Vol. 13 / No. 8 / September 2014

THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY CONTENTS

NEWS FEATURES PERSPECTIVES

2 28 38 ON THE COVER PUNKS WHO PUBLISH OPEN LETTERS 2015 CALLS FOR 29 Introduction Open letter to the incoming cohort 3 30 Milo Aukerman of Descendents of graduate students EDITOR’S NOTE 32 Dexter Holland of e Ospring 34 Greg Gran of Bad Religion 40 SUBMISSIONS EDUCATION 4 22 A response to the NIH Biomedical Research PRESIDENT’S MESSAGE Workforce Working Group Report HOBBIES e curse of committees and clubs We know that a life in science can be grueling. We also know that some of you 43 have very interesting or unusual ways of blowing o steam or nding your Zen. 6 PROFESSIONAL DEVLOPMENT We would like to feature your essays, poems, artwork or multimedia reecting on MEMBER UPDATE Passive obstructionism scientists’ pastimes. We welcome all creative interpretations of the theme. You could send us a photo of you shooting hoops or jumping out of an airplane. You could 44 send us a video of you jamming with your band. You could send us a poem about a 8 NIH UPDATE OUTREACH childhood hobby or otherwise abandoned escapes. You could write about a hobby enjoyed by someone else — perhaps a gure in science history or one of your men- 44 Scientists talking genetics with the public tors. And you could send us a rant about how you don’t have time for such frivolity. 9 46 ASBMB grants help UAN chapters NEWS FROM THE HILL do outreach Regular maintenance required 12 44 GENERATIONS is collection of essays, poems and artwork will explore generations in a very 10 loosely dened way. You might have come from a family of scientists. You might NEWS have insights about parenting while doing science. You might have something to say New JBC/Herb Tabor about generations of cell lines or scientic lines of inquiry. You might have a story Young Investigator Award winners to tell about a line of researchers mentored by one scientist. Interpret the theme as you will. It is not a boundary but rather a springboard for the making of meaning. 12 RETROSPECTIVE Roy P. Mackal, 1935 – 2013 DEADLINES FOR HOBBIES AND GENERATIONS: Dec. 31, 2014. FORMAT: We’ll print some; others, we will post online. Some might appear both in print 13 and online. IN MEMORIAM SUBMISSIONS: Email (to [email protected]) your manuscripts as Word documents, static images as JPEG or TIFF les (the higher the resolution the better), audio as mp3 or 16 28 38 mp4 les, and videos in something like QuickTime, Vimeo or YouTube. Please indicate to JOURNAL NEWS In the rst part which series you are submitting in your email subject line. of our “Defying Stereotypes” 20 series, Rajendrani Mukhopadhyay and LIPID NEWS Geo Hunt write about three punk rockers who also do 22 science. For image 2015 ANNUAL MEETING credits see page 36.

SEPTEMBER 2014 ASBMB TODAY 1 ON THE COVER EDITOR’S NOTE

THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY Defying stereotypes Death notices

OFFICERS COUNCIL MEMBERS Steven McKnight Natalie Ahn magine you are at a social event, paths away from the lab bench. e ne important but sobering duty spective article. It’s especially helpful he abandoned the bench to track President Squire J. Booker such as a wedding reception or number of workers with STEM I have as editor of this maga- when colleagues o er to write it. down elusive beasts. He apparently

Jeremy M. Berg Karen G. Fleming I a birthday party. Between toasts Ph.D.s employed in academia has O zine is to report the deaths of Another consideration is how long remained an ASBMB member until Past President Gregory Gatto Jr. and appetizers, somebody asks you decreased by nearly 20 percent since our members. We have thousands of ago the member passed away. In most his death last year. Karen Allen Daniel Leahy what you do. For most people, it’s members, of course, and I certainly cases, if more than a few months have I found lots of reporting on Secretary 1973 (1), with almost 30 percent now Anjana Rao not a big deal to answer the ques- employed in nonresearch positions don’t know them all personally, but I passed, a news magazine like ours Mackal’s adventures, including a Toni Antalis Jared Rutter Treasurer tion. But for you, as scientists, it’s a appreciate that a stranger to me is a has, by industry standards, missed its People magazine interview with Brenda Schulman (2). Setting aside the implications for very special person to another. window. But there are exceptions, like him before he set o for the Congo Michael Summers dreaded question, because as soon as the future of the scientic enterprise, EX-OFFICIO MEMBERS you announce your profession, you these trends show that the traditional, In most cases, word of a recent one in this month’s issue. swamps to nd what might have been Dorothy Beckett ASBMB TODAY EDITORIAL pretty much know what the reaction stereotypical view of scientists is death trickles in. In early July, Cindy sent what I “the last of the dinosaurs.” I watched Mary Roberts Co-chairs, 2015 Annual ADVISORY BOARD will be. crumbling. Our executive director, Barbara thought at rst was a typical death videos of him and about creatures I’d Meeting Program Charles Brenner Scientists are assumed to be e series also will explore how Gordon, who seems to know just notice, but I couldn’t have been more never heard of. I cruised cryptozool- Committee Chair about everybody, often spots death wrong. She provided a link to an ogy websites – some serious and some Michael Bradley socially inept and far too smart for the characteristics and qualities that Peter J. Kennelly announcements and lets me know. obituary, like she usually does. She not so much. (Cryptozoology, by the Chair, Education and Floyd “Ski” Chilton mere mortals. While people in other make scientists who they are also Professional Development Cristy Gelling professions are understood to come in make musicians, athletes, artists and Cindy Whalen, our membership also provided a link to a Wikipedia way, is the study of hidden animals Committee Peter J. Kennelly all shapes and sizes, those of us with others who they are. Our hope is that coordinator, periodically checks our page, which was a little odd. And she and often derided as a eld.) Daniel Raben list of emeritus members so that she included a note: “I love this one.” I Mackal passed away on Sept. 13, Chair, Meetings Committee Rajini Rao lives in science are dened by cari- nonscientist readers will appreciate Yolanda Sanchez can keep our records updated. And was intrigued. 2013. I’ve written an obituary for this Takita Felder Sumter cature: Only certain kinds of people that being a scientist doesn’t mean Chair, Minority Aairs Shiladitya Sengupta are scientists, and scientists are only anything other than enjoying science sometimes members will notify us I clicked the rst link. e headline longtime member who was not at all Committee Carol Shoulders certain kinds of people. and that scientist readers will appreci- when their colleagues have passed read, “Loch Ness Monster & Mokele- representative of our general mem- omas Baldwin In a series of articles launching in away. Mbembe Researcher, Cryptozoologist bership but who was nonetheless a Chair, Outreach Committee ate that they have what it takes to do ASBMB TODAY this issue of ASBMB Today, we aim anything they want. Hence the name You might wonder how we deter- Roy P. Mackal Has Died.” It wasn’t larger-than-life character. You can nd Bob Matthews Angela Hopp mine which obituaries to include making sense. is fellow was an the article on page 12. I apologize for Chair, Public Aairs Editor, [email protected] to alter, if not completely vanquish, of this series: “Defying stereotypes.” Advisory Committee in the magazine. If the member has ASBMB member? its lateness, but I hope you enjoy it. Rajendrani Mukhopadhyay this stereotypical image of a scientist. Kathleen Collins Sr. Science Writer, e series presents proles of indi- made key discoveries or held leader- As a matter of fact, Mackal joined Chair, Publications [email protected] ship positions with the society or its the society in 1953, back when he was Sincerely, Committee viduals who have scientic know-how Marnay Harris journals, we do our best to recognize a young biochemistry faculty member Angela Hopp Martha J. Fedor Designer, [email protected] but who have made their names in Editor-in-chief, JBC his or her contributions in a Retro- at the University of Chicago, before Editor, ASBMB Today Ciarán Finn completely di erent elds. Some Herbert Tabor Web Assistant, c[email protected] of those featured might be obvious; Co-editor, JBC Karen Schools Colson others might surprise you. In some A. L. Burlingame Director of Publications, Editor, MCP [email protected] cases, science clearly has inspired their Edward A. Dennis Barbara Gordon current work; in others, science has UNDERGRADUATE RESEARCH IN THE MOLECULAR SCIENCES 2014 Joseph L. Witztum Executive Director, served as only a stepping stone along Co-editors, JLR [email protected] their career paths. Regardless of how at Minnesota State University Moorhead those featured in this series got to where they are now, their stories Minnesota State University Moorhead invites Keynote speaker: For information on advertising, contact Fox Associates Inc. undergraduate researchers and mentors from the Catherine Smith, MMSc. at 800-440-0231 or [email protected]. demonstrate that having a science background doesn’t limit the possi- surrounding area to participate in a regional meeting Inuenza Division, bilities of what someone can of the ASBMB Undergraduate Aliate Network. Centers for Disease is meeting will feature oral and poster presenta- Control and Prevention, accomplish. Read our rst installment of the tions by undergraduate researchers, workshops, networking opportuni- Atlanta, Ga. www.asbmb.org/asbmbtoday e series comes at a time when series on page 28. PRINT ISSN 2372-0409 scientists increasingly are taking ties, and talks by industry and academic professionals. e oral and Applying Next-Generation Sequence Articles published in ASBMB Today reect solely the poster presentations will be judged, and four winners will receive travel Technology to the Understanding of authors’ views and not the ocial positions of the awards for the ASBMB annual meeting in Boston in March. Inuenza Virus Populations American Society for Biochemistry and Molecular REFERENCES Biology or the institutions with which the authors are 1. http://www.nsf.gov/statistics/seind14/content/etc/nsb1401.pdf aliated. Endorsement by ASBMB Today or ASBMB of products or services mentioned is not implied. 2. http://acd.od.nih.gov/biomedical_research_wgreport.pdf The deadline for abstract submission is Sept. 27. For more information, visit www.mnstate.edu/urms.

