity of the the glycosylation of the ceramide Notably, the GM1a GD1b was boosted by the possibility of membrane nanotube in unsaturated protein for curved membrane. (For backbone, therefore, is critical to our GGTs are unlike observing phase separation in giant phosphatidylcholine, or PC, lipids as reviews on these questions, see refer- understanding of the biosynthesis of glycoprotein gly- Plasma Membrane unilamellar vesicles, or GUVs, with compared to sphingomyelin was mea- ences 12 through 14.) these important lipids and provides cosyltransferases, confocal microscopy (3, 4). sured (8), and it was shown to result Another interesting aspect revealed insight into the mechanisms underly- which alternate A simplified scheme of ganglioside biosynthesis, showing the topological Physics studies with reconstituted from the reduction of the energy used by membrane physicists, both theo- ing diseases resulting from aberra- with glycosidases distribution of the GGT in Golgi compartments as deduced from the block imposed simple lipid mixtures generally were by Brefeldin A (marked gray) in metabolic labeling studies with CHO-K1 cells. to bend the membrane. retically and with their model systems, tions of their synthesis. Interestingly, in the process- made at equilibrium, whereas cell Indeed, PC-rich membranes are is that lipid domains in membrane the organization of the glycosylation ing of oligosaccharides, in that they have demonstrated interesting dier- lipid membranes are clearly not. more exible than those enriched in accompany a constrictive force act- machinery within the Golgi is linked are not strictly distributed along the ences in the organization of speci c Nevertheless, the interplay between sphingomyelin (8). However, this ing at the periphery of the domains, intimately to the supramolecular orga- Golgi in the order in which they act. GGTs. cell biology and membrane phys- eect was not detected for arbitrary the line tension, resulting from the nization and dynamics of the Golgi Instead, they organize as distinct For example, in CHO-K1 cells, the ics inspired other physics studies, in mixtures, and proximity to lipid nonmiscibility of the dierent phases. complex itself. homo- and hetero-multienzyme com- N-terminal domains of GalT1, SialT1 particular investigations into the role demixing, and hence lipid-lipid e energy relative to line tension e enzymes responsible for plexes, which in many cases involve and SialT2 (see gure) participate in that membrane curvature plays in interactions, were critical for observ- is proportional to the perimeter of catalyzing the stepwise addition of their N-terminal domains (3). a heterocomplex in the Golgi and the sorting lipids. It was suggested, based ing sorting (7 – 9); otherwise, the the domain; thus, by reducing the monosaccharides to ceramide and Deducing the sub-Golgi localiza- trans-Golgi network, while the com- on in vivo observations of uorescent mechanical gain is too small and domain contour length, line ten- ceramide-bound oligosaccharides are tion and organization of GGTs has plex formed by GalNAcT and GalT2 lipid homologs, that lipids could be completely dominated by the mixing sion can induce the bending of the the glycolipid glycosyltransferases, been challenging. Our current under- localizes instead in the trans-Golgi redistributed upon budding due to entropy of the lipids. domains in moderately tensed GUVs or GGTs (reviewed in 1). Research- standing results mainly from studies network (5). Recent studies in FAPP2 the high curvature of the membrane Observation of macroscopic lipid (4) and even squeeze the bud down to ers have given considerable eort to involving activity determinations in knockout mice reveal that the synthe- (5, 6). domains on giant plasma membrane scission (unpublished data). Squeezing understanding the organization of Golgi subfractions, cell metabolic sis of Gb3 in the TGN uses LacCer e development of new in vitro vesicles blebbing from cells (10) sug- of membrane nanotubes also occurs GGTs within the Golgi. labeling in the presence of pharma- synthesized from GlcCer transported systems was crucial to understand and gests that this membrane could be, at when lipid domains are present and Like other Golgi glycosyltrans- cological reagents that disrupt Golgi by nonvesicular (FAPP2) intermedi- quantify the corresponding sorting equilibrium, close to demixing and can lead to their spontaneous scission ferases, GGTs that use GlcCer and dynamics and structure like Brefeldin ates, while the track for synthesis mechanisms. Using membrane nano- that this sorting mechanism might be even in the absence of any protein (7). more complex glycolipids as acceptors A, single-cell imaging, and immu- of GM3 in the Golgi uses LacCer tubes pulled from GUVs made of relevant at this level in cells. Neverthe- A combination of in vitro and in show a modular organization, with noprecipitation of epitope-tagged simple lipid mixtures and controlling less, interactions between lipids and their N-terminal domain bearing a versions (reviewed in 4). Such studies CONTINUED ON PAGE 16 their radius in the 10 to100 nano- proteins probably are more ecient CONTINUED ON PAGE 16

14 ASBMB TODAY APRIL 2014 APRIL 2014 ASBMB TODAY 15 NEWS

CONTINUED FROM PAGE 14 An interaction of amino-acid brane domains of Golgi and plasma- synthesized from GlcCer transported motifs at GGTs’ cytoplasmic tails with membrane-resident proteins (the yeast by vesicular intermediates (6). coat proteins has been proposed to SNAREs Sft1 and Sso1, respectively) Public-private initiative aims GGT organization, however, is mediate retention in yeast (7). Addi- showed that, in addition to the short only part of the story. How GGTs and tionally, it has been suggested that a length, the presence of voluminous Golgi-resident proteins are main- hydrophobic mismatch between the amino acids in the exoplasmic hemi- short TMDs of some glycosyltransfer- TMD is a crucial parameter for Golgi to speed drug development tained in the Golgi while plasma- membrane-destined proteins exit the ases and the increased bilayer thick- localization. Proteins with longer Golgi remains a mystery. Bioinformat- ness of Golgi membranes at export TMDs and less voluminous exoplas- ics data indicate that transmembrane domains, due to the addition of mic halves exit the Golgi and localize for three illnesses domains, or TMDs, of Golgi proteins order-inducing sphingolipids and cho- to the plasma membrane both in yeast (which represent about 80 percent of lesterol and/or to the concentration of and in mammalian cells (10). e NIH, industry and nonpro ts announce Accelerating Medicines putative glycosyltransferases) are four proteins with long TMDs, segregate ese studies highlight the role of the shape of TMDs in the tness of to ve amino acids shorter than those them from these domains (8). Partnership focused on Alzheimer’s, diabetes and autoimmune disorders glycosyltransferases (or their oligo- of plasma-membrane proteins (9, 10), Studies using chimeric proteins meric associations) in either proces- but the signi cance of this to GGT have provided some hints on this By Sapeckshita Agrawal sive or export lipid domains of Golgi organization is unclear. point. Swapping the hemi-transmem- membranes. Clearly, we are learning a lot about t takes several years and millions years for research REFERENCES the localization and topology of these of dollars for a new drug to come aimed at identifying Accelerating Medicines Partnership participants 1. Yu, R.K. et al. J. Lipid Res. 45, 783 – 793 (2004). important enzymes. But the story is I to market, starting from the time biological targets Government Industry Nonprofits 2.Varki, A. et al. Essentials of Glycobiology. 2nd edition. Cold Spring Harbor Laboratory Press (2009). far from complete. Studies like these, that its properties are rst studied at and characterizing FDA AbbVie Alliance for Lupus Research 3. Giraudo, C.G. et al. Proc. Natl. Acad. Sci. USA. 98, 1625 – 1630 (2001). as well as others intended to enhance the bench. at’s a lot of time and new biomarkers. e NIH Biogen Idec Alzheimer’s Association 4. Maccioni, H.J. et al. FEBS Lett. 585, 1691 – 1698 (2011). our understanding of these enzymes, money. What’s even more stupefying parties have agreed Bristol-Myers Squibb American Diabetes Association 5. Ferrari, M.L. et al. Neurochem. Res. 37, 1325 – 1334 (2012). will keep the glycolipid community is that only a fraction of drug can- unanimously to make GlaxoSmithKline Lupus Foundation of America 6. D’Angelo, G. et al. Nature 501, 116 – 120 (2013). busy for a long time. didates make it to market. Clearly, a the resulting data 7. Tu, L. et al. Science 321, 404 – 407 (2008). new approach to drug development is and analyses publicly Johnson & Johnson Lupus Research Institute 8. Bretscher, M.S. & Munro, S. Science 261, 1280 – 1281 (1993). Hugo J.F. Maccioni ([email protected]) is needed – one that not only expedites available despite Lilly Foundation for the NIH 9. Sharpe, H.J. et al. Cell 142, 158 – 169 (2010). a professor emeritus at the National University of Merck Geoffrey Beene Foundation Córdoba in Argentina. and increases the availability of drugs conventionally being 10. Quiroga, R. et al. J. Cell. Sci. 126, 5344 – 5349 (2013). but also maintains the high standard competitors. e Pfizer PhRMA of quality needed to ensure safety and expected conse- Sanofi Rheumatology Research Foundation eciency. quence is the stitch- Takeda USAgainstAlzheimer’s LIPID NEWS CONTINUED A new collaboration announced ing together of a vast earlier this year called the Accelerat- knowledge network made by the milestone-driven pilot CONTINUED FROM PAGE 15 ing Medicines Partnership seems to needed to solve the big problems of projects in the three disease areas. promise a viable solution. e col- pharmaceutical research. vivo experiments now demonstrate Capturing the spirit of the col- laborators include 10 of the world’s Mikael Dolsten, president of that this squeezing eect can occur REFERENCES laboration, Rupert Vessey of Merck leading pharmaceutical companies, worldwide research and development during membrane budding if lipid 1. Simons, K. & Gerl, M.J. Nat. Rev. Mol. Cell. Biol. 11, 688 – 699 (2010). said, “Our most critical health chal- the National Institutes of Health at P zer, a participant of AMP, opti- heterogeneities form induced by actin 2. Simons, K. & Toomre, D. Nat. Rev. Mol. Cell. Biol. 1, 31 – 39 (2000). lenges require new, innovative ways and several nonpro ts. e goal: to mistically prognosticated that “this laments (15). is might be the case 3. Bagatolli, L.A. & Gratton, E. Biophys. J. 78, 290 – 305 (2000). to develop medicines and vaccines. develop new treatments earlier for type of novel collaboration will lever- also upon BAR-protein assembling at 4. Baumgart, T. et al. Nature 425, 821 – 824 (2003). Collaborations such as this, that three serious conditions – Alzheimer’s age the strengths of both industry and the neck of the bud (16, 17). 5. Mukherjee, S. & Max eld, F.R. Trac 1, 203 – 211 (2000). exchange data, share insights and disease, type 2 diabetes and autoim- NIH to ensure we expedite transla- In conclusion, lipids can give a 6. van Meer, G. & Lisman, Q. J. Biol. Chem. 277, 25855 – 25858 (2002). generate knowledge, will be impor- hand to specialized proteins to pro- 7. Roux, A. et al. EMBO J. 24, 1537 – 1545 (2005). mune disorders, namely rheumatoid tion of scienti c knowledge into tant to unraveling the mysteries of duce forces that remodel membranes. 8. Sorre, B. et al. Proc. Natl. Acad. Sci. USA 106, 5622 – 5626 (2009). arthritis and lupus. next-generation therapies to address the diseases that cause suering for But, conversely, when membranes get 9. Tian, A. & Baumgart, T. Biophys. J 96. 2676 – 2688 (2009). “Patients and their caregivers are the urgent needs” of patients. individuals and are a burden to our deformed by coats, cytoskeleton or 10. Lingwood, D. et al. Proc. Natl. Acad. Sci. USA 105, 10005 – 10010 (2008). relying on science to nd better and e research will be overseen by society.” molecular motors, lipids and proteins 11. Safouane, M. et al. Trac 11, 1519 – 1529 (2010). faster ways to detect and treat disease steering committees with representa- 12. Callan-Jones, A. et al. Cold Spring Harb. Perspect. Biol. 3, a004648 (2011). and improve their quality of life,” tion from both the public and private Sapeck Agrawal (sapeck.sriv- can be relocalized because of shape [email protected]) earned her 13. Callan-Jones, A. & Bassereau, P. Curr. Opin. Solid. St. M. 17, 143 – 150 (2013). changes in the membrane matrix. NIH Director Francis S. Collins said sectors. Oering even more hope to Ph.D. in molecular microbiology 14. Baumgart, T. et al. Annu. Rev. Phys. Chem. 62, 483 – 506 (2011). in the announcement. patients and families is the possibility and immunology from the Johns Patricia Bassereau (patricia.bassereau@curie. 15. Römer W, et al. Cell 140, 540 – 553 (2010). e syndicate has pledged more of extending AMP to other diseases Hopkins University. For more fr) is a group leader in the physical chemistry 16. Liu, J. et al. Proc. Natl. Acad. Sci. USA 103, 10277 – 10282 (2006). than $230 million over the next ve and conditions through advances stories, visit sapeckagrawal.wordpress.com. division of the Curie Institute in Paris. 17. Zhao, H. et al. Cell Reports 4, 1213 – 1223 (2013).