2 ASBMB TODAY SEPTEMBER 2014 SEPTEMBER 2014 ASBMB TODAY 3 PRESIDENT’S MESSAGE

grant-review process. Likewise, achievement. ese committees are, unfortunately, study sections are unfortunately, equally good at spot- Committee Commitment The curse of committees undoubtedly contaminated by ting and excluding the most creative Committed ri -ra . proposals — the grant applications A second cause of the demise in coming from inspired scientists By Ron Laskey study section quality can be attrib- whose research is damned because As I enter the lab every morning and clubs uted to the fact that it is a thankless it is several steps ahead of the curve Each time a sad sight makes me stop task balanced by few benets. ree and damned because it comes from An entire European paper mountain By Steven McKnight Has piled up upon my desk top. to four decades ago, it was a feather an applicant not blessed with club ey want me to join their Committees in one’s cap to be appointed to an membership. And to referee papers as well NIH study section. When I joined Now, to the second of two evils: To comment on grants and promotions Endless paper that makes my bin swell. start this essay by directing you it to be awed. What went wrong? science for the right reason — inquiry the molecular cytology study section the evolution of scientic clubs. to the lyrics of a song written I submit that the demise of the into the unknown. in the 1980s, Bruce Alberts was chair- Back when we used to “walk miles (Chorus) I by Ron Laskey, co-discoverer review process can be attributed to Once the budget of the NIH man, and the committee included to school,” the scientic meetings we Committee, Commitment, Committed the likes of Tom Pollard and all kinds attended had some level of breadth. ree words that are tricky to spell. of nuclear localization signals (see two changes. First, the quality of began to grow modestly in the 1970s, Committee, Commitment, Committed box). In the song, Ron laments about scientists participating in CSR study it was easy to nd highly qualied of superb scientists. To spend three Among all meetings I attended back ree problems that make my life hell. the beating of committees, a neces- sections two to three decades ago was, scientists to sta the study sections. meetings per year with an esteemed in the 1970s and 1980s, the two sary evil of governance in most all on average, superior to the quality ese were practicing scientists group of scientists was both inspira- best were the Gordon Conference on But I think that I’ve just found an answer To stop all this nonsense I’ll try domains of society. Some people of study section participants today. who knew how to perform experi- tional to me as a young scientist and Biological Regulatory Mechanisms And next time they ask my opinion gravitate to committees, yet this is Second, study sections have become ments with their own hands. Given of tangible value to my maturation as and the Arolla Workshop. Both were Well here’s what I’m going to reply: not the natural attraction for most highly specialized such that they nar- that they were also educators, most a researcher. relatively small meetings, including So you want me to join your committee ere are many reasons things have only perhaps 100 to 150 partici- But its members are worse than dead sheep of us who love adventure into the rowly dene a di erentiated club of such scientists were endowed with a ere’s only one reason I’d join unknown of scientic exploration. biomedical research. breadth of knowledge in biology or changed. Government restrictions pants. Despite the small size of these It’s the chance to catch up with my sleep. e majority of United States Let me rst o er ideas as to why medicine or both. mean that study section participants meetings, both sported an intellec- And you want my review on that rubbish scientists involved in biomedical and how the quality of our scientic Between then and now, the size of can hardly get a cup of free co ee. tually thrilling breadth of scientic What they claim in that junk I can’t tell I suggest you accept it without any change research must win external grant review panels has diminished. ere- the enterprise has grown by a whop- e pay, especially when factoring in scope. One might hear about mobile It will t in your Journal so well. funding in order to practice our after, I will speak to clubs, including ping degree. e budget of the NIH the time required to properly review genetic elements in maize, mating craft. e National Institutes of thoughts on how they evolved and was roughly $1 billion in 1970. Last dozens of applications, is pathetic. type switching in yeast (where sirtuin (Chorus) Health is, by far, our most substan- how they insidiously poisoned our year, it was $29 billion — a growth of Career benet from study section proteins came from), UV-mediated So you need a new Head of Department tive paymaster. We compose our research enterprise. 2,900 percent. It is self-evident that it participation for top-tier scientists, release of phage lambda from its And you want me to recommend one grant applications and then submit Among all problems leading to takes a whale of a lot more reviewers young or old, is marginal. Finally, lysogeic state, or the genetics of pat- I suggest that you try resurrecting as study sections have become ever tern formation in fruit y embryos. at nice man Attilla the Hun them for evaluation via the Center for devolution of CSR study sections, and study sections to distribute $29 He’d soon put a stop to your ddles Scientic Review. After receipt of an the elephantine expansion of the billion per year than $1 billion. more dedicated to thin slices of the Methods of genetics, biochemistry And bring all you mavericks to heel application, the CSR assigns it to a biomedical research complex tops the Yes, the CSR is able to corral the biomedical landscape, participants and molecular biology were applied And you asked about hiring that postdoc review committee commonly called a list. Biomedical research in the 1960s personnel required to deal with this are exposed to less and less science to zoo- or botanical garden-like dis- So I’ll tell you the things that I feel. at fool needs a transplanted brain study section. e CSR organizes and and 1970s was a spartan game. Pro- huge increase in grant evaluation. I outside of the narrowly dened tributions of animals, microbes and He spends all his time in the bar manages hundreds of study sections totypically, scientists were employed submit, however, that the quality of disciplines covered by their individual plants. When one left such meetings, I suggest that you hire him without a delay such that every slice of the pie of as teaching faculty members at study section membership has eroded study sections. As such, one rarely horizons of perspective were broad- In your lab he’d shine like a star. our biomedical research enterprise is universities. Carving out what time signicantly. Here are several reasons learns much of anything new by ened. Boy, were those meetings fun. (Chorus) covered. they could manage relative to their to explain the erosion. participating in an NIH study section Fast-forward 30 years, and what Individual grant applications are primary roles as educators, scientists First, the average scientist today is meeting. do we now have? e typical modern And now that I’ve sent o these letters typically assigned to three review- worked in a focused manner on dis- not of the quality of our predecessors; Before turning from committees biomedical meeting spends a week ey won’t trouble me any more So I’ll take up hang-gliding and skydiving too ers within a study section composed crete problems in biology or medi- it’s a bit analogous to the so-called to clubs, let’s consider what might be on a ridiculously thin slice of biology. I’ll play with my children and show them the zoo of 20 to 30 scientists. Reviewers cine. ey worked with perhaps a “greatest generation” of men and expected from a grant review com- ere are entire meetings devoted to I’ll even have time for experiments too read and evaluate their assigned single technician or graduate student women of the United States who mittee composed largely of second- the hypoxic response pathway, sirtuin It’s a new life I’m starting today All commitments I’m throwing away. grant applications before the entire and needed modest support from fought o fascism in World War II tier scientists with limited knowledge proteins, P53, mTor or NFkB. If a committee meets. e study section external funding sources. e glory of compared with their baby boomer of the breadth of biology and medi- scientist studies some aspect of any of From CD “Selected Songs for Cynical then, as a committee, systematically the experience was straightforward: children. Biomedical research is a cine. I propose that these committees these domains, he or she absolutely Scientists” ranks all applications as a means of Could a scientist make a discovery? It huge enterprise now; it attracts ri - are equally good at ensuring that the has to attend these mindless meet- © 2003 Cold Spring Harbor Laboratory Press prioritizing those most suitable for was that simple. It was not a high- ra who never would have survived worst and best applications never get ings where, at most, some miniscule funding. ying game but instead a relatively as scientists in the 1960s and 1970s. funded. ey can see a terrible grant increment of advancement is all to be Two or three decades ago, this modest enterprise composed primar- ere is no doubt that highly capable wherein the science is awed and the learned. system was e ective, yet I now judge ily of men and women who practiced scientists currently participate in the investigator has no track record of CONTINUED ON PAGE 7

4 ASBMB TODAY SEPTEMBER 2014 SEPTEMBER 2014 ASBMB TODAY 5 MEMBER UPDATE

He continued: “For example, it Gierasch of the University of symptoms can range from mild to might be appropriate to focus some Massachusetts Amherst. very severe, most a ected individuals Crane, Jez and Johnson named HHMI professors attention on emerging pedagogies in e Council of Councils has 27 have similar physical characteristics: distance education, continuing rene- members, all of whom are nominated stunted growth; small hands and ments in professional and medical by the NIH institutes, centers and an feet; thin eyebrows that meet in the education, strategies for overcoming advisory committee to the director. middle; long eyelashes; upturned the challenges faced by underserved e councilors are called upon to pro- noses; and thin, downturned lips. students, and the emergence of vide insights with regard to scientic Common medical problems include under-recognized educational com- policy and make research recommen- gastroesophageal reux, bowel mal- mittees.” dations about lines of research that rotation, hearing loss and congenital Ortiz is a past member of the are emerging or deserving of special heart defects. ASBMB Minority A airs Committee. emphasis. Gerton and her team recently linked a dampened growth signal to Roberts syndrome, a related condi- Belfort, Cuervo and Nonprofit invests in tion that responded well to treatment CRANE JEZ JOHNSON Gierasch named to Gerton’s work on Cornelia with L-leucine in RBS zebrash. NIH Council of Councils de Lange syndrome “Both RBS and CdLS are caused e Howard Hughes Medical Institute has awarded $1 million each to three members of the American by mutations that a ect cohesin, e Cornelia de although the molecular basis of CdLS Society for Biochemistry and Molecular Biology. Lange Syndrome Brian Crane of Cornell University, Joseph Jez of Washington University and Tracy Johnson of the is less well understood,” she says. “A Foundation logical next step was to determine University of California, Los Angeles, were among the 15 people named as the 2014 HHMI professors. selected Stow- whether our work on RBS has any e awards, which will be dispersed over ve years, are intended to support the integration of research ers Institute for relationship to CdLS.” with undergraduate teaching. Medical Research BELFORT CUERVO GERTON Founded in 1981, the Cornelia In a statement, HHMI said: “HHMI professors are accomplished research scientists who are making investigator Jen- de Lange Syndrome Foundation is a science more engaging for undergraduates. By providing HHMI professors with the funds and support ree ASBMB nifer Gerton as the recipient of a national family support organization to implement their ideas, HHMI hopes to empower these individuals to create new models for teach- members were research grant. Gerton will use the that exists to ensure early and accu- ing science at research universities.” named earlier funding to study Cornelia de Lange rate diagnosis of CdLS, to promote e honors resulted from a competition for professors at the 106 research universities deemed by this year to the syndrome in a zebrash model of the research into the causes and manifes- the Carnegie Foundation for the Advancement of Teaching as having very high research activity. In National Insti- disease and to determine whether tations of the syndrome, and to help tutes of Health’s some developmental defects can be the end, there were 173 proposals judged by a panel of scientists and educators. Finalists were called to GIERASCH people with a CdLS diagnosis and Council of ameliorated through treatment with their families to make informed deci- make presentations at HHMI in May. (IMAGES COURTESY OF PAUL MORIGI OF HHMI) Councils, an advisory body that the amino acid L-leucine. sions throughout their lifetimes. counsels the NIH director. ey Cornelia de Lange syndrome is a A version of this article appeared in were Marlene Belfort of University developmental disorder that a ects the Stowers Report, published by the a Howard Hughes Medical Institute Bassler and Dikic win Ortiz named editor-in-chief at Albany, Ana M. Cuervo of Albert males and females equally across all Stowers Institute for Medical Research. It investigator. Dikic is the director of Einstein College of Medicine and Lila human populations. Although the has been adapted here with permission. Vallee Foundation the Institute for Biochemistry and of journal BAMBEd visiting professorships scientic director of the Buchman Phillip Ortiz, the Institute at Goethe. ey were among assistant provost six honorees chosen this year for the for undergraduate program. education at the PRESIDENT’S MESSAGE CONTINUED All of the winners will be sup- State University of New York, has CONTINUED FROM PAGE 5 score from a study section wherein similar warning: Beware of the bio- ported by the foundation as they ORTIZ embark upon various pursuits of been named edi- Damn the fool who does not the applicant is not a club member is medical industrial complex. In subse- BASSLER DIKIC intellectual exchange at institutes tor-in-chief of the journal Biochemis- attend these meetings: e conse- to be equated with idiocy. quent essays, I will o er ideas on how Bonnie Bassler of Princeton Univer- worldwide. Dozens of research- try and Molecular Biology Education, quence is failure to maintain club Whether clubs came from commit- we might reverse untoward trends. sity and Ivan Dikic of Goethe Univer- ers, about a third of them ASBMB commonly known as BAMBEd. membership. And why is club mem- tees or vice versa matters not – that sity have won Vallee Foundation members, have won Vallee professor- In a letter to readers, Ortiz said bership of such vital importance? Yes, is where evolution of our biomedical Steven McKnight (steven. he, along with the editorial board, enterprise has taken us. Upon closing [email protected]) visiting professorships, which allow ships over the years. e program will precisely, there is nearly a one-to-one is president of the American senior scientists to spend four weeks begin accepting nominations again in will “determine areas that the journal correspondence between these clubs out his presidency in 1960, Dwight Society for Biochemistry and in other labs around the world. October. Recipients are allowed up might explore so that it can con- and CSR study sections. To think Eisenhower o ered the cautionary Molecular Biology and chairman Bassler is the chair of Princeton’s to two years to take advantage of the tinue to meet the needs of educators that a grant applicant would have statement, “Beware of the military of the biochemistry department at the University of Texas-Southwestern Medical Center at Dallas. molecular biology department and visiting professorships. throughout the world.” even a prayer of winning a fundable industrial complex.” I close with a

6 ASBMB TODAY SEPTEMBER 2014 SEPTEMBER 2014 ASBMB TODAY 7 NIH UPDATE NEWS FROM THE HILL Researchers reveal important Regular maintenance required gene in early cilia development By Benjamin Corb By Elizabeth Meier ast month, it was time to get new tires for my car. A simple How Legislators Perceive Issues L tire change turned into a tire POLICY change and a brake job, rotors and Connected to legislator’s Not connected to legislator’s he primary cilium is a micro- goals/consistent with values goals/consistent with values pads. Five hours later, and with my tubule-based organelle with • • wallet nearly $2,000 lighter, I was Issues/projects that impact local Issues/projects important to key T important sensory and signaling economy political supporters back on the road. Sadly, very few functions. ese specialized exten- • Issues/projects that impact or interest • Issues/projects important to elected people took the time to compli- many constituents officials sions transduce mechanical and Important to ment me on how fantastic my tires constituent s chemical stimuli to support cellular • Issues/projects that have significant • Issues/projects with significant impact on state or nation coalition support functions, such as organogenesis and looked or how fresh and smooth my braking was. My costly — yet tissue homeostasis, and the absence or • Issues/projects with personal • Issues/projects important to POLITICS malfunction of primary cilia underlies necessary — maintenance had gone connection to legislator groups/individuals not central to largely unnoticed. at said, the price legislator’s re-election numerous human diseases, known as • Issues/projects on which legislator ciliopathies. of doing nothing would have been wishes to demonstrate leadership or • Issues/projects without clear associate with connection to congressional district much higher. constituents Considering the demonstrated Not important to importance of cilia for human Doing advocacy is like doing regu- lar maintenance on your car. It’s not health, many research groups have SOURCE: “THE CITIZEN’S HANDBOOK TO INFLUENCING ELECTED OFFICIALS.” sought to characterize the molecular cheap, and at times it’s frustrating, mechanisms of cilia biogenesis and but not taking the time to do it can your car for thousands of miles with “When they observe a surpris- function. Recently, researchers at the result in catastrophic damage. When the “check engine” light on and then ingly large number of protesters, National Eye Institute identied a your day consists of managing your being surprised when the car breaks policymakers update their beliefs gene that plays an important role in lab, attending faculty meetings and down. about preferences and the policy they cilia development. writing grants (never mind family But you don’t have to take my choose to set,” the researchers found Patients with ciliopathies experi- and other outside-the-lab responsibil- word for it. (1). To put it more succinctly, the ence a range of e ects, and some ities), it may seem nearly impossible Congressional Management Foun- squeaky wheel does, in fact, get the ciliopathies are fatal. Bardet-Biedl to nd the time to call your represen- dation President and CEO Brad Fitch grease! and Joubert syndromes, for example, tative, write to your senator or attend has spent 25 years in Washington as Biomedical research is likely to be result in deafness, retinal degen- an event in the next town over. a journalist, congressional aide, con- supported regardless of political party, eration and kidney disease. Meckel But like regular maintenance sultant and college educator. In 2010, but legislators need to know that it syndrome, meanwhile, is a severe Previously published in Nature Communications IMAGE COURTESY OF SHOBI VELERI of your car, advocacy is critical to he wrote “e Citizen’s Handbook to is important to you, the constitu- ciliopathy, and most people aicted protecting your personal investment. Inuencing Elected Ocials.” In the ent. Together, we certainly can work by it die before or shortly after birth e team generated a Cc2d2a- CC2D2A in the formation and/or For every scientist who doesn’t make book, Fitch outlines in a simple chart harder to make sure our elected due to respiratory problems or kidney null allele in mice. Loss of Cc2d2a stabilization of subdistal appendages an e ort to talk to his or her ocials how legislators perceive issues. Issues ocials know that an issue like failure. resulted in embryonic lethality with to initiate the process of cilia biogen- about the importance of supporting that are important to constituents and scientic research is a priority for In post-mitotic cells, the primary defects in multiple organs associated esis. e ndings are of clinical and research, for example, there are liter- are consistent with a legislator’s values constituents. cilium originates from the mother with cilia biogenesis, consistent biological signicance, as they begin ally dozens of neighbors talking to are the issues that are most likely to Advocating is tiring, frustrating centriole, which functions as a basal with Meckel syndrome phenotypes. to elucidate the molecular basis of the ocials about their policy or funding cause the legislator to take action. and even, in some ways, costly. But it body. e mother centriole also Cilia were absent in the tissues of Cc2d2a mutations present in Meckel priorities. Sitting on the sidelines e Harvard University Kennedy works. And just like car maintenance, contains distal and subdistal append- mutant mice during early stages of syndrome. (because of perceived lack of time or School of Government did a study in ignoring it will result in the degrada- ages that are important for membrane development, and there was neither a very real lack of interest) and watch- 2013 to nd out if political protests tion of your investment. subdistal assembly nor microtubule Elizabeth Meier (meier.lizzie@ tethering and docking. gmail.com) is a third-year Ph.D. ing the National Institutes of Health’s matter and looked at the 2010 Tea Benjamin Corb (bcorb@asbmb. e NEI researchers, led by anchoring. student at Johns Hopkins School budget erode is the same as driving Party movement for evidence. org) is director of public affairs Anando Swaroop, zeroed in on the e researchers say the work, of Medicine, where she studies at ASBMB. gene Cc2d2a, mutations in which are published in the journal Nature, bacterial cell division in Erin REFERENCE associated with Meckel syndrome. demonstrates an essential role for Goley’s lab. 1. http://www.hks.harvard.edu/fs/dyanagi/Research/TeaParty_Protests.pdf