16 ASBMB TODAY APRIL 2014 APRIL 2014 ASBMB TODAY 17 MEETING

How you can spread the good news Your annual meeting checklist We need your help with getting the word out Be prepared for meeting highlights, and avoid meeting fails By Angela Hopp By Shaila Kotadia

Experimental Biology 2014 is just Start your meeting experience [email protected] by April 15, our 1. Download the meeting app. phone. And they seem to all need to you’re at it, throw in some Band-Aids around the corner, so it’s time to right by joining ASBMB sta to learn media relations team will include it in It is great to browse on your ight and be charged at the same time. Remem- just in case. start thinking about how you’ll Twitter tips and tricks to use during the materials issued to reporters who plan your schedule, especially now ber to bring a charger for each. For communicate your science and the the annual meeting and beyond. We visit the on-site press room. that program booklets are not sent international participants, bring a 8. Bring an extra pair of pants. science presented by others in San welcome a group of diverse profes- prior to the meeting. Find the app converter! ose are not easy to nd OK, boys. I know most of you travel Diego. sionals from a variety of areas includ- Plan on blogging while soon at www.experimentalbiology.org. at the last minute. with one pair of pants and then you ing academia, nonpro ts, industry, get caught in the rain or some other at the meeting? Don’t forget to use media, etc. Attendees will leave the 2. Hang onto your poster! 5. Pack a notebook and pen. disaster. Just bring an extra pair, espe- the hashtag! breakfast informed, equipped and Last but certainly not least, we’re tak- Yes, you have your glossy poster It seems old-school but they’re handy cially if you are going to meet col- caeinated. ing applications from members who ready to go, but what if you acci- when perusing posters, taking notes leagues — even if they are scientists. If you plan to tweet at the annual are interested in serving as ocial dentally leave it at airport security at talks or quickly writing down meeting, please use the #xBio Don’t be afraid to do meeting bloggers. e American because that lady behind you rushed someone’s contact info. It is also way 9. Remember pain killers hashtag. Additionally, if you tag Society for Biochemistry and Molecu- you along because she decided to lighter than carrying around a laptop and other meds. a little of your own PR @ASBMB in your tweet, we’ll do lar Biology will cover your meeting show up 20 minutes before her or tablet all day. Seriously, talking to scientists all day our best to retweet you to our follow- You still have time to work with your registration fee, and you’ll gain entry ight? Be sure to pack your poster can give anyone a headache, and you ers. If you’re on Instagram, we’ll be institution’s media relations oce to the press room (read: free food printed out on sheets of paper as a 6. Nonacademic careers are know those little packets of two at looking for #xBio-tagged images and on a press release about the research and wi ) and access to the scienti c backup. Carry the handouts with all the rage these days. the hotel cost as much as the whole will include them in post-meeting you’ll be sharing at the meeting. A sessions of all six EB-sponsoring you in case you need to explain your If you are looking to branch out bottle back home. For those of you collections. If you follow us on couple of years ago, ASBMB Today societies. Ocial meeting bloggers work on the y. from the lab, business cards are a with bad allergies, bring extra pills. Facebook, you can check there for published a handy guide for starting may write on their own blogs or on must when networking. Nothing too New environments can produce some posts about big events each day. the media-outreach process. You can ASBMB’s ocial meeting blog, e 3. Have your data nicely fancy — just your name, job title and adverse eects. Not a fan of our page yet? Like us nd it at http://bit.ly/zQghRK. We Interactome. e deadline for appli- organized on your laptop. contact info. Adding your poster or strongly recommend that you work at www.facebook.com/asbmb. cations is April 15. Contact Angela If you bring your computer to show talk title and presentation number 10. Importantly, bring your I.D. with your institution to generate press Hopp at [email protected] if you’re o your data, have it labeled and eas- makes it easy for others to nd you You want to get on the airplane. interest in your ndings. Reporters Join us for #breakfast interested. ily accessible. You don’t want to make later or to view your work. Enough said. these days don’t have time to wade Angela Hopp ([email protected]) someone wait while you look around When: 7 a.m. to 8:15 a.m. Sunday, through the thousands of abstracts to is editor of ASBMB Today. in your folders. It gets awkward really 7. Give your feet a break. April 27 nd you, so do them and yourself a quickly. We all want to look good, but Where: San Diego Convention Shaila Kotadia (skotadia@asbmb. favor and reach out to them. If you heeled or tight shoes can be hard on Center, Room 14A (Mezzanine Level) send a copy of your press release to org) is an ASBMB science policy 4. Get your devices ready. the knees or feet after a full day of fellow. For some reason, I need to travel conferencing. Pack a pair or two of with my laptop, tablet and cell (stylish) comfortable shoes. While

18 ASBMB TODAY APRIL 2014 APRIL 2014 ASBMB TODAY 19 Plan your meeting break time! Bringing science to San Diego By Shaila Kotadia By Geo Hunt

While the science presented at the Lounge? beach receives many votes for the best e American Society for Biochem- Communication workshop ence? Do you just want a break from American Society for Biochemistry If a pub is more your style, try e beach. istry and Molecular Biology annual posters and lectures? If you answered “You Can’t Say at on Television and Molecular Biology annual meet- Field. • Tourmaline: Always wanted to meeting once again will feature a yes to any of these questions, then (or to Congress, or to Students)” ing is bigger and better than ever, And if none of these sounds like try to surf? is break has a calmer full slate of programming from the join us for our annual EB science there is always down time. And part of your scene, that’s OK. ere are wave, making it a good spot for Public Outreach Committee. If you When: 12:30 p.m. Monday, April 28 café, which will take place in the heart the fun of a conference is traveling and plenty of other bars just around the beginners. is will require renting a are interested in getting involved with Where: San Diego Convention of the San Diego Gaslamp District. checking out a new city. So why not corner. board and wetsuit, and an instructor outreach or just curious about what Center, Room 14A, Mezzanine Level UNESCO has designated 2014 take a break and explore San Diego? will make a huge dierence, especially outreach is, come check out one of Eective public outreach relies on as the Year of Crystallography to Whether you’re looking for family- Tired of the food if this is your rst time out. Also, be our events. your ability to communicate about celebrate 100 years of X-ray dirac- tion with the goal to “increase public friendly spots or places where you at the convention center? sure to check when the surf is good, science with a wide variety of audi- can let loose, San Diego oers plenty because no waves means no sur ng. Outreach poster session ences in a plethora of dierent for- awareness of the science of crystallog- of options. Here are some places and e restaurant Searsucker gets top ose who want to watch surfers, raphy” (3). e ASBMB is getting in When: after the opening lecture Satur- mats and venues. With that in mind, events to check out: billing on Yelp and features main rather than doing the sur ng, and the spirit by hosting a public science day, April 26 we’ve put together a workshop that courses from the ocean, farm and those more experienced surfers should will train you on how to do just that. café on protein structure. Where: San Diego Marriott Marquis, Are you traveling with ranch. e French Café Chloe check out Oceanside and Ocean A roomful of communication e café will focus on FoldIt (4), Marriott Hall 3, North Tower an interactive game developed by family and children? provides a more intimate space. For Beach. Both have piers with good experts will help you tailor your those of you on a budget, San Diego views. And those looking for more To get things rolling, we will host research description for dierent David Baker and his lab at the Uni- versity of Washington. Users play the e famous San Diego Zoo boasts is known for its sh tacos. Be sure to advanced adventures can take the a special outreach-themed poster ses- stakeholders, including the media, game by using amino-acid sequences animals ranging from condors to ask around for the best. You’re bound long walk from the Torrey Pines area sion after the opening lecture on the K – 12 students and policymakers. and general rules of protein folding to giant pandas to wombats. A one- to get several suggestions. to discover Black’s Beach. night of Saturday, April 26. Posters Bring your poster or talk abstract solve complex protein structures. Lab day pass for an adult is $46 and for Finally, for vegetarians, try out an will showcase various outreach and and get expert feedback and advice member Brian Koepnick will lead a a child (aged 3 to 11) is $36 and ethnic option like Pokez Mexican Want a special event informal science-education programs on how to ensure that your message hands-on demonstration of the game includes a guided bus tour, access to Restaurant or Royal India. (ese from around the country. resonates with your audience. never to forget? at this event, showing how players the circulating Kangaroo Express bus, oer lots of meat options as well.) Examples include Trainee Meet- e workshop will serve as an ings Outside the Box (1), a graduate- from any background can participate, access to the Skyfari aerial tram and In addition to the relationships you introduction to several science- student-run mentorship and science- potentially even ending up as co- the entry fees for any ongoing shows. Want to check out build and the science you learn at the communication programs that we communication program at the authors on scienti c publications (as Other family-friendly venues conference, you can make lifelong are developing. You can register at the Pacific shore? University of Texas Health Science happened in 2011 for a group work- include Sea World ($84 for adults memories by attending a local event. http://bit.ly/P5YHyM. and $78 for children) and Legoland San Diego is known for its beauti- It is even better if you attend with new Center in San Antonio (1), as well as ing on folding algorithms) (5). ($83 for adults and $73 for children). ful beaches. e water probably will friends you meet at the conference! the ASBMB Undergraduate Aliate

not be warm enough to swim in, but e Adams Avenue Unplugged Network chapter at San Francisco Science café Opportunities for outreach Looking for a good lying in the sand and checking out Festival takes place once a year State University, which will highlight “Game Changer — How a Com- at every turn the gorgeous waves will be well worth on Adams Avenue in the Normal its collaborations (2) with Bay puter Game Can Turn You into a time out? it. If you’re lucky, you may spot some Heights neighborhood. e music Area Science Festival and Guerilla Real-Life Hero” We hope that those of you attending the annual meeting will interact with e Gaslamp Quarter is the place to ocean wildlife — seals, dolphins and festival hosts more than 100 acts in Science, a collective that combines When: 7:30 p.m. Monday, April 28 science with cultural activities. Take the nonscientist attendees, because, go out for dinner and drinks — and maybe even a whale! local establishments. e neighbor- Where: Southpaw Social Club, 815 J. this opportunity to chat with your in our opinion, the best way to get dancing and shows. And it is just a Below are just a few in a long list hood also oers an array of restau- St., San Diego, Calif. 92101 few steps away from the San Diego nearby beaches. Be sure to ask locals rant, bars, coee shops, art galleries fellow scientists about their experi- involved with outreach is to get Are you a protein biochemist? Do Convention Center, where the meet- for their favorite spots. and antique shops. is year the ences and see for yourself how out- involved with outreach. you like communicating with people ing will be held. • Mission Beach: e most well- festival will be Saturday, April 26, and reach is getting done at the ground So once you get your ll of science about the joys and wonders of sci- e weather is bound to be gor- known beach in San Diego, Mis- Sunday, April 27. level. at the meeting, come to our sessions geous, so check out a rooftop bar. Get sion has a famous boardwalk and is to see how you can do a little bit more. We’ll see you out in San Diego. a fantastic view at the ALTITUDE attached to Belmont Park, where the Shaila Kotadia (skotadia@asbmb. REFERENCES Sky Lounge. Giant Dipper roller-coaster resides. org) is an ASBMB science policy 1. http://research.uthscsa.edu/opa/t-mob.asp Geoff Hunt ([email protected]) Not into rooftops? How about an • Coronado Beach: is beach fellow. 2. http://www.asbmb.org/asbmbtoday/201401/EnlightenmentParty/ is the ASBMB’s public outreach underground bar with no cover and is loved by the locals and by tourists 3. http://iycr2014.org/ manager. a good dance scene like e Red C for its vast beauty. Year after year, this 4. http://fold.it/portal/ 5. Khatib, F. et al., Proc. of the Natl. Acad. of Sciences USA 47, 18949 – 18953 (2011).

20 ASBMB TODAY APRIL 2014 APRIL 2014 ASBMB TODAY 21 On the path to sustainability Addressing the problems of an unbalanced research enterprise By Chris Pickett

ese are stressful times for biochem- more ecient cooperation among the ogy Licensing Oce, Lita Nelsen ists and molecular biologists. Funding academia, government and industry has extensive experience overcom- which has been stagnant for some stakeholders and setting the entire ing barriers between academia and time — took a signi cant hit last enterprise on a path to predictable industry to enable the movement of year when sequestration kicked in. increases in funding. technology and expertise between Funding levels have yet to recover. But how can this vision be imple- the two. And Paula Stephan, author e available faculty positions for up- mented in times of government aus- of “How Economics Shapes Science” and-coming scientists are few and far terity and signi cant regulatory and and Science Careers’ 2012 Person of between, and formal job training for cultural roadblocks to interactions the Year, is an economist who brings careers away from the bench can be among the stakeholders? e second an outsider’s view of the strengths and hard to come by. Interactions and col- stage of the PAAC’s sustainability weaknesses of the scienti c enterprise. laborations among academia, govern- initiative will explore this question at We want to hear from you, the ment and industry are often strained the Experimental Biology meeting in meeting attendees, as well. is is due to the very dierent cultural goals April in San Diego. A panel session why we have reserved half of the and needs of each stakeholder. Inef- on the second day of the meeting will 90-minute session for the panel to cient and ineective collaborations address the barriers to sustainability interact with the audience to hear among stakeholders, the potential of and discuss possible mechanisms your ideas and questions about build- continued poor funding and a lost to overcome these impediments. ing a sustainable biomedical research generation of scientists threaten the Sitting on this panel will be four enterprise. In addition, an informal underlying stability of the American distinguished guests with experience mixer will follow the session for biomedical research enterprise. bridging the divides among academia, panel participants, audience members To address this threat, the Public government and industry: and PAAC members to mingle and Aairs Advisory Committee of the Lana Skirboll has a unique per- continue discussions about this very American Society for Biochemistry spective on industry and government, important topic. and Molecular Biology has launched as she worked on science policy issues With the biomedical research a project with a goal of moving the for more than two decades at the enterprise so far o balance, the biomedical research enterprise onto National Institutes of Health before PAAC panel session at the Experi- a sustainable path. e rst stage of becoming the vice-president of aca- mental Biology meeting surely will this project, as discussed by ASBMB demic and scienti c aairs at Sano . generate some lively discussion. We President Jeremy Berg in August, Michael Marletta serves as the presi- hope to see you there! was to draft a white paper outlin- dent and chief executive ocer of e ing a vision for this enterprise. is Scripps Research Institute, and he Chris Pickett (cpickett@asbmb. vision included improving education has a rm understanding of industry org) is a policy analyst at ASBMB. opportunities for trainees to prepare through his own startup ventures. them for the variety of careers avail- As the director of the Massachu- able; providing a new framework for setts Institute of Technology Technol-

22 ASBMB TODAY APRIL 2014 APRIL 2014 ASBMB TODAY 23 ANNUAL AWARDS

In this issue: In the March issue: 24 Ruth Kirschstein Diversity in Science Award winners Alice and C.C. Wang Award in Molecular Parasitology Freeman A. Hrabowski III and Michael F. Summers winner Ken Stuart 26 Herbert A. Sober Lectureship winner Dana Carroll ASBMB/Merck Award winner Benjamin Cravatt Walter A. Shaw Young Investigator in Lipid Research 27 ASBMB Award for Exemplary Contributions to Education winner Mary Kraft winner Harold B. White III Mildred Cohn Award in Biological Chemistry 28 Bert and Natalie Vallee Award in Biomedical Science winner Lila Gierasch winner Michael M. Gottesman Avanti Award in Lipids winner Sandra Hofmann 29 ASBMB-Howard K. Schachman Public Service Award ASBMB Young Investigator Award winner Samie R. Jaffrey 30 William C. Rose Award winner Lynne Maquat DeLano Award for Computational Biosciences winner Michael Levitt 31 Herbert Tabor Research Award winner Bruce Stillman Earl and Thressa Stadtman Scholar Award winner Aviv Regev