8 ASBMB TODAY SEPTEMBER 2014 SEPTEMBER 2014 ASBMB TODAY 9 NEWS

Predicting adverse interactions between drugs is dicult; screening all pos- Sheila Sadeghi sible combinations in model organisms would be prohibitively expensive and received her Tabor time-consuming. However, one major known source of toxicity is inhibition award at the 20th New JBC/Herb Tabor Young International Sympo- of the liver enzyme cytochrome P450, which catalyzes the metabolism and sium on Microsomes clearance of many drugs. and Drug Oxidations Because P450 is a redox enzyme, its activity is dicult to study outside of in Stuttgart, Investigator Award winners its complex biochemical context; however, Sadeghi and her colleagues used a Germany. JBC Associate Editor F. solid electrode surface to immobilize P450 and characterize its catalytic rate Peter Guengerich of By Laurel Oldach in the presence of individual or combinations of drugs. is technology Vanderbilt University gives a way to predict exactly how two drugs metabolized by P450 will issued the award. interact with one another and prevent patients from being prescribed deadly Andrew DeVilbiss combinations. In the long term, Sadeghi envisions her work leading to high-throughput tests of drug–drug and food–drug interac- Andrew DeVilbiss, a doctoral stu- tions and also applications that may use polymorphic P450 variants better to individualize treatment regimens. dent in the cellular and molecular pathology graduate program at the University of Wisconsin Gopal Gunanathan Jayaraj School of Medicine and Public Gopal Gunanathan Jayaraj, a doc- Health, received a Journal of Bio- toral student at the CSIR-Insti- logical Chemistry/Herbert Tabor tute of Genomics and Integrative Young Investigator Award for his Biology in India, received a Tabor work on transcriptional control of award for his work illuminating erythropoiesis, the development the reasons that aminoglycoside of red blood cells. antibiotics, such as the tuberculo- Many changes must occur sis drug streptomycin, occasion- for a hematopoietic stem cell to ally damage patients’ hearing for become a red blood cell, including life. removal of the nucleus, alterations Jayaraj was studying a previ- to the cytoskeleton and changes ously described e ect of strepto- in the expression level of the mycin on microRNAs, a category globin genes, heme biosynthesis of small, noncoding RNAs that genes and many other genes. e a ect the translation of specic master agent of this change is the target genes. His colleagues transcription factor GATA-1. had shown that streptomycin Andrew DeVilbiss received his Tabor award at the Midwest Chromatin and Epigenetics meeting in Madison, Wis., in DeVilbiss described a new May. JBC Associate Editor John Denu of the University of Wisconsin–Madison issued the award. could bind to pre-microRNA21, interaction between the transcrip- preventing the microRNA from tion factor and a chromatin-modifying enzyme with the exciting additional discovery that the interaction was context- being completely processed and dependent. at is, GATA-1 required the chromatin-modifying enzyme to repress some but not all of its target a ecting cells’ ability to express genes. microRNA21 targets. Gopal Gunanathan Jayaraj received his Tabor award at the International Conference on Chemical Biology – Disease Mechanisms and Therapeutics in Hyderabad in February. JBC Associate Editor Ruma Banerjee of the University of Moreover, the e ects of the chromatin-modifying enzyme in combination with other known regulators of GATA When he followed up with a Michigan issued the award. function were variable: Some of the shared target genes also were sensitive to a second and/or third coregulator, while microRNA-wide screen to deter- others were not. mine whether this e ect extended beyond miRNA21, Jayaraj found that a large cluster of hearing-related micro- It previously had been thought that GATA factors mediate transcription using a common cohort of co-regulators RNAs also was a ected. Jayaraj characterized these interactions biochemically and further showed that streptomycin at the majority of target genes. However, DeVilbiss and his coworkers found a more intricate mechanism whereby could repress these microRNAs in a zebrash system in vivo, o ering a tantalizing, though partial, possible explanation transcriptional repression by GATA-1 is dependent on di erent combinations of co-regulators at di erent target for the antibiotic’s toxic side e ects. genes. Jayaraj adds that “this study also warrants a cautionary re-evaluation of other RNA-binding drugs for their o -target Of his future work, DeVilbiss says, “I am now interested in identifying the unique molecular attributes of (GATA-1 e ects in the context of miRNA and other functional noncoding RNA.” regulated) loci that mandate di erent coregulator requirements for repression.” Laurel Oldach (loldach1@jhmi. Sheila Sadeghi To learn more about the JBC/Herb Tabor edu) earned a B.A. in biology from Reed College and is pursuing a Sheila Sadeghi, a lecturer at the University of Torino in Italy, was honored with a Tabor award for her work on devel- Young Investigator award program, visit Ph.D. in biological chemistry at oping a testing platform for toxic interactions between small molecules that are known to be safe when administered http://www.jbc.org/site/home/tabor_award. Johns Hopkins University School individually. of Medicine.

10 ASBMB TODAY SEPTEMBER 2014 SEPTEMBER 2014 ASBMB TODAY 11 RETROSPECTIVE

endeavors there, publishing another hope of one day getting close enough to Africa in search of the Mokele- half a dozen or so virology papers to Nessie to obtain a tissue sample. mbembe, thought to be something Roy P. Mackal, 1935 – 2013 through 1971. But at the same time, Mackal described in a 1981 People like a living dinosaur of the smallish he was becoming more involved magazine interview the moment sauropod variety. He and his team Biochemist-turned-cryptozoologist hunted and more prominent in the eld of when he saw Nessie himself. It was talked to pygmy locals who reported cryptozoology. 1970, and the creature was just 30 sightings of the long-necked and Loch Ness monster and other mysterious beasts Brody recalls: “Cryptozoology – yards away, he told the magazine. He -tailed creature in Congo’s Likouala the term didn’t yet exist – was already saw “the back of the animal, rising swamps. By Angela Hopp strong, and he used to explain to us eight feet out of the water, rolling, Around that time, Mackal and paleozoology and the probability of twisting. If that’s a sh, I thought, others founded the International nding coelacanth-like, supposed- it’s a mighty sh indeed! To this day, Society for Cryptozoology at the oy P. Mackal, a retired associate to get lysogenic E.coli to produce extinct species. His reading was deep, when someone asks me, ‘Do you Smithsonian’s National Museum professor at the University of phage was to UV irradiate Petri plates and he knew this was not a eld that believe there is a monster in Loch of Natural History. He served as its R Chicago who began his career growing the bacteria, scrape the plate was going to please his peers.” But Ness?’ my stomach does a somersault. vice-president until the society was studying the biochemistry of bacte- and isolate the induced phage. Roy “Roy’s approach to cryptozoology was I know what I saw.” dissolved in 1998. riophage infection but who ended invented and then built a machine to scientic,” Brody said. “He studied In 1976, Mackal published the “Over the years, I saw Roy from up dedicating most of his life to the increase the amount of phage by 100 the subject assiduously and knew that rst of three books about hidden ani- time to time. He stayed calm and search for creatures that may or may fold. He grew the lysogenic bacte- nding positive results would be dif- mals, “e Monsters of Loch Ness.” philosophical about his choices, and I not exist, died Sept. 13, 2013. He ria in 10-liter asks, pumped them cult, even unlikely, but he thought According to a tribute by Loren Cole- never heard him complain one time” was 88. through quartz tubing surrounded the risk was worth taking, because he man, founder of the International about how his work was viewed by Mackal had been a public face by UV lamps and then incubated was passionate about the subject.” Cryptozoology Museum in Portland, some of his peers and administrators, in the 1980s for the often-ridiculed the irradiated bacteria until lysis While still employed by the Maine, Mackal “theorized that a Brody said. “He was one of the most but undeniably fascinating eld of occurred.” university, Mackal took the post of population of large invertebrate living interesting people I’ve ever known.” cryptozoology – that is, the study of Bob Haselkorn, another former scientic director of the Loch Ness fossils were living in the loch” but hidden animals. From the late 1960s colleague at Chicago, also remembers Angela Hopp ([email protected]) Investigation Bureau, which he held “later changed his mind and proposed is editor of ASBMB Today. to the mid-1970s, he served as scien- IMAGE COURTESY OF UNIVERSITY OF CHICAGO PHOTOGRAPHIC Mackal as an “imaginative” young sci- until 1975. e bureau employed that the creatures were zeuglodons, tic director for an institute formed ARCHIVE, [APF1-04046], SPECIAL COLLECTIONS RESEARCH CENTER, entist. In one project, Haselkorn says, UNIVERSITY OF CHICAGO LIBRARY sonar and a biopsy harpoon that ancient serpentine whales.” to research the Loch Ness monster (or Mackal and his group took phage Mackal himself had fashioned on the In the 1980s, Mackal went twice monsters) in the Scotland highlands, logical Chemistry in 1954. Mackal extracts from cells and observed what and he later spent time in the swamps ended up joining the lab of Kozlo ’s was at the time thought to be replica- of Congo, following up on alleged collaborator, Earl Evans. His next tion. Many years later, a di erent sightings of the elusive Mokele- four papers, with Evans, appeared in group armed with new technologies mbembe, which is believed by some the JBC between 1958 and 1964. and knowledge used “well-dened to be a living dinosaur. As former colleague Ed Brody mutants blocked at various steps in In memoriam Mackal was born in 1925 in Mil- recalls, by the summer of 1960, the assembly of heads, tails and tail waukee. His son, Paul Mackal, told Mackal was practically running the bers” and worked out the assembly By Mariana Figuera–Losada and Sapeck Agrawal the Chicago Sun-Times in Decem- Evans lab. “Roy was intelligent, knew pathways. ber that his father enjoyed reading a lot of biochemistry and biophysics, Mackal “could have scooped the books as a child about adventure and and was a wonderful, patient teacher assembly story by decades if he had Thomas C. Alber disparate elds and to extract funda- ogy from the Massachusetts Institute lost worlds, including Jules Verne’s of laboratory techniques,” says Brody, understood the use of mutants and omas C. mental insights from complex data of Technology in 1981. “20,000 Leagues Under the Sea.” A now chief medical ocer emeritus at invested the years it took to isolate Alber, 60, sets,” Susan Marqusee, a longtime Alber went on to develop inno- colleague who worked with him in SomaLogic Inc. “I never saw him or and characterize them,” Haselkorn a structural friend and colleague at Berkeley, vative computational methods to Chicago described him as “a heard him get angry, which would says. biologist and said in a statement. “In addition to uncover alternative protein structures romantic.” have scared a lot of people. He was an He quips that Mackal “was always professor of his impact on science, he’ll be remem- with potential biological function After serving in the military during ex-Marine and physically imposing.” an adventurer, pretty weak on molecular and bered for his scientic integrity, colle- from existing X-ray data. He discov- World War II, Mackal enrolled at Brody remembers Mackal as a controls.” cell biology at gial spirit, mentorship and intellectual ered a sophisticated system of protein the University of Chicago, earning a “master craftsman” who made instru- Mackal discovered his true calling ALBER the University enjoyment of collaborations.” communication within Mycobacte- bachelor’s degree in 1949 and a Ph.D. ments for various labs. “If he was in 1965 while vacationing in Scot- of California, Berkeley, died March Born in Japan, Alber was raised rium tuberculosis and found potential in biochemistry in 1953 under the not in his oce, he usually could be land. ere he came upon members 28 after ve-year battle with Lou in Southern California and earned targets against both tuberculosis and direction of Lloyd Kozlo , whose lab found in the machine shop,” Brody of the Loch Ness Investigation Gehrig’s disease. his B.S. in chemistry from UC Santa HIV. In 2013, e Protein Society focused on virus replication. “e fate says. Bureau conducting observations. He “He was known for his ability to Cruz. His rst scientic manuscript honored Alber with its Christian B. of bacteriophage T7,” Mackal’s rst He recalls working with bacterio- was hooked. He returned to Chicago span a wide range of scientic disci- was published in the journal Nature, paper, appeared in the Journal of Bio- phage lambda: “e standard method and continued to contribute to the plines, to see connections between and he then earned his Ph.D. in biol- CONTINUED ON PAGE 14