RUTH KIRSCHSTEIN DIVERSITY IN SCIENCE AWARD this, Summers has mentored several postdocs and high-school students in his lab. Hrabowski and Summers recognized Hrabowski earned an M.A. in mathematics and a Ph.D. in higher for their support of underrepresented minorities education administration and statistics By Anna Shipman from University of Illinois at Urbana– Champaign. In 2012, Hrabowski e American Society for Biochem- results of the program. student in the program, worked with was named one of the Top 100 Most istry and Molecular Biology has “e Meyerho program is one of Summers to create a model of one of Inuential People in the World by named Freeman Hrabowski III and the best programs in the country for the proteins that makes up HIV, a Time Magazine and was named as Michael Summers the winners of developing undergraduates for future model of which was featured on the chair of the President’s Advisory Com- mission on Educational Excellence the Ruth Kirschstein Diversity in scienti c training, including students cover of e Journal of Molecular It has been a tremendous privilege I am honored to be receiving this for African-Americans. Hrabowski’s Science Award. e award recognizes from groups that are underrepresented Biology in 1994. Summers’ most to work with Freeman for the past award with my colleague Mike research primarily focuses on sci- outstanding scientists who show a in science,” says Jeremy M. Berg, the recent paper on HIV-1 genome pack- 25 years on activities that are so Summers. His passion for science ence and math education, especially strong commitment to mentoring and ASBMB’s president and the associate aging, published in Science, included important to science and society. and for supporting students inspires minority involvement. Hrabowski encouraging underrepresented minori- senior vice-chancellor for science strat- 10 undergraduate co-authors. I am especially proud to be a me every day. e Meyerho Pro- ties to enter the sciences. egy and planning at the University of Summers has designed and directs gave a TED Talk in 2013 in which he member of ASBMB, an organiza- gram and UMBC’s other diversity Hrabowski, president of the Pittsburgh. “Part of the power of the both graduate and undergraduate shared some of the approaches used at tion that has played major roles in initiatives have been successful University of Maryland, Baltimore program is the deep involvement of training programs at UMBC. e UMBC to help more students from helping ensure that science educa- because our culture emphasizes high County, cofounded the Meyerho outstanding research scientists who Doctoral Diversity program supports all backgrounds succeed in science tion and science careers are broadly expectations, hard work and support Scholars Program in 1988 with provide tremendous research opportu- underrepresented minorities in Ph.D. and math. accessible. for all. Like Mike, faculty and sta philanthropist Robert Meyerho. e nities for undergraduates.” programs in biomedical sciences there Summers earned his B.S. in – MICHAEL SUMMERS are committed to inclusive excellence. program’s goal is to help underrep- As a Howard Hughes Medical Insti- and at the University of Maryland– chemistry from the University of West – FREEMAN A. HRABOWSKI III resented minorities pursue advanced tute investigator at UMBC, Summers Baltimore. is program is considered Florida and a Ph.D. in bioinorganic degrees and research careers in science has collaborated with the Meyerho a model due to the high retention chemistry from Emory University in graduate school and then to their and engineering. Since 1993, there Scholars Program by mentoring a large rates and increased enrollment of in Atlanta. Summers has been an own independent careers,” says Berg. have been more than 800 gradu- number of students in the program. minorities into Ph.D. programs. HHMI investigator since 1994 and is Hrabowski and Summers will ates from the program, and most e research focus of his lab is the use At the undergraduate level, Sum- a distinguished university professor of receive the award during the 2014 Anna Shipman (alsnpc@mail. have earned or are working toward of nuclear magnetic resonance and mers mentors UMBC students as chemistry at UMBC. umkc.edu) received her B.S. in ASBMB annual meeting in San biology–biotechnology from Mis- graduate or professional degrees. e other biophysical methods to examine part of the HHMI Biological Sciences “Mike Summers has built an abso- Diego, where Summers will give a lec- souri Western State University and program has been lauded as a national RNA structural elements involved in Training Program and non-UMBC lutely world-class research program ture. e presentation will take place is a Ph.D. student in the School of model, and Hrabowski has published the genome packaging of viruses. students in the Summer Biomedi- primarily around undergraduate stu- at 9:05 a.m. April 28 in Room 6A of Biological Sciences at the University of Missouri– Kansas City. several articles and books based on the Chianna Paschall, a chemistry cal Training Program. In addition to dents, many of whom have continued the San Diego Convention Center.

24 ASBMB TODAY APRIL 2014 APRIL 2014 ASBMB TODAY 25 HERBERT A. SOBER LECTURESHIP ASBMB AWARD FOR EXEMPLARY CONTRIBUTIONS TO EDUCATION Carroll acknowledged for his work White called ‘one of the most interesting, on genome editing with targetable nucleases engaging and genuine individuals’ By Kyeorda Kemp By Shaila Kotadia

Dana Carroll, professor of biochem- genes for deletion and modi cation Harold B. White III, professor of bio- engaging and genuine individuals to istry at the University of Utah School in a number of organisms. chemistry and director of the Howard ever grace a biochemistry classroom of Medicine, has won the 2014 Her- In a 2010 interview with the Hughes Medical Institute Under- full of rapt students.” bert A. Sober Lectureship award from corporate publication Biowire, graduate Science Education Program Prior to devoting his career to the American Society for Biochemis- Carroll stated, “People can now at the University of Delaware, is the undergraduate education, White try and Molecular Biology. contemplate making very speci c winner of this year’s American Society researched the structure, function and Carroll, whose early scienti c mutations in their genes of interest, for Biochemistry and Molecular Biol- evolution of vitamin-binding proteins interests were in the physical sciences, which was only previously possible in ogy Award for Exemplary Contribu- and was an early advocate of the won the Sober lectureship for devel- yeast and some simple organisms, and tions to Education. “RNA World” hypothesis, publishing oping the use of zinc- nger nucleases in mice. With ZFN technology, this e annual award is granted to more than 100 papers on these and as reagents for making site-speci c targeting capability is available for a scientist who excels in leadership, other subjects. White has had nearly double-strand breaks in the chromo- lots of dierent organisms. So that’s writing, research, mentoring or public 80 undergraduate research students in somes of living cells. ese reagents been a big change for geneticists, but engagement to teach biochemistry his laboratory over the years. Kathleen have allowed researchers to make the eld is still expanding. e num- is award has special meaning for and molecular biology eectively. Cornely at Providence College noted, I thank the students and colleagues who nominated me for this award targeted genome modi cations in a ber of applications is still increasing me because Herb Sober was a family “Hal is a consummate teacher “About one-fourth of the undergradu- that recognizes my eorts to promote wide range of organisms. as we learn more about how we can friend as I was growing up. In addi- whose inuence on his students goes ate students in Hal’s lab appear as co- and use problem-based learning in “Gene-targeting procedures have use them.” tion to people in my laboratory and well beyond the classroom. Indeed, authors on research papers resulting undergraduate education. Receiving been available for fungi and for Indeed, phase I clinical trials are my collaborators, I am grateful to many of his undergraduate students from the work of his group.” the many researchers around the this award is humbling because there mouse (embryonic stem) cells for under way using ZFNs as a treatment report that he has directly aected White started out as a curious world who have taken the basic are so many other biochemistry and many years, but the absolute frequen- for HIV, and preclinical studies using their career choices,” said Judith Voet undergraduate majoring in biochemis- targeting technology, improved it molecular biology educators worthy cies of targeted modi cation were these procedures to treat animal mod- of Swarthmore College and Donald try at the Pennsylvania State Uni- and applied it in ways I had not of the honor. us I see my recogni- low, and the approaches were not els of human diseases have proved Voet of the University of Pennsylvania versity, where he conducted under- imagined. It’s been a lot of fun. tion as symbolic of the eorts of all applicable to other organisms,” says successful, indicating that there is in their nomination of White for the graduate research and was elected to – DANA CARROLL educators whose passion is rewarded Carroll’s colleague Martin Rech- potential for this technology to be award. honor societies in chemistry, biology by the enthusiasm of their students steiner. “Carroll’s insight was that used for gene therapy. White’s dedication to serving and mathematics. His research career who accept intellectual challenges the genomic target is essentially inert “It is my opinion that textbooks of Carroll, who has received a num- students is exempli ed by his having began in earnest during his graduate and glow when their eorts are re- for recombination and that double- biochemistry and molecular biology ber of awards and accolades over his been a program director with HHMI studies in biochemistry at Brandeis warded with deeper understanding. strand breaks in the target DNA will will place Dr. Carroll’s development career, including the 2012 Novitski funding since 1998. He, with col- University. He then took a postdoc- – HAROLD B. WHITE III substantially stimulate the process. of zinc nger nucleases as tools for Prize from the Genetics Society of leagues, has received numerous grants toral research fellowship in chemistry He then sought DNA cleavage genome editing alongside Sal Luria’s America and an American Cancer to implement the problem-based at Harvard University with Konrad reagents that could cut at speci c, and Ham Smith’s work on restriction Society Scholar in Research Award, approach to learning. He is also a Bloch, a 1964 Nobel Prize winner and was elected a fellow of the American but arbitrarily chosen, sites.” — namely in the class of fundamental will receive his Sober award from co-founder of the Institute for Trans- 44th president of the ASBMB. White Association for the Advancement of Carroll rst showed the ability of discoveries that have indelibly altered the ASBMB during the Experimen- forming Undergraduate Education at has been at the University of Delaware Science. zinc nger nucleases to make germ- academic, industrial and medical tal Biology 2014 conference in San the university. ere, professors from since 1971. He will receive his award at the line modi cations in the Drosophila biotechnology,” says Philip D. Diego. His award lecture will take colleges and universities attend work- White has received multiple awards 2014 ASBMB annual meeting in San melanogaster genome, and his lab Gregory, chief scienti c ocer and place at 9 a.m. Wednesday, April 30, shops that use problem-based learning for his eorts, including the Univer- Diego, where he will give a presenta- generated targeted mutagenesis and vice president for research at San- in Room 6A of the San Diego Con- to teach undergraduates how to solve sity of Delaware College of Arts and tion. e presentation will take place gene replacement in the germline gamo BioSciences Inc. vention Center. complex problems that connect to Sciences 2005 award for outstand- at 12:30 p.m. Sunday, April 27, in in more than 10 percent of cases in Carroll earned his bachelor’s real-world issues. ing teaching and its 2007 award for Room 6A of the San Diego Conven- this organism. e lab also has used degree at Swarthmore College and his White also spends a signi cant outstanding service, and the 2011 tion Center. this approach in nematodes, plants Ph.D. at the University of California, amount of time in the classroom. Howard Barrows Award for excep- Kyeorda Kemp (kkemp134@ and silkworms. Other nucleases that Berkeley. He also completed postdoc- Marilee Benore at the University of tional undergraduate teaching from Shaila Kotadia (skotadia@asbmb. gmail.com) will be starting as an org) is an ASBMB science policy target the genome have been devel- toral stints at the Beatson Institute for assistant professor of biology at Michigan at Dearborn, a former grad- McMaster University. He was named fellow. oped based on this approach, and this Cancer Research and at the Carnegie Northeastern State University in uate student in White’s lab, said, “Hal the 2013 CASE–Carnegie Delaware technology is being used to target Institution of Washington. the fall. White is one of the most interesting, Professor of the Year and recently

26 ASBMB TODAY APRIL 2014 APRIL 2014 ASBMB TODAY 27 BERT AND NATALIE VALLEE AWARD IN BIOMEDICAL SCIENCE ASBMB-HOWARD K. SCHACHMAN PUBLIC SERVICE AWARD Gottesman recognized for his accomplishments Rice University undergrad called in multidrug resistance in cancer ‘champion of science education’ By Natalie Osayande By Shaila Kotadia

Michael M. Gottesman, deputy direc- director recruited Gottesman to head Zack Kopplin, science-education ally as a political activist) taught him tor for intramural research at the up the intramural research program, advocate, is the winner of the Ameri- the power of using his voice to eect National Institutes for Health, is the says that he knew at the time of Got- can Society for Biochemistry and change. us, Kopplin used his voice inaugural winner of the American tesman’s integrity, scholarship and Molecular Biology’s 2014 Howard K. to raise concerns about the act. “All Society for Biochemistry and Molecu- reputation but that he was “astounded Schachman Public Service Award. the Louisiana Science Education Act lar Biology’s Bert and Natalie Vallee by the quality of his leadership, the e award recognizes an individual does is create an unconstitutional Award in Biomedical Science. soundness of his judgments and the who demonstrates dedication to pub- loophole to sneak the teaching of e award was established by the energies he brought to the task of lic service in support of biomedical creationism or intelligent design in Bert and N. Kuggie Vallee Founda- running the (intramural program) in science as exempli ed by the award’s public school science classes,” he said. tion in 2012 to recognize established the more than 20 years since then.” namesake, who served as chairman of After writing a research paper on scientists with outstanding accom- Gottesman’s concern and impact the ASBMB’s Public Aairs Advisory the act for an English class, Kopplin plishments in basic biomedical on trainees also makes him a suit- Committee from 1989 to 2000. launched a campaign to repeal the research. Gottesman’s research focuses able candidate for this award, says e award, instituted in 2001, is act. ough the law was not over- primarily on multidrug resistance in Samelson, chief of the Laboratory I am deeply honored to be the rst given annually by the society’s Public turned, Kopplin did succeed in rally- It’s a huge honor to receive this recipient of the Bert and Natalie award. I’m thrilled to be coming to cancer, which is the main impedi- of Cellular and Molecular Biology Aairs Advisory Committee. ing students and scientists through- Vallee Award in Biomedical Sci- D.C. to help remind Congress that ment to successful chemotherapy. at the Center for Cancer Research. Jeremy Berg, president of the out the country, including 78 Nobel ence. Bert Vallee was a pioneer in science funding and education must Lawrence E. Samelson at the Echoing that sentiment, Paul A. Insel ASBMB and director of the Uni- laureates, in his campaign. metalloenzyme characterization and not be politicized. National Cancer Institute, who nomi- at the University of California, San versity of Pittsburgh’s Institute for Now 20 years old, Kopplin contin- a mentor to many successful scien- – ZACK KOPPLIN nated Gottesman for the award, says: Diego, says: “Michael has been a Personalized Medicine, said, “Zack ues to speak out against the teaching tists. rough their foundation, he “For nearly three decades, Dr. Gottes- leader in education and the training has been a true champion of science of creationism, often appearing on and his wife Natalie (Kuggie) were man has made seminal contributions of scientists: For example, he estab- education, which has become all such shows as HBO’s “Real Time ing eorts to protect the integrity of generous supporters of innovative to the understanding of multidrug lished the Undergraduate Scholarship science education.” and interactive science and scientists. the more important in these times with Bill Maher” and MSNBC’s resistance in cancer cells, through the Program, the NIH Academy, and the where educational standards are being “Hardball with Chris Matthews.” Kopplin has received multiple – MICHAEL M. GOTTESMAN use of a variety of approaches and Clinical Research Training Program. debated. Zack has tirelessly fought for Kopplin also wrote an open letter to awards for his eorts as a science- techniques involving biochemistry, He has consistently been a voice for the teaching of evolution in class- President Obama, saying, “Deny- education advocate, including the cell biology and molecular genetics. data-driven studies that inuence the studying molecular genetics with rooms.” ing and misteaching evidence-based Friends of Darwin Award and the (His) work has resulted in a new eld research and training environments in Martin Gellert at the NIH, joined the As a high-school student, Kop- science like evolution and climate sci- Hugh M. Hefner First Amendment of study of ATP-dependent transport- biomedical science in the U.S.” Harvard faculty and returned to the plin, a native of Baton Rouge, La., ence will confuse our students about Award in education. Kopplin received ers, has advanced the eld of molecu- Insel also noted that Gottesman NIH, where he has held several posi- was infuriated to learn that the 2008 the nature of science and stie future the Schachman Award at an ASBMB lar diagnosis of multidrug resistance, also has had many editorial responsi- tions. Today, while serving as deputy Louisiana Science Education Act had American scientists and scienti c Public Aairs Advisory Committee has contributed to a new understand- bilities for e Journal of Cell Biol- director for intramural research, he passed. e act allows supplemental innovation.” reception on April 1 in Washington, ing of the pharmacokinetics of most ogy, Molecular Cancer erapeutics heads up the Laboratory of Cell Biol- teaching materials to be used to cri- Benjamin Corb, director of public D.C. drugs in common use, and promises and Molecular Pharmacology and has ogy at the National Cancer Institute. tique or objectively review scienti c aairs for the ASBMB, said, “Zack to lead to new approaches to the still maintained a very active and suc- Gottesman will receive his award theories. Kopplin’s upbringing with is an impressive young advocate for Shaila Kotadia (skotadia@asbmb. treatment of drug-resistant cancers.” cessful research program. during the Experimental Biology a political inuence (his father was science. He exempli es how his gen- org) is an ASBMB science policy Gottesman and co-workers cloned “Michael has been a star for his 2014 conference in San Diego, where the former chief of sta to Louisiana eration can begin a larger discussion fellow. the gene encoding the rst-known entire career,” says Insel. he will deliver an award lecture. e governors Mike Foster and Kathleen on issues important to the teaching of mammalian ATP-dependent trans- Gottesman graduated from presentation will take place at 8:30 Blanco and was recognized nation- science. We applaud Zack’s continu- porter and described the mechanism Harvard College with a bachelor’s a.m. Sunday, April 27, in Room 6A by which it confers multidrug resis- in biochemical sciences and earned of the San Diego Convention Center. tance. He was rst to propose that his medical degree from Harvard Natalie Osayande (natalie. multidrug transporters recognize sub- Medical School, where he trained in [email protected]) is an strates while in the plasma membrane Bert Vallee’s lab. After his residency undergraduate at the University of and expel them from the cell. at the Peter Bent Brigham Hospital Tampa studying biochemistry. Harold Varmus, who as NIH in Boston, he did a postdoctoral stint