12 ASBMB TODAY SEPTEMBER 2014 SEPTEMBER 2014 ASBMB TODAY 13 CONTINUED FROM PAGE 13 of numerous potential drugs and Friedmann grew up in India and University and this led to the development of Colleagues and friends recalled vaccines. completed high school in 1943. In in 1942 and new therapeutic antibodies directed him as the author of numerous papers Annsen Award in recognition of Barbas received many awards in 1947, he earned his B.S. in chemis- a Ph.D. in against the EphA3 receptor. One such in leading scientic journals, a trusted “his foundational studies yielding an recognition of his contributions. try at the University of Madras and biochemis- antibody, KB004, is in phase II trials counselor to students and a nature understanding of the structure/func- He was a fellow of the American stayed to continue his research on try from the in patients with leukemia. In 2010, enthusiast. tion relationship of proteins.” Association for the Advancement enzymes in the university’s biochem- University his proposed research on KB004 was Alber, the founding director of the of Science and of the Academy istry labs while also earning his M.S. of Rochester acknowledged as one of the 10 best Marian Swendseid HEFTMANN Henry Wheeler Center for Emerging of Microbiology. He also was the In 1954, Friedmann won accep- in 1947. He research projects of the year by the Marian and Neglected Diseases, was a faculty founder of CovX Pharmaceuticals tance and a scholarship to a Ph.D. worked at the National Institutes of Australian National Health and Medi- Swendseid, a aliate in the California Institute (acquired by Pzer) and Zyngeni and program at the University of Chicago. Health from 1948 until 1963, when cal Research Council. prolic and for Quantitative Biosciences and a a co-founder of Prolifaron (acquired He conducted his thesis research with he joined the California Institute of Lackmann was born March 11, distinguished member of the Lawrence Berkeley by Alexion). Birgit Vennesland and completed his Technology. He then worked as a 1956, in Germany, where he grew up nutrition National Laboratory division of Ph.D. in 1958. For the next year, he research chemist at the U.S. Depart- with an anity for medicine. After scientist at the physical biosciences. Herbert C. Friedmann worked as a research associate at the ment of Agriculture in California from completing his B.S. in biochemistry University of UC Berkeley has established a Herbert C. university and subsequently moved 1969 until his retirement in 1983. at University of Hamburg, he moved SWENDSEID California, memorial fund in Alber’s memory. Friedmann, to Baltimore to complete a two-year Heftmann used chromatography to Australia to pursue a Ph.D. in Los Angeles, Fielding School of Pub- It will sponsor an annual lecture on a pioneer fellowship at the Johns Hopkins Uni- to study the role of steroids in plant immunology at the University of Syd- lic Health, passed away on Jan. 19 at infectious disease. Find out more at in bacte- versity, where he met his future wife, biology and was the rst to show the ney, which he completed in 1992. age 95 in Irvine, Calif. She had been bit.ly/TomAlberFund. rial enzymes Joan Bowerman. presence of cholesterol in plants. In For his postdoctoral studies, Lack- an ASBMB member for 64 years. research, In 1960, Friedmann returned to 1961, he developed a precursor to mann chose the Walter and Eliza Hall Swendseid was born Aug. 2, 1918, Carlos Barbas III devoted and Chicago as an assistant professor in high-pressure liquid chromatography Institute of Medical Research in Mel- in Petersburg, N.D. She earned a B.S. Carlos Barbas FRIEDMANN enthusiastic physiology and began his extensive instruments. bourne and later the Ludwig Institute in chemistry and M.S. in organic III, an organic educator to budding scientists, and studies of vitamin B12 and its role in During his career, Heftmann for Cancer Research. ere, with chemistry at the University of North and biologi- passionate storyteller on the subjects bacterial nucleotide synthesis. He was published nearly 200 articles and mentorship from the then-director of Dakota and a Ph.D. in biological cal chemist at of biology, history and literature, died later promoted to associate professor. two books, including six editions the institute, Tony Burgess, Lack- chemistry at the University of Min- e Scripps Jan. 13. He was 86. In a university statement, Donald of “Chromatography,” which has mann established his own laboratory nesota in 1941. Research Along with having served the Uni- Steiner, a former chairman of bio- become a standard reference. He was in 2000 with a focus on translational Swendseid pioneered research Institute, died versity of Chicago for almost 50 years chemistry and molecular biology at symposium editor of the Journal of cancer research. In 2003, Lackmann on protein, choline, folic acid and BARBAS from a rare with excellent teaching and research, Chicago, described Friedmann as “one Chromatography from 1982 to 2008, moved his research program to the vitamin B12 metabolism, identied form of medullary thyroid cancer on Friedmann was known for his book of the department’s best citizens.” handling almost 5,000 papers. Monash University biochemistry and histidine as an essential amino acid June 24. Barbas was the Janet and “Enzymes,” an article he co-wrote Steiner also added, “He gave more molecular biology department, where for adults and published more than Keith Kellogg II chair professor and on the life of eodor Escherich lectures than anyone else. He intro- Martin Lackmann he made highly signicant discover- 150 manuscripts. She served as an a member of e Skaggs Institute (the researcher after whom E. coli duced undergraduates to biochemistry Martin Lack- ies regarding Eph receptor signaling associate editor of e American for Chemical Biology at TSRI in San was named), and a short paper titled in a way that made it special.” mann, a lead- and function and identied several Journal of Clinical Nutrition. Diego. “Fifty-six laws of good teaching,” a For his exceptional undergraduate ing German- molecular targets for the develop- A scholarship fund to support Barbas was born Nov. 5, 1964, in guide for any instructor. One of his teaching abilities, Friedmann won in Australian ment of antibody-based anticancer students or investigators focused St. Petersburg, Fla. He received a B.S. laws was “Never expect your students 1978 the coveted Llewellyn John and biochemist therapeutics. Before his death, he in the area of nutrition and cancer in chemistry at Eckerd College in to learn or understand anything that Harriet Manchester Quantrell Award and associate was working on a patented antibody prevention was established with Florida and earned a Ph.D. in organic you cannot or did not learn or under- for Excellence. Until his retirement in professor at targeting ADAM-10, which is in the the American Society for Nutrition chemistry at Texas A&M University stand yourself.” 2009 at the age of 82, he continued to LACKMANN Monash Uni- preclinical development phase. Foundation in memory of Swend- in 1989. He then did postdoctoral Friedmann was born June receive glowing reviews from students. versity who had been spearheading seid. More information is available at work, rst at Pennsylvania State 19, 1927, to a Jewish family in the discovery of several novel drugs Fabian Lionetti www.nutrition.org. University with Steven Benkovic and Mannheim, Germany. His mother Erich Heftmann against cancer, died suddenly on May Fabian “Doc” J. Lionetti, professor later at Scripps with Richard Lerner. was a violinist and his father a physi- Erich Heftmann, a chemist well 22. Lackmann made major contribu- of biochemistry at Boston University Mariana Figuera-Losada ([email protected]) is a He joined TSRI in 1991 and com- cian. At age 11, his childhood took known in the chromatography world, tions to our understanding of how Medical School, died on March 14 at postdoctoral fellow at the Johns bined molecular biology, chemistry an unfortunate turn when his father died Jan. 18 at his home in Walnut a family of cell-signaling receptors age 96. Hopkins University. She wrote the and medicine to study asymmetric was arrested for being Jewish and Creek, Calif., at age 95. known as the Eph family of receptor Fabian, who held a Ph.D. in physi- briefs on Alber, Barbas, Heftmann, catalysis, zinc nger technology, the family residence was ravaged by Heftmann was born in 1918 in tyrosine kinases regulates cell–cell cal chemistry from Rensselaer Poly- Lionetti and Swendseid. Sapeck Agrawal (sapeck.srivastava@ synthetic antibodies and proteinlike members and sympathizers of the Vienna, Austria, and studied medicine interactions during normal develop- technic Institute, was a distinguished gmail.com) recently earned her DNA enzymes. He developed the Nazi party. However, after agreeing to there till 1938. He immigrated to the ment and cancer. researcher whose body of work Ph.D. in molecular microbiol- rst human antibody phage libraries give up their property, the family was U.S. in 1939 after the annexation of More recently, he was committed contributed to advances at NASA, the ogy and immunology from the and synthetic antibodies. His research permitted to immigrate to Madras Austria by Nazi Germany. He earned to exploiting this new knowledge to U.S. Department of Energy and the Johns Hopkins University. She wrote the briefs on Friedmann and Lackmann. has contributed to the development (now Chennai, India) in 1939. a B.A. in chemistry from New York develop treatments for cancer patients, eld of blood preservation.

14 ASBMB TODAY SEPTEMBER 2014 SEPTEMBER 2014 ASBMB TODAY 15 JOURNAL NEWS

Thematic series on caloric restriction and ketogenic diets By Mary L. Chang

e September issue of the Journal raising sugar levels in the blood. Lindsey B. Gano, Manisha Patel of Lipid Research marks the begin- Because a ketogenic diet minimizes and Jong M. Rho ning of a new thematic review series the intake of carbohydrates while also The collective therapeutic potential examining how diet modications increasing fat intake, sugar levels in of cerebral ketone metabolism improve general health and manage a the blood are lowered, and the liver in traumatic brain injury broad range of chronic diseases. is able to take fat consumed and Mayumi Prins and Joyce Matsumoto Caloric restriction, a type of produce ketone bodies, which are The ketogenic diet for the treatment The adult Hawaiian bobtail squid with inset scale IMAGE COURTESY OF WIKIMEDIA COMMONS USER MARGARET-MCFALL NGAI controlled therapeutic fasting, released into the bloodstream. As the of malignant glioma reduces oxidative stress and dam- ketones are taken up by cells of the Eric C. Woolf and Adrienne C. Scheck investigators used two quantitative present at the light organ. bacterium’s adhesion to the squid’s body, cells break down the ketones age while promoting more ecient Editorial board member omas proteomic techniques to compare a From the investigators’ analyses of light organ. energy metabolism. Ketogenic diets instead of sugar for energy, a process N. Seyfried of Boston College is coor- set of special cells taken from squid the di erences in protein expression “A growing body of evidence from — characterized by low carbohy- called ketosis. dinating the series. In 2012, Seyfried colonized with bacteria and those that in hemocytes taken from colonized a variety of animal model systems drate, sucient protein and high fat e following JLR reviews address published the textbook “Cancer as a were uncolonized. “is is the rst and uncolonized squid, they saw suggests that benecial microbes intake — have been used primarily to this subject: Metabolic Disease: On the Origin, time that two independent, high- that the presence of V. scheri in the inuence a host’s innate immune sys- manage seizures in epileptic children. Ketone body therapy: from ketogenic diet Management, and Prevention of throughput proteomic techniques light organ induced changes in the tem to foster these associations,” says However, more recently, these diets to oral administration of ketone ester Cancer,” which presented methodol- have been applied to the squid– hemocyte proteome to promote the Nyholm. Because macrophagelike have shown promise, along with Sami A. Hashim and eodore VanItallie ogy and ndings of the sources and Vibrio association,” says Spencer cell’s tolerance of the bacteria and cells similar to hemocytes are found drugs and hyperbaric oxygen therapy, Ketone ester effects on metabolism prevention of cancer. Nyholm, also at the University of favor symbiosis. e changes involved in almost all animals, he adds, “our in managing cancer, and they may and transcription Connecticut and the senior author on the cytoskeleton, lysosome function, study may provide insight into other have applications in managing certain Mary L. Chang (mchang@asbmb. Richard Veech org) is publications manager for the paper. proteases and receptors. Because host–microbe associations.” neurological diseases. ASBMB. e cells the investigators chose scientists still don’t understand the After they are consumed, carbo- Ketogenic diets, mitochondria to look at are hemocytes, which are precise mechanisms that contribute Rajendrani Mukhopadhyay hydrates are broken down to glucose, and neurological diseases ([email protected]) blood cells in the squid’s light organ; to host–symbiont specicity, the is the senior science writer and these cells have properties of the investigators are now focusing on blogger for ASBMB. Follow her immune system’s macrophages and studying several proteins identied in on Twitter at www.twitter.com/ interact with the symbiotic bacteria this study that appear to inuence the rajmukhop. How a squid forms a relationship with a bacterium By Rajendrani Mukhopadhyay

How do you get into a mutually has a light organ that is exclusively develop. “Our lab is interested in Thematic series on phospholipase D and cancer benecial relationship? at is the colonized by V. scheri. e squid understanding the role of the host’s By Indumathi Sridharan question researchers asked in a recent feeds the bacterium a solution of innate immune system in establish- paper in the journal Molecular & sugar and amino acids and, in return ing specicity,” says Tyler Schleicher A new thematic minireview series in inammatory diseases, and regulation tion, cell adhesion and proliferation. Cellular Proteomics, albeit for a for the steady food supply, the bac- at the University of Connecticut, the the Journal of Biological Chem- of levels of the signaling metabolite, In light of these activities, PLD has a squid and its bacterial partner. e terium gives o the light that masks rst author on the MCP paper. “Each istry focuses on phospholipase D phosphatidic acid. A deeper under- direct impact on cancer growth, inva- researchers showed that in order for the squid’s silhouette while it goes generation of squid is colonized by V. and its role in cancer. PLD signaling standing of PLD has broad applica- sion and metastasis and is therefore the Hawaiian bobtail squid to form a hunting for various species of shrimp scheri from the environment, and controls a variety of cellular activities tions in developing targeted drug a therapeutic target in cancer treat- symbiotic relationship with the biolu- for its own meals. they must distinguish between the (namely, proliferation, migration and therapies for cancer. ments. e author points out recent minescent Vibrio scheri, proteomic Scientists study the squid and symbiont and a huge background of lipid metabolism) and thus plays a key In the rst article, Julian Gomez- developments in PLD research and changes have to occur in a set of cells its bacterial partner as a model to nonsymbiotic bacteria that are found role in cancer invasion and metastasis. Cambronero briey describes the their implications in cancer treat- of the squid. understand how benecial bacteria in seawater.” e question is how the e series highlights PLD’s tumori- various mammalian isoforms of PLD ments. For example, combining radia- form associations with multicel- squid achieves this feat. e Hawaiian bobtail squid, for- genic potential, tools to study its and discusses mechanisms by which lular organisms and help animals To answer the question, the mally known as Euprymna scolopes, in-vivo function, its putative role in PLD1 and PLD2 a ect cell migra- CONTINUED ON PAGE 18

16 ASBMB TODAY SEPTEMBER 2014 SEPTEMBER 2014 ASBMB TODAY 17 CONTINUED FROM PAGE 17 activity in cancer, the use of PLD- caused by a misfolded protein devoid to be prionlike diseases, and predict provide therapeutic benets. Studies selective inhibitors and microRNA of a genomic component — has been that the next generation of research evaluating potential therapies target tion with PLD-inhibitor drugs is an for cancer therapeutics, amplication proved. e new dogma that resulted may rely on transgenic rats. Rats may secretion, clearance or uptake of tau e ective strategy to treat chemother- of PLD expression resulting from has been fruitful for guiding new be better suited for studying human aggregates. apy-resistant and radiation-resistant genomic alterations in PLD gene and approaches to studying Alzheimer’s neurological diseases because of their In the nal minireview in the cancer cells. e author concludes by dynamic control of PLD signaling by and Parkinson’s diseases. In addition, more complex behaviors and larger series, Giovanna R. Malucci, Mark specifying the challenges remaining transcription factors in cancer. e emerging biochemical details of the brain sizes. Halliday and Helois Radford examine in PLD research, such as dening the authors also discuss PLD regulation in pathogenesis of misfolded proteins Surachai Supattapone of the Geisel how prion generation and spread in-vivo mechanisms of PLD signaling various inammatory conditions and are beginning to provide potential School of Medicine at Dartmouth a ects neurotoxicity. Prion diseases, and establishing the crystal structure the mechanisms by which PLD-selec- targets for therapy. University summarizes, in the second including scrapie, Creutzfeld–Jakob of PLD. tive inhibitors, such as triptolide and In a new thematic minireview minireview, studies with synthetic Disease and bovine spongiform Yi Zhang and Michael Frohman rebamipide, exert antitumorigenic and series in the Journal of Biologi- prions and the enhancement of infec- encephalopathy (mad cow disease), in the second minireview discuss the anti-inammatory e ects. e authors cal Chemistry, Prusiner and other tivity with cofactors. Supattapone are transmissible and fatal. In these tools used to study the physiologi- emphasize that PLD-selective inhibi- researchers cover prion replication, writes, “Recently, synthetic prions diseases, prion protein is the infec- cal role of PLD1 within a tumor and tors have great therapeutic potential transmission and neurotoxicity. JBC with a high level of specic infectivity tious agent, and accumulation of its microenvironment. e authors for treating cancers and inammatory Associate Editor Paul Fraser of the have been produced from chemically prion aggregates leads directly to describe how small molecular inhibi- conditions. University of Toronto oversaw the dened components in vitro.” ese neurotoxicity and eventual death. In tors and cell lines were used to dene In the fourth and nal minireview, be an e ective therapeutic strategy for series. biochemical studies, he emphasizes, Alzheimer’s and Parkinson’s, other PLD’s function and PLD1’s role David Foster and colleagues high- cancer treatments. In the rst minireview, Joel C. provide formal proof that prions are proteins — including amyloid-beta, in cancer. However, these in-vitro light the intracellular regulation of In the introductory commentary Watts and Prusiner, both of UCSF, indeed infectious agents lacking a tau and alpha-synuclein — aggregate approaches su er from limited physi- phosphatidic acid and its implication for the collection, series organizers discuss the importance of mouse nucleic acid genome and elucidate and propagate throughout the brain; ological relevance. Alternatively, stud- in cancer-cell survival via mamma- Julian M. Gomez–Cambronero and models for studying pathogenesis the roles of the cofactor molecules — however, the spread of these mis- ies using animal models (particularly lian/mechanistic target of rapamycin, George M. Carman remark that, of prion diseases and developing such as phosphatidylenthanolamine folded protein aggregates is not linked PLD1-decient mice) provide better or mTOR, activity. e ability of despite the evident advances in PLD new therapies. Transgenic mice and RNA — in the propagation and clearly to neurodegeneration. Some insight into the in-vivo role of PLD1 mTOR to integrate nutrients and research, many issues need further that overexpress the prion protein, maintenance of infectious prions. studies using mouse models of scrapie in cell metabolism, tumorigenesis, growth-factor signals during cell- investigation. Realizing the full known as PrP, develop clinical signs Furthermore, Supattapone writes, have found a dissociation between angiogenesis, autophagic response cycle progression depends heavily potential of PLD inhibition in of disease in less than half the time cofactor molecules “inuence strain prion replication and neurotoxicity. and therapy resistance. e authors on intracellular phosphatidic acid cancer therapeutics requires a bet- it takes for normal mice. So-called properties by facilitating specic What is the relationship between also mention new techniques, such as levels. Phosphatidic acid is a signaling ter understanding of various PLD knock-in mice, in which the normal PrPSc conformations.” prion propagation and toxicity? e genetically encoded phosphatidic acid metabolite produced by three major isoforms, their role during cancer PrP gene is replaced with a mutant In the third minireview, Marc I. authors of this minireview focus on sensors and advanced intravital imag- metabolic sources: enzymatic action progression and the evaluation of PrP gene, have been used to study Diamond and Brandon Holmes of the unfolded protein response, “a ing, that can elucidate the impact of of PLD on phosphatidylcholine, the isoform-specic PLD inhibitors in pathogenesis of mutations associated Washington University in St. Louis protective cellular mechanism that PLD1 in early steps of tumor develop- diacylglycerol kinase pathway and the clinical trials. with sporadic and genetic human review the studies of the prionlike tau is induced during periods of cellular ment and metastasis. lysophosphatidic acid acyl transferase prion diseases. e authors review the protein associated with Alzheimer’s and endoplasmic reticulum stress, Dong Woo Kang and colleagues pathway. e authors discuss how Indumathi Sridharan (sridharan. drawbacks and limitations of using disease. Several proteins implicated in which aims to maintain protein-fold- focus on regulation of PLD expres- compensatory pathways maintain [email protected]) earned mouse models to study Alzheimer’s the development of Alzheimer’s have ing homeostasis with the ER.” era- sion and its implications in cancer and intracellular levels of phosphatidic her bachelor’s degree in bioin- and Parkinson’s diseases, considered been shown to aggregate and spread peutic manipulation of the unfolded inammation in the third minireview. acid when one pathway is compro- formatics in India. She holds a Ph.D. in molecular biochemistry to neighboring brain cells. Although protein response, the authors note, Cancerous phenotypes and inam- mised. Given mTOR’s dependency on from Illinois Institute of Technology, Chicago. She these proteins, notably tau and alpha appears to provide neuroprotection in matory diseases are characterized phosphatidic acid and strong mTOR did her postdoctoral work in bionanotechnology at synuclein, are distinctly di erent animal models. by aberrant PLD expression. In this activity in cancer cells, the authors Northwestern University and is now an intern at from prion protein, they can undergo article, the authors elaborate on the suggest that interfering with phospha- the Office of Technology Transfer at the National Institutes of Health. conformational changes leading to dysregulation of PLD expression and tidic acid metabolism could prove to Thomas E. Schindler (tschindler. aggregation and the formation of [email protected]) earned a Ph.D. brils in a prionlike manner. Sev- in immunology from the University eral recent studies have detected the of Illinois Medical Center in 1981. After a postdoctoral stint spread of tau aggregates between cells at Memorial Sloan–Kettering Cancer Center, in vivo and in vitro. e ability of tau he joined Xytronyx, a small biotech company in Thematic series on prions aggregates to move across synapses San Diego started by his graduate adviser, Peter could explain the involvement of Baram. He took a year off in 1992 to move back By omas E. Schindler east and become a high-school science teacher. neural networks in neurodegenerative Since early retirement from full-time teaching in diseases, the authors say, and inter- 2007, he has taught biology and microbiology in More than 30 years ago, Stanley “prion” and began to develop evi- Since then, the prion hypothesis ruption of the cell-to-cell propaga- nearby community colleges. Now he is pursuing a Prusiner at the University of Califor- dence to support his radical hypothe- — that scrapie, a fatal neurodegen- tion of protein aggregates could new career: science writing. nia, San Francisco, coined the term sis for a new kind of infectious agent. erative disease in sheep and goats, is