28 ASBMB TODAY APRIL 2014 APRIL 2014 ASBMB TODAY 29 WILLIAM C. ROSE AWARD HERBERT TABOR RESEARCH AWARD Maquat, ‘a pioneer in the field of mRNA regulation’ Stillman recognized for significant By Shaila Kotadia research accomplishments toward is year’s winner of the American the eld of mRNA regulation, and Society for Biochemistry and Molecu- she has continued to make seminal better understanding DNA replication lar Biology William C. Rose award is contributions to this eld ever since.” By Natalie Osayande Lynne Maquat, director of University Maquat joined the faculty at of Rochester’s Center for RNA Biol- Roswell Park Cancer Research, the Bruce Stillman, president of Cold assembly are molecularly linked. ogy and professor in the biochemistry oldest cancer center in the U.S., Spring Harbor Laboratory and direc- Stephen Bell, professor of biol- and biophysics department. before moving to her current profes- tor of the the CSHL Cancer Center, ogy at the Massachusetts Institute of Established more than three sorship at the University of Rochester. is the winner of the American Society Technology, a Howard Hughes Medi- decades ago and named after a former During her tenure as a professor, for Biochemistry and Molecular Biol- cal Institute investigator and a former president of the American Society she has trained a large number of ogy’s Herbert Tabor Research Award. postdoctoral fellow at Stillman’s lab, of Biological Chemists, ASBMB’s graduate-student and postdoctoral e award recognizes scientists whose said that Stillman has led the eld of precursor, the Rose award recog- researchers who’ve had a great deal excellent research has made major eukaryotic DNA replication into “new nizes outstanding contributions to of success when moving on to their impacts on the eld and the scienti c important directions.” Stillman’s dis- biochemical and molecular biological own laboratories. Olaf Isken, one is is an honor to be shared with many others. I feel very privileged to community. coveries have helped scientists better research and a demonstrated com- of Maquat’s former postdoctoral As a researcher, Stillman has made understand diseases, including cancer. mitment to the training of younger researchers, said that Maquat “showed have worked with so many talented graduate students and postdocs, foundational discoveries that contrib- His discoveries also have encouraged scientists. to me a remarkable commitment to uted greatly to our understanding of research in the elds of DNA repair Maquat began her career as an promote my professional career.” As without whom my lab’s research ac- I am thrilled by this major recogni- complishments would not have been DNA replication, and as director and and eukaryotic genomic stability. undergraduate at the University of the founder and chair of the Univer- president of CSHL for the past 20 “Bruce has also been a generous tion from ASBMB of contributions Connecticut Storrs Campus and sity of Rochester Graduate Women possible. When I mentor others, I made together with many talented do so with gratitude for those who years, he has nurtured and developed citizen of science,” said Anindya continued on to the University of in Science Program, Maquat is also a students and postdoctoral fellows made my research career possible outstanding programs in cancer, Dutta, a former postdoctoral fellow Wisconsin–Madison, where she mentor beyond her lab. in guring out how our genome is – supportive professors when I was molecular biology, neuroscience, plant in Stillman’s lab and currently the earned a Ph.D. in biochemistry. She In light of her many achievements inherited. younger and supportive colleagues, biology and genetics/genomics. chair of biochemistry and molecular remained at UW–Madison for a and commitment to research and – BRUCE STILLMAN friends and family after I started my Nobel laureate James Watson, who genetics at the University of Virginia, postdoctoral fellowship in molecu- mentorship, Maquat is an inspira- own lab. nominated Stillman for the award, noting that Stillman has trained many lar biology and human disease at tion to her fellow colleagues. Cecilia – LYNNE MAQUAT said, “In addition to his impressive young scientists who went on to and awards. the McArdle Laboratory for Cancer Arraiano, professor at the Univer- research record, Bruce has been a make signi cant impacts on the elds Stillman will receive his award dur- Research. Early in her career, she was sidade Nova de Lisboa in Portugal, leader throughout his career and has of DNA replication, cell cycle and ing the Experimental Biology 2014 Outstanding Cancer Research. making groundbreaking discoveries in said, “roughout her career, Lynne made signi cant contributions to the genomic stability. Bell echoed that conference in San Diego, where he Maquat will receive her award at the eld of RNA. has been an inspiring mentor, sup- scienti c community.” sentiment, saying: “His students and will deliver the opening lecture of the the 2014 ASBMB annual meeting Jerey Hayes, professor at the porter and motivator for other people Watson noted that Stillman’s stud- postdocs have also gone on to become ASBMB meeting. His presentation in San Diego, where she will give a University of Rochester and chairman in science, including myself.” ies of SV40 DNA and others projects leaders in their own elds.” will be at 6 p.m. Saturday, April 26, presentation. e presentation will of the biochemistry and biophysics In addition to this latest honor, led “to an understanding of DNA Stillman earned a bachelor’s degree in the San Diego Marriott Marquis take place at 2:55 p.m. Sunday, April department, said of Masquat’s post- Maquat has received much recog- replication mechanisms that dupli- from the University of Sydney and Hotel, North Tower, Hall 4. e 27, in Room 6A of the San Diego doctoral research: “Importantly, her nition, including election to the cate eukaryotic cell chromosomes.” earned a Ph.D. from the Australian ASBMB opening reception will follow Convention Center. studies established that the premature National Academy of Sciences, Stillman was able to characterize the National University. He completed a the lecture. termination of mRNA translation the American Association for the Shaila Kotadia (skotadia@asbmb. mechanism by which chromosomal postdoctoral fellowship at the CSHL Natalie Osayande (natalie. can trigger rapid mRNA degradation Advancement of Science, and the org) is an ASBMB science policy DNA replication is initiated in yeast and has since held many positions [email protected]) is an fellow. due to a process termed nonsense- American Academy of Arts and and human cells. A third major con- there, including his current posi- undergraduate at the University of mediated mRNA decay … us, even Sciences. She also is a past recipient tribution was Stillman’s clari cation of tion as president and chief executive Tampa studying biochemistry. as a postdoc, Lynne was a pioneer in of the Davey Memorial Award for how DNA replication and chromatin ocer. He has received many honors

30 ASBMB TODAY APRIL 2014 APRIL 2014 ASBMB TODAY 31 FEATURE

PHOTOS BY VICTOR LANDA, UNIVERSITY OF CALIFORNIA, RIVERSIDE

or centuries, the jewel wasp has captivated entomologists with its beauty From 1916 to 1948, Williams was an employee of the Experiment Station of and, in the case of the female, its hunting prowess. e wasp doesn’t kill the Hawaiian Sugar Planters’ Association. In May 1940, his employer sent him F its prey right away. Instead, it injects a special venom into its cockroach to New Caledonia, an archipelago in the southwest Paci c Ocean 750 miles victim, putting it into a bewitched state. e wasp then builds a burrow, drags east of Australia. Williams was to survey insects and catalog those that might in the zoned-out cockroach, lays an egg on it and buries it. e larva that devastate Hawaii’s sugarcane industry. In those days, Pan American Airways ran emerges gradually eats the cockroach alive. clippers between Hawaii and New Zealand, stopping o at New Caledonia for Over the past two decades, researchers have been trying to tease out the refueling; the concern was that the clippers inadvertently would carry insects molecular composition of this unusual venom. Not only could the results help from New Caledonia to Hawaii and harm the state’s economically valuable researchers understand how this venom acts on an animal’s central nervous crops. system, but they also could lead to a better understanding of certain human But Williams knew that New Caledonia was one of the tropical homes of neurological disorders that have some of the same symptoms as those found in the jewel wasp. He saw this survey trip as an opportunity to bring the wasp to the entranced cockroach. Hawaii and use the animal as roach control. He described the story of travel- ing with his wife to Noumea, the capital of New Caledonia, to bring back both male and female wasps to Hawaii.

e female Ampulex compressa and its taming of cockroaches were most viv- “ e jewel wasp puts up a wonderful exhibition of idly described in a 1942 paper by the entomologist Francis Xavier Williams (1). boldness, skill and strength in the attack on her often “Ampulex compressa is a large, beautiful wasp with a huge prey, once to the eect that a French scientist shining blue-green body and with the femora or thighs upon witnessing such a battle in our hotel room of the second and third pairs of legs red … Mrs. laboratory in New Caledonia, much impressed, Williams, who took great interest in this scintillating exclaimed: ‘C’est formidable!’” blue-green insect, very aptly named it the ‘jewel wasp.’” CONTINUED ON PAGE 34

32 ASBMB TODAY APRIL 2014 APRIL 2014 ASBMB TODAY 33 CONTINUED FROM PAGE 33 unusual manipulation of Periplaneta americana, the inch-long, dark brown y- ing cockroach that sends many of us screaming from the room. The proteomic analysis If you’d like In the late 1980s, Frederic Libersat was a postdoctoral fellow at Hebrew Uni- to learn more about wasp versity in Israel working on cockroaches. “I was interested in how the nervous About 15 years ago, Libersat noticed the work that Michael Adams was venom, check system generates movement,” he says. “Cockroaches are a good model to study, doing with spider venom. Libersat invited Adams, who is based at the Uni- out Ryan because their nervous system is less complicated than that of a mammal. You versity of California, Riverside, to spend some time with his group in Israel Arvidson’s can nd some rules of organization of the nervous system to produce move- to work on the jewel wasp venom. Libersat was immersed in understanding ARVIDSON poster at ment.” the neurological eects of the venom on the cockroach, but he also wanted to the ASBMB annual meeting At Hebrew University, Libersat met a visiting German scientist, Werner know the chemical composition of it. Libersat and Adams have collaborated in San Diego. Arvidson will be Rathmayer. Rathmayer was studying the bee wolf, a wasp that hunts bees, but over the years, and now both are working on the molecular composition of the presenting his poster, “Develop- he happened to have a jewel wasp in an aquarium in his oce in Germany. venom. ing the venom of the parasitoid At that time, not much was known about how the female wasp managed Both groups have taken a proteomic sequencing approach. In collaboration wasp Ampulex compressa,” to tame the cockroach. Given Libersat’s work on cockroaches, Rathmayer told with SongQin Pan, also at UC Riverside, Adams’ graduate student Ryan Arvid- between 12:15 p.m. and 1:45 him about the wasp and how it was capable of manipulating the cockroach’s son used an approach called multidimensional protein identi cation technol- p.m. on Monday, April 28, at central nervous system in mysterious ways. e wasp’s venom somehow made ogy, better known by its acronym, MudPIT. is mass-spectrometric analysis is poster board number D235. e the cockroach unable to initiate walking on its own, putting it in a state known useful for studying complex protein mixtures. abstract number is 4947. as hypokinesia. But when the wasp grabbed the cockroach by its antennae with e investigators earlier had built two databases of RNA sequences in col- its mandibles, it could lead the cockroach like a reined horse. laboration with Peter Arensburger, now at the California Polytechnic State Uni- Photo provided by Ryan Arvidson. “I thought this would give me some window into understanding how walk- versity, which they used for their MudPIT analyses to con rm that the protein ing is initiated in an insect, or any animal, as a matter of fact,” says Libersat, identi cations they made matched up with the transcripts in their databases. now at Ben Gurion University in Israel. Movement can be initiated by a To analyze wasp venom, one has to collect it. e approach is “artisanal,” stimulus, such as food, a sexual partner or scent. “But sometimes, an animal jokes Libersat, whose group developed it. A researcher rst stretches para lm also initiates what’s called exploratory movement,” says Libersat. What causes across a Petri dish with a 5-µL droplet of water. en he or she puts a female Researchers place a wasp stinger-first animals to make these movements that don’t have clear-cut rewards? wasp in a pipette tip, abdomen rst, so that the wasp’s stinger protrudes from into a pipet tip to extract its venom. And so began Libersat’s careerlong interest in the female jewel wasp and its the opening. e pipette tip then gets attached to a syringe. en, as Arvidson delicately puts it, “we antagonize the wasp.” e researcher positions the trapped wasp over the para lm-covered Petri dish and pushes the plunger of the syringe to bang the wasp on the head. e CONTINUED ON PAGE 36

A female Ampulex compressa releases 50 nL of venom in a single sting.