18 ASBMB TODAY SEPTEMBER 2014 SEPTEMBER 2014 ASBMB TODAY 19 LIPID NEWS

actin cytoskeleton abolished the shown that these gan- sphingolipid domains. e sizes of the gliosides form separate Our evolving view sphingolipid domains and their higher microdomains that are dependency on the cytoskeleton dependent on the actin than on cholesterol indicated these cytoskeleton (5). us, domains were not lipid rafts. microdomains consisting of plasma membrane domains After publishing our nding of di erent sphingolipid of sphingolipid domains (1), we species are present in the By Mary L. Kraft and Raehyun Kim returned to imaging cholesterol in plasma membrane, which parallel with sphingolipids. Again, we suggests an active, energy- Illustration of factors that may affect the formation of plasma- found that cholesterol was distributed dependent mechanism of membrane domains. e recently used a new chemi- membranes and the cholesterol-sensi- After conrming reproducibility, we fairly uniformly in the plasma mem- membrane organization. cal imaging technique to tive clustering of membrane proteins performed numerous control experi- brane and not enriched within the Given that many lipids plasma membrane and the intracellu- W visualize the distributions thought to reside in rafts. Yet domains ments that tested for a multitude of sphingolipid domains (2). is lack are signaling molecules or their pre- lar locations where the sca old protein of sphingolipids and cholesterol in enriched with cholesterol and sphin- potential artifacts. of cholesterol enrichment conrmed cursors (i.e., ceramide, diacylglycerol, resides. For instance, cholesterol bind- the plasma membranes of broblasts golipids had not been imaged directly We ruled out the possibilities that that the sphingolipid domains were lysophosphatidic acid) (9), cells likely ing to the NHERF1 sca old protein (1, 2). Our unexpected nding of in actual cell membranes, likely due to the micrometer-scale sphingolipid not lipid rafts. Of course, we cannot use active mechanisms to segregate regulates its co-localization with the cytoskeleton-dependent sphingolipid a “technical impasse” (4). Techniques domains we observed were induced rule out the possibility that we did each bioactive lipid class within the cystic brosis transmembrane conduc- domains that are not enriched with for imaging dynamic lipid domains by cell xation, the detection of excess not detect lipid rafts because they plasma membrane so that signaling tance regulator, known as CFTR, at cholesterol has led us to revise our that were smaller than the di raction lipid material due to vesicles or intra- are smaller than the 87-nm-lateral molecules are available when needed. the plasma membrane and NHERF1- views on plasma membrane domains. limit of light were not yet widespread. cellular membranes adjacent to the resolution we achieved. However, the Of course, further studies are required mediated CFTR activation (10). ough the plasma membrane Furthermore, cooperative interactions plasma membrane, cell topography, lack of cholesterol enrichment in the to assess the hypothetical existence of Likewise, oxysterol-binding protein may contain microdomains with a between cholesterol and sphingolipids nonspecically adsorbed labels and sphingolipid domains indicates cohe- domains of di erent bioactive lipids functions as a sca old protein that variety of di erent lipid compositions, might be perturbed by labeling them many other artifacts (1). We also con- sive cholesterol–sphingolipid inter- and to identify the mechanisms for requires cholesterol binding in order cholesterol- and sphingolipid-enriched with uorophores. rmed the existence of micron-scale actions contribute little to plasma- their formation. to complex with two phosphatases, microdomains, called lipid rafts, have To address this challenge, we were sphingolipid domains in the plasma membrane organization, which refutes Why do cholesterol levels a ect cell PP2A and HePTP, forming an assem- been the most intensely scrutinized. developing an approach that used a membrane by uorescence microscopy a major tenant of the raft hypothesis. function in the absence of cholesterol- bly involved in ERK signaling (11). Lipid rafts are dened as small, new surface-sensitive imaging mass- imaging of metabolically generated Our data argue against the exis- enriched plasma membrane domains? Cleary, much research is required to dynamic and ordered assemblies of spectrometry technique, high-resolu- uorescent sphingolipids in the mem- tence of lipid rafts within the plasma Emerging hypothetical mechanisms assess the roles of specic cholesterol- cholesterol, sphingolipids and proteins tion secondary ion mass spectrometry, branes of living broblast cells (1). membrane (7). Instead, our results of cholesterol-mediated cell function protein interactions in cholesterol– that may combine to form larger or SIMS, to visualize metabolically How could our nding of micron- support the model of plasma mem- involve modulation of protein activity sensitive cell function. structures (3). Rafts are postulated incorporated, stable isotope-labeled scale sphingolipid domains be correct brane organization in which cortical by direct cholesterol binding. Choles- Identifying the mechanisms that to regulate protein–protein interac- sphingolipids and cholesterol in the when it seemed to contradict so actin and its associated proteins divide terol binding/unbinding to sca old control lipid organization within the tions by laterally segregating proteins plasma membrane with ~100-nm lat- much previously reported data? Upon the plasma membrane into distinct protein is hypothesized to regulate the plasma membrane and the sources of according to their anity for ordered eral resolution. High-resolution SIMS reevaluating the literature, we found domains by establishing di usion bar- formation of a signaling complex and cholesterol-sensitive cellular processes membrane domains. Cell signaling is complementary to uorescence that the contradiction was not with riers that sustain concentration gradi- its function (10). will require a signicant number of and virus budding are among the pro- microscopy, because stable isotopes do previously reported data but instead ents produced by vesicle transport (8) e cholesterol-sensitive assembly new studies. We expect that new cesses that lipid rafts hypothetically not alter the chemical structure and with the conclusions that had been or lipid-modifying enzymes. of these signaling complexes could e orts to develop and test alternative mediate. is potential importance thus the interactions or tracking of inferred from the biophysical proper- Furthermore, the direct imaging be modulated by the di erence in hypotheses for lipid-mediated biologi- and the simplicity of the raft hypoth- the lipids they label, but it cannot be ties of putative raft components. e of GM1 and GM3 by others has the cholesterol concentrations in the cal function are critical to advanc- esis attracted us to the eld. performed on living cells. few reports in which sphingolipids ing our understanding of plasma ough membrane organization We obtained our rst images of were imaged directly showed that REFERENCES membrane domains and their roles in and function is now our focus, we the sphingolipid and cholesterol gangliosides form nanoscale domains cellular function. 1. Frisz, J.F. et al. Proc. Nat. Acad. Sci. U.S.A. 110, E613 – E622 (2013). entered this eld as a bioanalytical distribution in the plasma membranes (5) but that sphingomyelin forms 2. Frisz, J.F. et al. J. Biol. Chem. 288, 16855 – 16861 (2013). laboratory that was developing of broblast cells in 2009. To our membrane domains with dimensions Mary L. Kraft (mlkraft@illinois. 3. Lingwood, D. et al. Science 327, 46 – 50 (2010). edu) is an associate professor new methods to obtain chemical surprise, we saw sphingolipid domains similar to those we observed (6). 4. Jacobson, K. et al. Nat. Cell Biol. 9, 7 – 14 (2007). in the chemical and biomo- information from biointerfaces with that were too large to be lipid rafts We next probed the mechanisms 5. Fujita, A. et al. Biochim. Biophys. Acta – Mol. Cell Biol. Lipids 1791, 388 – 396 (2009). lecular engineering department at the University of Illinois, submicron lateral resolution. At and a relatively uniform cholesterol responsible for these sphingolipid 6. Tyteca, D. et al. Biochim. Biophys. Acta 1798, 909 – 927 (2010). the time, the raft hypothesis was distribution within the plasma mem- domains. We found that the abun- Urbana-Champaign. Raehyun 7. Kraft, M.L. Mol. Biol. Cell 24, 2765 – 2768 (2013). Kim ([email protected]) is a supported strongly by indirect data, branes of mouse broblast cells. Baf- dances of the sphingolipid domains in 8. Kusumi, A. et al. Annu. Rev. Biophys. Biomol. Struct. 34, 351 – 378 (2005). graduate student in the chemical including the spontaneous formation ed by these results, we spent the next the plasma membrane were reduced 9. Wymann, M.P. et al. Nat. Rev. Mol. Cell Biol. 9, 162 – 176 (2008). and biomolecular engineering of ordered cholesterol- and sphin- few years optimizing our approach by depletion of cellular cholesterol. 10. Sheng, R. et al. Nat. Commun. 3, 1249 (2012). department at the University of Illinois, Urbana-Champaign. golipid-enriched domains in model for imaging sphingolipid distribution. However, depolymerization of the 11. Wang, P.-Y. et al. Science 307, 1472 – 1476 (2005).

20 ASBMB TODAY SEPTEMBER 2014 SEPTEMBER 2014 ASBMB TODAY 21 ANNUAL MEETING

Dear readers, DNA replication and repair now can the science covered. Held in con- be visualized in the act through the junction with Experimental Biology We invite you to attend the exciting application of super-resolution tech- 2015, the ASBMB sessions and events 2015 annual meeting of the American niques. e scientic programming represent an unrivaled opportunity Society of Biochemistry and Molecu- showcases molecular-level studies of to learn about the latest discoveries lar Biology that will be held from complex processes using the newest in the range of subdisciplines that fall March 28 through April 1 in Boston. tools. under the biochemistry and molecular e 14 themes of the meeting Also, we are pleased to return to biology umbrellas. Your participation cover the broad range of biomolecules the tradition of hosting morning will be rewarded with exposure to new and systems that interest the ASBMB plenary sessions by eminent scientists. science, the chance to establish col- membership. We are certain that you See the list of plenary lecturers and laborations and network, and access to will nd new twists in the recent dis- their tentative talk titles on page 26. mentoring and career advice. coveries as well as new areas in which e programming will incorporate You will nd, as you read the the science is advancing rapidly. short platform presentations selected theme summaries provided in the Recurring themes include over- from the submitted poster abstracts. following pages, that the meeting turning paradigms (such as the uid Each scientic theme will sponsor a provides great science for all — new mosaic model for membranes and poster competition with cash awards approaches and new systems. Submit the assumption that protein structure for the winners. your abstracts today, and prepare is necessary for function) and expand- Undergraduate and graduate yourselves to hear about the latest ing dogmas (such as DNA codes for students and postdoctoral fellows exciting advances in biochemistry and RNA, which codes for protein) to are encouraged to apply for generous molecular biology! show the beautifully orchestrated travel awards. Please check the guide- complexity of biological processes. lines, and apply if you are eligible, See you in Boston! In transcription and translation, at http://asbmb.org/meetings/ Dorothy Beckett, this involves RNA and chromatin annualmeeting2015/travelaward/. University of Maryland, modications and modes of crosstalk. A unique feature of the ASBMB and Mary Roberts, e same level of crosstalk between annual meeting is the breadth of Boston College

CANCER: THE WAR AT 44, WARBURG AT 90 Has the tide turned? In this issue: In the October issue: By Neal Fedarko 23 Invitation from meeting chairs Molecular mechanisms of infection and immunity On Dec. 23, 1971, the National e sessions will focus on four arenas Lipids: in vivo dynamics, protein partners and signaling “The future ain’t 23 Cancer: The war at 44, Warburg at 90 Cancer Act was signed into law, that have signicantly impacted What’s new in membrane transport proteins beginning what has been called diagnosis, prognosis and treatment what it used to be.” 24 DNA replication and repair America’s War on Cancer. Since then, strategies. Plant metabolism e second session will bring we have developed an understand- the young and dynamic elds of 24 Protein nonfolding as a regulatory phenomenon Mechanistic impacts of post-translation modifications ing of cancer as a cluster of more “You can observe a lot microRNA and long noncoding than 200 diseases characterized by RNA into focus in modulating tumor 25 Extracellular matrices in health and disease RNA expression and post-transcriptional regulatory events just by watching.” unrestrained growth and spread of survival, metastasis and crosstalk with The human microbiome abnormal cells locally, regionally or at Where is it? Is treatment necessary? other cells in the microenvironment. 26 New directions in enzymology Microbiome dynamics and health disparities a distance, with variable aggressive- How can we target it? Which therapy ness. Despite this daunting complex- will work? Plenary lectures “Déjà vu all over again.” 26 Careers, mentoring and changes in medical education ity and heterogeneity, we are in an e rst session will cover novel era of optimism. is ASBMB imaging techniques, reagents and More than 90 years ago, Otto Hein- annual meeting symposium will their application to detection, rich Warburg demonstrated that, provide an update on the theater of treatment and subsequent surveil- operation 44 years on in the war. lance. CONTINUED ON PAGE 24

22 ASBMB TODAY SEPTEMBER 2014 SEPTEMBER 2014 ASBMB TODAY 23 CONTINUED FROM PAGE 23 “It ain’t over till it’s over.” e quotes above are from Law- Flexible recognition many human diseases. Although the ing clear connections between bio- rence Peter “Yogi” Berra, who also loss of native, functional interactions logical function and native disorder. under normal conditions, tumor e idea of stimulating the immune said, “It’s tough to make predictions, of binding partners of the disordered proteins is thought cells, unlike normal cells, use aerobic system to ght o cancer has been especially about the future.” Disordered regions in proteins fre- to play an important role in disease Trying to hit glycolysis for energy metabolism. around for more than 120 years. quently mediate contacts with other development, these native functions Modern metabolomics has led to Advances in biologics — antibodies, a moving target ORGANIZER: Neal Fedarko, Johns proteins or nucleic acids. Reports that are poorly understood. e second a ner understanding of energy inhibitors and immune cell stimula- Hopkins University School of partially ordered linear motifs embed- session will explore the mechanisms e prevalence and functional signi- metabolism in tumor cells and of tion/modulation — suggest that the Medicine ded within disordered sequences of native functions of disordered cance of protein disorder are rmly therapeutic targets specic for tumor potential of immunotherapy nally is participate in these binding events proteins implicated in amyloidogenic established, but can this knowledge cells. being realized. are ubiquitous; so are observations of neurodegenerative disease. be translated into practical medical coupled folding and binding. Even intervention? In the nal session, so, is folding required for binding? What does it mean we explore recent advances toward directly targeting disordered proteins is session will cover the binding to be disordered? DNA REPLICATION AND REPAIR mechanisms employed by intrinsi- with small-molecule therapeutics. cally disordered proteins. e absence of a cooperatively folded native state provides a negative deni- ORGANIZERS: Cellular systems for repair Elizabeth What makes a good tion for disorder but provides no Rhoades, Yale By Michael G. Fried and Myron F. Goodman insight into the diversity of natively University, and protein go bad? disordered states. e third session Scott Showalter, Pennsylvania State University In their 1953 paper describing the systems and the mechanisms by that allow repair processes to accom- Disordered proteins are implicated in will cover recent advances establish- structure of B-DNA, Francis Crick which they operate. modate them. and James D. Watson recognized e rst session will give a perspec- Replication and repair complexes that noncanonical base pairs could be tive on structural and biochemical often contain many components that sources of mutations. As most muta- mechanisms of aberrant translesion interact, sometimes over large physi- EXTRACELLULAR MATRICES IN HEALTH AND DISEASE tions are deleterious, the repair of DNA replication. cal distances. e fourth session will aberrant DNA structures is an essen- Structural insights into replication explore the roles of cooperativity in tial cellular process. More recently, delity and mismatch repair will be the function and regulation of these What is a matrix? a vibrant eld of research has grown explored in the second session, as will complexes. By Je Gorski and Karen Lyons around the discovery and character- super-resolution live cell-imaging ization of cellular systems that repair studies that track the movements ORGANIZERS: Michael G. Fried, According to the Wachowski broth- with specic ECM components and developments in understanding or accommodate noncanonical base of individual proteins involved in University of pairs. is ASBMB annual meet- replication, repair and recombination. ers’ “e Matrix” lm trilogy, a with each other. Emerging studies interactions between the ECM and Kentucky College matrix is a slick cyberspace that com- show that interactions between the growth factors as well as how cells ing symposium on DNA replication e third session will explore the of Medicine, and repair will provide a present-day range of DNA topologies present in and Myron F. Goodman, University of Southern puter hackers inhabit. For biochem- ECM and growth factors can be use proteases and kinases to modify overview of important parts of these repair complexes and the adaptations California ists, it is a far more dazzling structure tailored to achieve specic cellular the ECM during development and than that. responses. disease. In this ASBMB annual meeting symposium, experts on extracellular The good (development), Design your niche matrices will enlighten us about how the bad (disease) e nal session will present innova- PROTEIN NONFOLDING AS A REGULATORY PHENOMENON proteases and kinases control extracel- tive approaches being used to reveal lular matrix structure and function as and the matrix new mechanisms by which cells Challenging the central dogma well as how the extracellular matrix In the second session, new informa- generate and respond to the ECM regulates stem-cell niches, growth tion on the impact of mutations in niches during development and in By Elizabeth Rhoades and Scott Showalter factor and integrin function, and cell ECM components in human devel- disease. Investigations that incor- and tissue behavior in development opment and disease will be presented porate mechanical cues and the Biochemistry students learn that unfolded, proteins lack stable second- Given that as much as 40 percent and disease. along with studies on novel ECM 3-D microenvironment will receive protein folding is required for func- ary and tertiary structures under of the eukaryotic proteome is par- components that a ect development emphasis. tion. However, over the past 25 years, physiological conditions, and many tially or entirely disordered, the scope Secret liaisons and disease. a group of nonfolding proteins that remain disordered even upon binding of the problem and the need for new ORGANIZERS: Jeff between growth factors Gorski, University challenge the structure–function to their molecular partners. eir insights are enormous. is ASBMB Matrix makeovers: cells, of Missouri–Kan- paradigm have been identied and lack of stable structure and highly annual meeting symposium will high- and integrins exposed sas City School shown to be unexpectedly prevalent. dynamic nature make them challeng- light computational and experimental e rst session will examine how proteases and kinases of Dentistry, and Intrinsically disordered, or natively ing to study. advances in this research area. growth factors and integrins interact e third session will focus on recent Karen Lyons, University of California, Los Angeles