34 ASBMB TODAY APRIL 2014 APRIL 2014 ASBMB TODAY 35 The wasp prepares a burrow inside the jar for its bewitched victim.

CONTINUED FROM PAGE 35

infuriated wasp pierces the para lm in an attempt to sting the oender. e venom’s action has been worked out piercing action triggers venom release, and the wasp deposits about 50 nL of by using patch-clamp analyses and venom into the water droplet in the dish. e sample is then ash-frozen. A other approaches, says Libersat. e wasp can be milked up to 40 times. For their proteomic analyses, Arvidson rst venom, which contains a high says, they needed to milk about 50 wasps to get a sucient amount of sample. concentration of GABA, causes chlo- Arvidson thinks they may have found peptides that are known to aect ride channels to open up and inhibit motor function. e investigators also have found some novel peptides: ese synaptic transmission at the neurons. peptides are present in the venom at particularly high concentrations and seem to be involved in inhibiting entry of calcium into neurons through a G-protein- “It receives a sting in coupled receptor pathway. “When we put the venom on cell culture, we see the thorax, its struggles inhibition of calcium dynamics. We can talk a lot about how aecting calcium entry into a neuron can prevent it from ring, but as far as that leading to the become more feeble, and hypokinesia, we haven’t made that connection yet,” says Adams. as the Ampulex thrusts her sting deep into its throat the head is thereby Unlike some other venoms, the jewel wasp’s venom doesn’t cause paraly- forced outwards on a sis in victims. Rather, it changes the cockroach’s behavior. It’s important to remember, says Libersat, that the wasp itself doesn’t use the cockroach as a food membranous neck. After source. e wasp’s ospring needs the cockroach as food. e wasp “wants to a few moments of inject- keep (the cockroach) very much alive and fresh,” says Libersat. “e last thing it wants is muscular paralysis, which would prevent, for instance, gas exchanges ing the poison, the wasp and blood circulation. at would make the prey, which is the food item, rot releases her hold and within a few hours.” now backs o to view her Williams observed: work alertly. She may “As a rule, Ampulex attacks the cockroach soon even grasp the cockroach after the latter’s introduction into the jar. e wasp, and make pretense at then becoming very alert and with antennae directed dragging it away but usu- towards her intended victim, approaches it from ally leaves it in place — a the side in front and with a short lightning leap … wretched spectacle, head Immediately directing her exible abdomen forward down and helpless though and underneath the cockroach’s thorax, she extends not immobile and later the point of her abdomen in search of a vital place regaining considerable in which to plunge her sting … e cockroach, now activity.” thoroughly frightened, struggles furiously, twisting, e second venom goes directly straining and describing short jerky circles, parrying into the cockroach’s brain. Known with its legs, and striving particularly to tuck in its neurotransmitters, including dopa- mine, GABA and taurine, have been chin so that the tenaciously clinging wasp will not found in the venom. e dopamine sting its throat.” is thought to kick o a grooming response in the cockroach. e cock- Libersat explains that the wasp takes a two-pronged approach in taming roach stands in one spot, cleaning its its victim. e wasp rst inicts a sting to the cockroach’s thorax. e rst antennae and forelegs, while the wasp sting’s venom causes a temporary paralysis of about two to three minutes at the busies itself in getting a burrow ready. cockroach’s forelegs, which allows the wasp to get a better grip of the cock- roach’s front end and position its stinger over the cockroach’s head. e rst CONTINUED ON PAGE 38

36 ASBMB TODAY APRIL 2014 APRIL 2014 ASBMB TODAY 37 Another notable attribute of the venom, besides not causing paralysis, is that it’s reversible. If, for some reason, the wasp egg doesn’t hatch, the stung roach regains its senses ve days later inside its tomb. Laboratory studies have shown “stung cockroaches tend to live as long as control cockroaches after the sting, can lay eggs, have babies and go on about their normal lives even after the encounter with the wasp,” says Adams. Libersat adds that it’s interesting to note that ve days is exactly the time it takes for a larva to eat through a cockroach. Francis Xavier Williams Reversible eects of biomolecules are not unusual, points out Libersat. “ere are things that are secreted by your own brain that can aect you for Williams contributed more to periods of weeks or months, like a woman’s menstrual cycle,” he explains. “You the science of entomology than can imagine that there is something in the venom that has an eect that lasts just his detailed observations for a week.” and illustrations of the female Given the evolutionary conservation of the dopaminergic system between Ampulex hunting behavior. A insects and humans, the experts think that the study of the insect system may globetrotter, Williams traveled have an impact on human illnesses, such as Parkinson’s. through the Galapagos Islands, “One of the hallmarks of Parkinson disease is the inability of people to gen- the United States, the Philip- erate movement. One of the treatments of Parkinson disease is to supply them pines, parts of Central and with a precursor to dopamine because the dopaminergic system is malfunction- South America, and East Africa ing,” says Libersat. “e dopaminergic system is involved in controlling the in his pursuit of insects. initiation of locomotion in insects as well.” In his expedition to the Gala- e wasp venom’s dopamine probably attacks the cockroach’s dopaminergic pagos Islands alone, between synaptic transmission. “e cockroaches show the classical freezing movements 1905 and 1906, he collected of Parkinson-disease patients,” says Libersat. “e roaches are immobile, but more than 4,000 insects from they can generate movement in speci c conditions, such as being led by the which scores of new species were antennae by the wasp.” described. Williams himself proposed 146 new taxa in three orders of Insecta, including The hunter scrutinizes its prey. CONTINUED FROM PAGE 37 ve genera, one subgenus, 132 So much like scientists of yesterday, present-day scientists continue to be species, six subspecies and two After this 30-minute grooming stage, the cockroach falls into the zoned-out fascinated by the parasitic jewel wasp and her manipulative ways with her replacement names (2). state of hypokinesia. cockroach victim. As Williams described, it wasn’t just scientists who found this In his career of six decades, Once the wasp has prepared a burrow and pulled the cockroach in, it glues wasp to be a wonder to behold: Williams published 286 an egg to the underside of the bug and buries it. e egg hatches, and the scienti c papers as well as larva grows latched on the cockroach. Once the larva has grown its nal set of “On our Pan American Airways voyage from the 400-page reference book mandibles, it begins to chew into the roach, eventually climbing in completely. Nouméa to Honolulu, we stopped for a day and a “Handbook of the Insects and Inside the still-living host, the larva enters the pupal stage, forms a cocoon and Other Invertebrates of Hawai- matures. It emerges as a fully formed wasp. half at the equatorial atoll of Canton. Here the two ian Sugar Cane Fields.” In 1946, Ampulex jars were brought out of their travel bags, a Williams published a popular “ e last pair of jaws are large and stout-toothed, book, “Mike the Minah,” which large cockroach was given to each of the wasps, and and it is with these that the larva immediately bites he had coauthored with his wife the airplane passengers, the airplane and the ground Louisa Clark Williams. He died through the cockroach’s body to enter it and feed in California, the state where he crews were treated to an exciting rough-and-tumble within … e larva now feeds ravenously within its was born, in 1967 at age 85. performance.” weakening host, hollowing out its body even to the Rajendrani Mukhopadhyay (rmuk- base of the legs. e cockroach soon perishes — [email protected]) is the having provided the wasp during its life as a grub REFERENCES senior science writer and blogger 1. Williams, F. X. Proc. Haw. Ent. Soc., XI, 2 (1942). for ASBMB. Follow her on Twitter at www.twitter.com/rajmukhop. with a continuous supply of fresh meat.” 2. Arnaud, P.H. Jr. Occasional Papers California Acad. Sciences, 80 (1970).

38 ASBMB TODAY APRIL 2014 APRIL 2014 ASBMB TODAY 39 lated. I became more excited. Now it is estimated that least 10 percent of When life is dicult, I look at the DNA sequence mammalian genes contain overlap- ping sequences. To me, the fact that on my desk. From its intricate beauty, I draw strength interlocking DNA sequences produce and hope for the future. unique, functional proteins across the biological spectrum is remarkable. I a ribosomal RNA. Ribosomal RNA have our overlapping-genes moments. feel that I am looking at something serves as a structural backbone for Something in our eld of study stirs that transcends mere biology. protein-synthesizing ribosomes. is our soul and evokes wonder. It may As I reect on these overlapping is a completely dierent RNA func- not be a DNA sequence. It could be genes, I am thankful for several tion than that of messenger RNA. a protein with amazing properties, an reasons – some obvious, others Scientists who study overlapping intricate signal=transduction net- perhaps not so obvious. At the genes use words like “novel,” “remark- work, a cell with marvelous abilities functional level, many of these genes are essential for disease prevention, able,” “striking” and “statistically or a novel organism that provides longevity and life itself. I display on improbable” to describe them. new insights. But whatever it is, for my desk the sequence for the INK4a/ At the spiritual level, overlap- a moment it captivates us. And if Thank God ARF gene because, as a gerontol- ping genes give me a glimpse of a we take time to reect on it, maybe ogy researcher, this locus is very reality that transcends our everyday it will lighten our daily burden of important to me. ese proteins play world. Writers as dierent as Richard grants, papers and paperwork. for overlapping genes a major role in tumor suppression Dawkins (“An Appetite for Wonder”), Looking at the big picture, we and perhaps the aging process itself. Stephen Jay Gould (“Wonderful scientists can be thankful that we By Harvey J. Armbrecht ese two proteins are regulated by Life”), Ursula Goodenough (“e get to study biochemical systems as separate promoters, and they function Sacred Depths of Nature”), Stuart wonderful as overlapping genes. We in independent tumor-suppressor Kauman (“Reinventing the Sacred”) get to apply our knowledge of them and the author of Psalm 139 (“I am to the treatment of human diseases. ometimes I feel weighed down single stretch of DNA sequence codes is results in an alternate reading pathways. Mutations in this locus as a scientist. Sometimes I for parts of two proteins. In the case frame – hence the name ARF protein. result in a marked increase in tumors fearfully and wonderfully made”) We get to talk and write about them S feel overwhelmed by grant of INK4a/ARF, the in-frame read- Amazingly, the overlapped coding in mouse models, and these genes make the point that what we study is and perhaps inspire others. We get to deadlines, unwritten papers, nicky ing of the DNA codes for the amino of these two proteins continues for are frequently inactivated in human wonderful, transcendent, even sacred. enjoy their beauty and the meaning experiments, endless forms, and so acids of the INK4a protein (shown 105 amino acids. e same DNA tumors. To me, overlapping genes point to that they bring to our own lives. And forth. Why am I doing this? Isn’t in blue above) in a perfectly conven- sequence produces long stretches of At the personal level, I am thank- something greater than myself. When maybe we even put a picture of them there an easier way to earn a living? tional way. But in the middle of this, two completely dierent proteins ful for overlapping genes because they life is dicult, I look at the DNA on our desk. During times like this, I’ll sometimes the DNA also codes for dierent with dierent three-dimensional remind me of the beauty of the things sequence on my desk. From its intri- glance over to the corner of my desk. amino acids for a completely dierent structures and functions! we biochemists study. ese genes cate beauty, I draw strength and hope for the future. Harvey J. (Jim) Armbrecht (arm- ere I display pictures of special I rst heard come in a wide variety of motifs. [email protected]) earned a B.S. people and things – my wife, my about overlap- Sometimes the overlap is on the same Since this is a letter of thanks, who in physics from Drexel University children, my grandchildren … and ping genes years coding strand, as it is for the INK4a/ then do we thank? Who do we thank and a Ph.D. in biophysics from the University of Rochester Medical a DNA sequence. Now, pictures of ago in the virus ARF gene locus. But sometimes the for the function, beauty and spiri- tuality of these overlapping genes? School. He is a research biochemist at the St. family are understandable, but why a PhiX174. e code for the second protein is on the Louis VA Medical Center and professor emeritus in DNA sequence? amount of DNA complementary (antisense) strand. It Depending on one’s worldview, a the Division of Geriatric Medicine and the Depart- e DNA sequence I have on my in the genome of can even be on the complementary person might thank God, nature, evo- ment of Biochemistry and Molecular Biology at St. Louis University School of Medicine. His major desk is from the INK4a/ARF gene this virus is too strand read backward! lution or perhaps all of these. Being a person of faith, I would thank God research interests have been age-related changes locus. e DNA sequence (shown in small to produce Probably my favorite overlapping in calcium and vitamin-D metabolism. More black) and the corresponding proteins the 11 proteins it sequence involves the yeast protein rst. But whatever one’s answer, it is recently he has been studying age-related memory it codes for (shown in blue and red) needs. To over- Tar1p. Here the messenger RNA a question that these genes confront loss in animal models. His current interests are in the biochemistry of aging and dementia and read in part: come this, the sequence that codes for Tar1p also us with. codes, on the antisense strand, for I think that all of us as scientists caregiving. INK4a DNA: …ATT CAG GTG ATG ATG ATG GGC AAC GTT CAC GTA GCA GCT… genome contains INK4a protein: …Ile-Gln-Val-Met-Met-Met-Gly-Asn-Val-His-Val-Ala-Ala… multiple overlapping genes. I was ARF protein: …Asp-Asp-Asp-Gly-Gln-Arg-Ser-Arg-Ser-Ser… intrigued by this clever strategy, but it was only a virus. en it gradually Enjoying the Open Letters series? is DNA sequence is an exqui- protein – the ARF protein (shown became clear that it was not just a site example of an overlapping gene. in red above). It does this by shifting virus thing. Examples of overlapping We’ve extended the submission deadline to Oct. 1. Send yours to [email protected]. Overlapping genes are genes where a the reading frame of the triplet code. genes in mammals gradually accumu-

40 ASBMB TODAY APRIL 2014 APRIL 2014 ASBMB TODAY 41 OPEN CHANNELS Petsko on the Ph.D. pipeline Former ASBMB president weighs in on mentoring, postdoctoral training and alternative careers in science By Lymor Ringer-Barnhard

regory academic research. When asked about the academic track, Petsko recom- Petsko, what needs to be done to familiarize mends that you “stay until you stop G a struc- Ph.D. students with careers outside of learning.” He also stressed that the tural biologist research, Petsko said that he believes point of a postdoctoral period was at Brandeis that responsibility lies mainly with to provide advanced training – in University graduate schools, likely in the form research. and a former of postdoctoral or career-training For postdoctoral fellows to obtain president of oces. He also said graduate schools jobs outside of academia, Petsko the American should provide internship opportuni- indicated that the responsibility lies Society for Biochemistry and ties in nonacademic elds, such as in largely with the institution to provide Molecular Biology, sat down recently industry. proper career guidance. He also for a Google Hangout to answer One audience member asked why mentioned the importance of pro- questions from students and post- many mentors are hesitant to support fessional societies to host job fairs doctoral fellows regarding the Ph.D. students pursuing careers outside of showcasing a variety of career types. pipeline, postdoctoral training, research. Petsko said this is not simply If this is not happening, it is up to careers in science and funding issues. the single-mindedness of the mentor the young scientists to petition for it, In his interview, which is archived but rather “plain stupidity.” he said. online (1), he emphasizes the need He continued: “e idea that “Every scienti c society that I am to make major changes to Ph.D. and there can be no plan B is simply a aware of is scared to death about the postdoctoral training programs in the failure on the part of the mentor to fact that their membership tends to U.S. be a proper mentor. e job of the look like me: white, middle-aged e conversation with Petsko mentor is not to provide clones of males. If the young members of a was hosted by iBiology, an initiative him or herself. e job of the mentor society got together and made enough started in 2006 to make scienti c is to help the person become the best noise, societies would be responsive presentations available to the public. that they can be.” To further stress to what they want, because societies Petsko’s talk is one of more than 300 his point, Petsko added that “If they desperately need their young mem- produced by iBiology. don’t see that as the job, then they’ve bers right now.” Many audience members asked got no business mentoring.” Meanwhile, Petsko said that fewer Petsko about careers beyond academic Petsko said he does not think postdoctoral positions should exist in research. Petsko was cautious when that Ph.D.s should do postdoctoral order to pay postdocs higher salaries. describing those careers as “alterna- fellowships unless they plan to stay e goal is to not “make postdocs the tive” because, in fact, most Ph.D. in academia, but if you are a postdoc default,” he says but rather to make it graduates do something other than who does not want to continue along a desirable position that is competi- tive and that people pursue to stay in academia. “We need to have much “ e idea that there can be no plan B is simply a (closer to) the correct number of failure on the part of the mentor to be a proper mentor. graduate students becoming postdocs relative to the number of postdocs e job of the mentor is not to provide clones of him that nd advanced positions,” says or herself. e job of the mentor is to help the person Petsko. become the best that they can be.” When asked about the most eec- CONTINUED ON PAGE 44

APRIL 2014 ASBMB TODAY 43 CONTINUED FROM PAGE 43 paper review, proposal writing, teach- to do good science at an academic ing and so forth to further challenge institution is being a faculty mem- tive way for a postdoc to get the best themselves, he said. ber.” Petsko admitted funding those mentoring, Petsko replied, “I think Petsko also said that he is a rm types of positions would be the main the best mentees are those that make believer that labs in the U.S. should hurdle for creating them, but he said sure I don’t forget them; they don’t that he believes it would be possible. fall between the cracks.” He also take some pointers from European To see the complete video of mentioned that what you get out of a labs and create more nontenure track, Petsko’s interview and a full break- postdoc is “highly individualistic” and permanent research positions. In down of each question and answer, go that it is a research training position, Europe, people who obtain positions so postdocs need to make sure they like that are “exceptionally well- to http://bit.ly/1HPOH. continue learning. To be successful, trained to do high very high-powered postdocs should be proactive and ask research,” he said, adding that “it’s Lymor Ringer-Barnhard (lymor. their mentors to let them help with stupid to assume that the only way [email protected]) earned a Ph.D. in tumor biology from Georgetown University. She is REFERENCE a postdoctoral fellow at Johns Hopkins University. 1. http://bit.ly/1HPOH

The University of Vermont has openings for both Ph.D. and postdoctoral training positions in fields related to blood coagulation research, encompassing vascular biology, hemostasis, hemorrhagic diseases and thrombosis. Programs extend over a broad range of basic, translational and population science. Graduate students and M.D. and Ph.D. fellows are invited to apply for positions in this NIH-sponsored training program leading to either the Ph.D. degree or to postdoctoral studies. Past fellows have been from the fields of Biochemistry, Cell Biology, Hematology, Cardiology, Surgery, and Pathology. For fellows pursuing hematology-oncology training, integration with clinical training is offered. Specific areas of interest include: • Blood coagulation reaction mechanisms • Biochemical/biophysical/X-ray structural characterizations of protein-protein, protein-metal ion, and protein-membrane interactions • Dynamics and proteomics of the blood coagulation/fibrinolytic systems • Platelet/megakaryocyte biology • Epidemiology • Treatment of hemophilia and venous thrombosis, and thrombosis prevention Participating mentors are in the fields of Biochemistry, Pathology, Cardiology, Hematology, Epidemiology, Surgery, Genetics, Vascular Biology and Cell Biology. Applicants must be citizens, noncitizen nationals or permanent residents of the U.S. Additional information can be found on our websites: http://biochem.uvm.edu/ www.med.uvm.edu/lcbr www.med.uvm.edu/pathology www.fletcherallen.org/services/heart_health/specialties/cardiology www.uvm.edu www.fletcheraller.org

Minorities and women are encouraged to apply. Send inquiries to: Dr. Kenneth G. Mann, University of Vermont College of Medicine, Department of Biochemistry, 208 South Park Dr. Rm 235, Colchester, VT 05446 or email [email protected].

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