24 ASBMB TODAY SEPTEMBER 2014 SEPTEMBER 2014 ASBMB TODAY 25 Upcoming ASBMB NEW DIRECTIONS IN ENZYMOLOGY events and deadlines

Mechanistic enzymology SEPTEMBER Sept. 8–10: ASBMB Hill Day, Washington, D.C. Assistant Professor, and protein-structure function Chemistry Department, Full-Time, By Kate Carroll and Liz Hedstrom Sept. 23–24: ASBMB exhibits at the National Tenure-Track, Fall 2015 Institutes of Health Research Festival, Bethesda, Md. Salary: Depends on Qualifications It’s been almost 90 years since the Function detectives enzyme complexes and highlight isolation of urease, yet a vigorous examples of protein oligomerization Job Type: Faculty In any newly sequenced genome, OCTOBER debate continues about how enzymes as a regulatory strategy. Location: Main Campus, 1928 Saint Mary’s Road, Moraga, as many as 70 percent of the genes Oct. 2–6: impart such large rate enhancements Special symposium, Transcriptional CA 94556 do not have assigned functions. It is to slow reactions. is ASBMB My one and only Regulation: Chromatin and RNA Polymerase II, clear, then, that a substantial fraction Responsibilities: Teach courses in biochemistry as well as annual meeting symposium will Snowbird, Utah of biochemical space still remains to Of course, rate acceleration is only introductory courses in general chemistry and/or organic chemistry. examine modern issues in mechanis- part of what is amazing about enzyme Maintain a vibrant research program in some area of biochemistry be mapped. is session will spotlight Oct. 15: Fall application deadline for ASBMB tic enzymology and protein-structure recent successes in assigning functions catalysis. How enzymes discrimi- and supervise student research projects. Contribute to ongoing degree-accreditation modernization of curriculum and laboratory instrumentation. function. to orphan enzymes, the discovery of nate between substrates is far more complex than the simple lock-and- Participate in departmental and College activities including new activities and metabolites. Oct. 16–18: key model. is session will discuss ASBMB exhibits at the annual meeting committee work and grant-writing. Participate in core curriculum Co-opting cofactors of the Society for Advancement of Hispanics/ Collective power strategies for substrate recognition programs: January Term, Collegiate Seminar, and/or chemistry Recent investigations have revealed and reaction specicity. Chicanos and Native Americans in Science, courses for non-science majors. The candidate is also expected to that even a well-studied cofactor such Enzymes operate in a crowded milieu Los Angeles have a strong commitment to academic advising and mentoring a as NAD has some unexpected tricks ORGANIZERS: Kate diverse student population. that fosters macromolecular complex Carroll, The Scripps up its sleeve. is session will discuss formation and complicated qua- Research Institute, Experience and Qualifications: PhD in biochemistry (preferred) new developments in cofactor biosyn- ternary behavior. is session will and Liz Hedstrom, NOVEMBER or chemistry required. Primary consideration will be given to thesis, chemistry and dynamics. examine new tools for characterizing Brandeis University Nov. 6: Deadline for volunteered abstracts for the candidates with substantial experimental experience in biochemistry, 2015 ASBMB annual meeting in Boston though expertise in closely-related interdisciplinary fields may also be considered. Candidates should have evidence of scholarly Nov. 7: e ASBMB and Florida Biomedical Career achievement and a plan for future research that is suitable for undergraduate collaboration. Saint Mary’s is committed to PLENARY LECTURERS Symposium, Jupiter, Fla. assembling a diverse faculty. Talks to put on your itinerary Nov. 11: Deadline for travel-award applications for Supplemental Information: the 2015 ASBMB annual meeting in Boston Application Instructions: Please apply online at http://apptrkr.com/505084 C. David Allis, e Rockefeller University Nov. 11–15: ASBMB exhibits at the Annual Bio- Beyond the double helix: varying the terrain of epigenetic landscapes 1. lnclude a cover letter that specifically addresses how you meet medical Research Conference for Minority Students, in development and disease the qualifications of the position and are prepared to support the San Antonio, Texas mission of the College. Bonnie L. Bassler, Princeton University 2. Please submit a curriculum vitae, a statement of teaching Manipulating quorum sensing to control bacterial pathogenicity philosophy, a summary of research plans, and a copy of graduate DECEMBER transcripts. All documents should be uploaded as pdf or MS Ian A. Wilson, e Scripps Research Institute Dec. 1: Deadline for proposals for ASBMB 2016 Word files. Structural basis of broad neutralization of viral pathogens special symposia In addition, please arrange to have three current letters of recommendation sent to: December 7–9: ASBMB exhibits at the American Zhijian James Chen, University of Texas Southwestern Amy Bockman, administrative assistant Medical Center at Dallas Society for Cell Biology annual meeting Chemistry Search Committee Enemy within – immune and autoimmune responses to the cytosolic in Philadelphia, Booth 1004 e-mail: [email protected] DNA and RNA (Also ASBMB-MERCK award winner) postal service: Saint Mary’s College of California 1928 St. Mary’s Road Rachel Klevit, University of Washington PMB 4527 Structural, functional and mechanistic diversity in protein ubiquitination Moraga, CA 94575 (Also Fritz Lipmann Lectureship winner) DEADLINE: Review of aplications will begin September 24, 2014 but the position will remain open until filled. EOE

26 ASBMB TODAY SEPTEMBER 2014 SEPTEMBER 2014 ASBMB TODAY 27 FEATURE

“Punk rock, at its best, embraces an openness to experience, a s there something inherent to makes it so amenable to creative reliance on reason and evidence, punk rock that attracts scien- people? Punk is “thinking for yourself I tists? At rst blush, there would and doing what you want – and not and a questioning of received seem to be little overlap between the accepting something as truth just methodical deliberation of science because someone else says it,” explains wisdom. Science, which is based and the loud aggression of punk. Yet, Dexter Holland, the lead singer for on the naturalist perspective, is also upon deeper inspection, the similari- the O spring, who is working on his ties start to become apparent. Both Ph.D. at the University of Southern about questioning and not settling are magnets for individuals willing to California. He says that the “attitude for dogma.” question convention. Both involve of questioning things” appeals to a search for truth. And both rely on people who like to think deeply about – GREG GRAFFIN, “ANARCHY EVOLUTION” creative insights and breakthroughs issues. that spur passion and excitement. e proles of Aukerman, Holland “If I write a song, to me, it’s no dif- and Gran featured in this issue ferent than if I make some discovery explore how each musician-scientist in the lab,” says Milo Aukerman, a has used his creative energy to foment plant biochemist working at DuPont successful forays in the lab and on who also fronts the punk-rock band stage. Moreover, what they have to Descendents. “Your heart races, and say about the juxtaposition of their you have this sense of exhilaration.” scientic and musical careers goes a Bad Religion lead singer Greg long way toward erasing the stereo- Gran, who also is an evolutionary types of the geeky, introverted, lab biology lecturer at Cornell University, coat-clad scientist and the angry, agrees: “I think there’s a tremendous impulsive, Mohawk-sporting punk. similarity in creativity in science and Holland captures it best when he in music or art.” says, “Something that is established So what is it about punk that doesn’t necessarily mean it’s true.”

28 ASBMB TODAY SEPTEMBER 2014 SEPTEMBER 2014 ASBMB TODAY 29 A champion of the nerds Milo Aukerman is a molecular biologist as well as ative energy and focus on music for a ambition of climbing the corporate while,” he says. “en maybe a couple ladder. “I just want to have a really the lead singer of the punk-rock band Descendents of months later, the science takes the fascinating problem to work on,” he driver’s seat, and that ends up being says. Immersed in research for now, By Georey Hunt and Rajendrani Mukhopadhyay where my creative energies go.” Aukerman sees the band as “a hobby Aukerman’s scientic career has that allows me to maintain (a) youth- challenged his own ideas about stereo- ful outlook on life and a freshness in I want to be stereotyped / Growing up in Los Angeles, types within the research enterprise. life.” Aukerman had punk rock right on his After going along the traditional sci- Despite the unconventional shift- I want to be classied. doorstep. “In the late ’70s and early entic academic path, including two ing that he does between the worlds – DESCENDENTS, “SUBURBAN HOME” ’80s, LA punk rock was just blos- postdoctoral fellowships, Aukerman of molecular biology and punk rock, soming,” he says, listing Black Flag, had his heart set on a faculty posi- Aukerman says he’s never su ered hatever inspired Milo Auker- the Germs, X and the Minutemen as tion at an academic institution. By “any kind of fallout.” Fellow scien- man to write those lyrics, his musical inspirations back then. the time he followed his wife, Robin tists, he says, “are very interested “It was a pretty amazing time just to Andreason, to Delaware, where she in someone who’s not just stuck at From left: Milo Aukerman (IMAGE COURTESY OF AUKERMAN). W he has spent the past three Descendents band members Milo Aukerman and decades doing everything not to live be involved in that (scene) and play was about to take up a faculty position the lab bench all day and who can Stephen Egerton (IMAGE COURTESY OF CHAPMAN BAEHLER). at the university’s department of phi- actually go out and do something Descendents’ logo and “Cool To Be You” album cover up to them. As both the lead singer on the same shows as some of these (IMAGES COURTESY OF FAT WRECK CHORDS). Milo Aukerman in of the seminal Los Angeles pop-punk bands.” losophy, “I was really on the academic completely di erent, something a greenhouse (IMAGE COURTESY OF AUKERMAN). Descendents track,” he says. But friends who were wacky and bizarre.” Likewise, for members, from left, Karl Alvarez, Stephen Egerton, band Descendents and a plant molec- Torn between his dual loves of Milo Aukerman and Bill Stevenson (IMAGE COURTESY OF ular biologist at DuPont, Aukerman music and science, Aukerman crafted already working at DuPont suggested peers in punk rock, “even if they don’t TONY NELSON). The band’s “’merican” abum cover (IMAGE COURTESY OF FAT WRECK CHORDS). has followed a decidedly nontradi- the perfect compromise, now immor- that he consider applying there. really understand what I do neces- tional career path, one that allows him talized in the title of the band’s debut He accepted a job at DuPont as sarily, it’s so di erent to them that it to embrace the most dynamic qualities album, “Milo Goes to College,” which a principal investigator and admits becomes more of a facet that can be of his two passions. Both a scientist was released in 1982. Inspired by his thinking, “Oh, great. Here we go, into fascinating,” he says. Even Aukerman’s and a musician, Aukerman blurs the actual departure from the band to corporate research.” However, Auker- parents have come around to support- lines between conventional denitions study biochemistry at the University man discovered that the research envi- ing his career decisions. “Whenever I of these two professions. of California, San Diego, the album ronment at DuPont is very much like hang out with my mom, she’s trying As a high- cover featured a caricature of Auker- the one he was used to in academia to introduce me as ‘my rockstar son,’” school student man, complete with a white button- “but in a corporate setting, without he says with a laugh. fascinated by the down shirt, black tie, thick-rimmed all the headaches of grant writing and You might think that Aukerman is discovery of the glasses and buzz cut, cementing the teaching and all that kind of stu .” unique in his ability to rise above clas- structure of DNA band’s iconic nerd image. “Punk “In fact, the rst few years were sications and challenge the assump- and the recom- provided me that avenue to be di er- an amazing time for me,” he says. tion that a scientist or a punk has AUKERMAN binant DNA ent,” says Aukerman, who earned his During his time at DuPont, Auker- to look or act a certain way. But he experiments of Stanley Cohen, Paul bachelor’s degree in biology in 1986. man and his colleagues have made doesn’t think so. “ere’s a stereotype Berg and Herbert Boyer, Aukerman For the next several years, Auker- several important discoveries, includ- of a punk being this tough, tattoo- deed the science-geek stereotype man bounced between touring and ing uncovering that microRNAs are laden meathead,” says Aukerman. by joining up with Tony Lombardo, recording with the band and working involved in controlling owering time. “But in fact, many nerds ended up Frank Navetta and Bill Stevenson at UCSD to get his Ph.D. in bio- ese days, as part of the DuPont turning to punk, because it was a way in Descendents in 1980 to make a chemistry. e two lifestyles might Crop Genetics group, Aukerman of releasing some of that frustration splash in the punk-rock scene. “My seem to be conicting, but Aukerman is studying the model organism that they had for being nerds.” parents denitely had an expectation sees them as complementary. “Some- Arabidopsis thaliana to understand Having spent a lifetime avoiding that I would be an academic-type times when the science is getting (to the genetic players for traits such being stereotyped or classied, Auker- person,” recalls Aukerman. However, be) a little more of a drudge, that’s as drought tolerance and nitrogen man does defy the way labels are “I needed a place to get my ya-ya’s when I just turn to music and gure, assimilation that will aid engineering applied. As he proudly puts it, “Punks out and actually be di erent.” well, now I’m going to take my cre- hardier strains of maize. He has no are the champions of the nerds.”

30 ASBMB TODAY SEPTEMBER 2014 SEPTEMBER 2014 ASBMB TODAY 31 Keep ’em separated Dexter Holland, the lead singer of the punk-rock band e O spring, has a lot of di erent interests. One of them is biology. By Rajendrani Mukhopadhyay and Georey Hunt

efore he became famous as the Finding inspiration from di erent lead singer for the punk-rock areas is integral to Holland’s psyche. B band e O spring in the As a singer, a licensed pilot, and a mid-1990s, Dexter Holland was just certied hot-sauce maker, Holland another graduate student toiling away is continually nding new creative in a laboratory at the University of outlets for his seemingly boundless Southern California. One day, he energy. “I like making things hap- pulled two ve-liter Erlenmeyer asks pen,” he explains. “I like to do a lot full of steaming hot LB broth out of of stu .” Next up on his list: to nish band?” Holland remembers them bandmates around North America IMAGE COURTESY OF THE OFFSPRING the autoclave and put them in the that Ph.D. in virology he started two saying. “I think they secretly hoped it and Europe. The Offspring band members, from left Greg Kriesel, Dexter Holland, Kevin “Noodles” Wasserman and safety hood to cool down. But the decades ago. “It’s been a long road,” was a phase.” e band’s long-lasting success Pete Parada cooling process was taking forever. admits Holland. In a way, they were right. After 20 has a orded Holland the freedom “ey were right next to each other,” A native of southern California, years of touring and recording with to indulge his passions and explore a remembers Holland. “I thought, Holland formed e O spring with e O spring, Holland’s focus has variety of distinct pursuits. Hot sauce ‘ese things are never going to cool Greg Kriesel, Ron Welty and Kevin nally come back to his Ph.D. “If I is a case in point. As someone hailing o . I’ve got to keep ’em separated.’” “Noodles” Wasserman in high school. don’t do it now,” Holland says, “I’m from southern California, Holland is e phrase As the band struggled to make it big not going to do it 10 years from now.” well acquainted with what makes a struck Holland. in the early 1990s, Holland started a Working with Suraya Rasheed at good hot sauce and wanted to cook “I thought that Ph.D. at USC and got as far as pass- USC, Holland is studying the roles of up his own. “I thought it would be was a funny line,” ing his oral qualifying exams. But in microRNA sequences in inuencing cool, because it sounds funny and he recalls of what 1994, e O spring’s third album, the infectivity of the human immuno- sounds fun,” he says. Holland spent would become the “Smash,” exploded onto the charts, deciency virus. “I’m not predicting two years crafting his sauce, admitting HOLLAND signature hook for soaring to No. 4 on the U.S. Bill- necessarily making (science) a career,” that he took “a little bit of a scientic the band’s breakthrough hit, “Come board 200 and catapulting the band says Holland. “But I did want to n- approach” in perfecting the recipe. Out and Play.” “It was literally a biol- into superstardom. ish something that I started.” Gringo Bandito Hot Sauce is now ogy inspiration.” At that point, it was clear to Hol- ankfully for Holland, his music available for sale in grocery stores in land what he needed to do – he had career is going pretty well. “Smash” various states and online. to put his academic pursuits on hold. has sold more than 6 million cop- It’s anybody’s guess what Holland Others were not as sure. One of his ies in the U.S. and more than 12 might do next. He already devotes thesis advisers, completely befuddled million copies globally, qualifying it some of his time to the Innocence as to why Holland wanted to take as the best-selling independent-label Project, an organization that works a leave of absence from graduate album to date. More platinum-selling to exonerate wrongfully convicted school, suggested Holland take time albums have followed, establishing prisoners through DNA testing. In out from the band instead. “is is e O spring as one of the most this regard, having a Ph.D. at the end when we were on MTV!” says an successful bands in music history. of his name adds “a legitimacy” that incredulous Holland. His parents “I’ve been very fortunate to be able to could help people listen to what he were equally confounded. “You have pluck an electric guitar for a living,” has to say about his favorite charity. Clockwise from top: Dexter Holland helps ready Gringo Bandito hot sauce (IMAGES COURTESY OF CHAPMAN BAEHLER). A this great opportunity of getting a acknowledges Holland. e band After that? “Maybe Bono will give me bottle of Gringo Bandito hot sauce. Band logo for The Offspring (IMAGE COURTESY OF THE OFFSPRING). The Offspring’s “Smash” album cover (IMAGE COURTESY OF EPITAPH RECORDS). Dexter Holland stands with his prop plane (IMAGE COURTESY grad degree, and you’re throwing continues to be active, and Holland a call, and I can help him ght AIDS OF CHAPMAN BAEHLER). it away to go play in a punk rock spent this summer touring with his in Africa,” he jokes.

32 ASBMB TODAY SEPTEMBER 2014 SEPTEMBER 2014 ASBMB TODAY 33 ing popularity resulted in an ever- similar approach to songwriting, one expanding audience becoming aware that is based primarily on storytelling. Against the grain of the sophisticated brand of intellec- “How you approach a subject like tualism that the band was promoting. extinction or the fossil record, there’s Whether he’s fronting the punk-rock band Gran says Bad Religion’s mantra has really a story to be told there,” Gran been to “liberate the closed-minded- says. Similarly, the “songs that I’ve Bad Religion or delivering a lecture ness of punk rock” by rejecting the written are stories in themselves.” vacant anarchism and brutal nihilism e nature of those songs is what on evolution, Greg Gran is constantly often associated with the genre. “Part sets Gran and his band apart. challenging his audiences to question convention of the beauty of punk tradition is not Johnny Ramone supposedly once giving into stereotypes,” he says. described e Ramones’ songs as By Georey Hunt and Rajendrani Mukhopadhyay Jumping back into academics as a being “fairly long songs played very, full-time lecturer at UCLA in 2007 very quickly.” In much the same vein, was therefore a relatively smooth tran- listening to Bad Religion songs is like sition for Gran. “I think there’s a listening to a lecture given very, very “Early man walked away as f you’re hoping to get a punk-rock things came together [at] that time quickly. “We are One People, performance in his evolution- in my life,” he remembers. Inspired tremendous similarity in creativity in modern man took control / science and in music,” he says. e wide-ranging subject matter I ary biology class, Greg Gran is by the poetic lyricism of punk rock and extensive vocabulary in Bad Reli- and we can all strive for As an instructor, Gran readily eir minds weren’t all the quick to dash your hopes. “You can’t peers like e Germs as well as the gion lyrics demand concentration, one aim: the peaceful slam dance when you’re listening to intellectual freedom he found in the admits that “my reputation precedes same, to conquer was his me sometimes,” leading to potential attentiveness and even research, some- me lecture,” says the Cornell Univer- theory of evolution, Gran teamed thing that Gran says is consciously and equitable survival of goal / So he built his great sity lecturer and lead singer for the up with fellow mists Jay Bentley, confusion and disappointment for his students who sign up for his class in part of his songwriting and lectur- humanity. To have arrived empire, and he slaughtered legendary punk band Bad Religion. Brett Gurewitz and Jay Ziskrout to ing processes. “Certainly one of my For more form Bad Religion, a punk band that hopes of seeing an exhilarating punk- on this earth as the product his own kind / en he died a rock performance. “It’s nowhere near interests in songwriting is to challenge than thirty years, has deliberately deed and o ended people to think,” he states. “Similar to of a biological accident, Gran has been convention but in a decidedly philo- as exciting,” says Gran. “I’m not a confused man, killed himself loud, boisterous lecturer.” my goals in lecture.” studying, research- sophical way. “My personal discovery Gran uses his songs to inspire his only to depart it through with his own mind / We’re Yet keeping his audience members ing and teaching of evolution and starting a punk band audience to question and analyze the on their toes is something Gran arrogance, would be the only gonna die from our own evolutionary called Bad Religion – they were nicely validity of conventional institutions. GRAFFIN excels at. “I know people look at me biology while harmonious,” states Gran. Topics drawing Gran’s discern- ultimate irony.” arrogance.” as some kind of schizophrenic person simultaneously fronting one of the One of the rst songs Gran wrote ing ire include pop culture, religion, who’s doing these two things but not – CHARLES DARWIN, ON THE – BAD RELIGION most inuential bands to come out for Bad Religion, titled “We’re Only government, and even science and focusing on any one,” claims Gran. ORIGIN OF SPECIES of the hardcore punk scene. Moving Gonna Die,” was directly inspired by technology. But as he sees it, the process of con- back and forth between these two the nal sentences of Charles Dar- Targeting science may seem to identities, Gran seeks to inspire his win’s “Origin of Species.” Since then, structing and then delivering a lecture audiences to question orthodoxy and his interests in music and science on evolutionary biology relies on a CONTINUED ON PAGE 36 search for truth, whether in a lecture have continued to grow in parallel. hall or in a music club. “ey became the two threads of my Gran’s dual lifestyles trace back life,” says Gran, who rst began to his high-school days in the late his instructional duties in 1987 as a 1970s in California’s San Fernando graduate teaching assistant for a com- Valley. A Midwestern transplant with parative anatomy course at University a fondness for progressive rock bands of California, Los Angeles, around like Utopia and King Crimson, Graf- the same time Bad Religion began to n became fascinated by evolution in achieve a degree of prominence within his biology class. “My parents never the punk-rock community. raised me with any religion,” he says. As the band’s fortunes continued Evolution “gave me a mythology of to improve, science got temporar- where I came from that wasn’t based ily pushed to the side, with Gran on any stories in the Bible.” putting his academic pursuits on His decidedly unpopular interests hiatus for several years before nally drew him to punk rock, which at obtaining his Ph.D. in zoology from that time was a refuge for all types Cornell in 2003. From left: Bad Religion “Crossbuster” logo (IMAGE COURTESY OF EPITAPH RECORDS). Bad Religion performing live (IMAGE COURTESY OF ROBERT GASPARRO). Bad Religion’s “Suffer,” of outcasts. “ese unpredictable In the interim, Bad Religion’s grow- “Against the Grain” and “True North” album covers (IMAGES COURTESY OF EPITAPH RECORDS).

34 ASBMB TODAY SEPTEMBER 2014 SEPTEMBER 2014 ASBMB TODAY 35 ANNUAL REVIEWS It’s about time. Your time. It’s time well spent.

Annual Review of Microbiology micro.annualreviews.org • Volume 68 • September 2014

Editor: Susan Gottesman, Bethesda, MD

The Annual Review of Microbiology, in publication since 1947, covers significant developments in the field of Microbiology, encompassing bacteria, archaea, viruses, and unicellular eukaryotes.

TABLE OF CONTENTS: • Beyond My Wildest Expectations, Eugene Nester • Altered Egos: Antiobiotic Effects on Food Animal Microbiomes, • Viral Miniproteins, Daniel DiMaio Heather K. Allen, Thad B. Stanton • Salmonella enterica Serovar Typhi and the Pathogenesis of IMAGE COURTESY OF MYRIAM SANTOS matters to Gran, ultimately, • 6S RNA, A Global Regulator of Transcription in Escherichia coli, CONTINUED FROM PAGE 35 Typhoid Fever, Gordon Dougan, Stephen Baker Bad Religion band members, from left, Brian Baker, is the impact his work is having on Bacillus subtilis, and Beyond, Amy T. Cavanagh, Greg Hetson, Brett Gurewitz, Greg Graffin, Jay conict with Gran’s proclamation his audience. For Gran, “the aston- Karen M. Wassarman • Friend Turned Foe: Evolution of Enterococcal Virulence and Bentley, Brooks Wackerman to be a naturalist, but he sees it as a ishing phenomena that come from • Taming Wild Yeast: Potential of Conventional and Nonconventional Antibiotic Resistance, Daria Van Tyne, Michael S. Gilmore healthy part of the scientic process. the connection you can make with an Yeasts in Industrial Fermentations, Jan Steensels, • Bacterial Sigma Factors: A Historical, Structural, and Genomic “You can’t just have blind faith in audience member is something that I Kevin J. Verstrepen Perspective, Andrey Feklístov, Brian D. Sharon, Seth A. Darst, something,” he cautions. “You need want to tap into and try and nd.” • Lipoteichoic Acid Synthesis and Function in Gram-Positive Carol A. Gross to temper it with evidence.” Sticking Gran says he strives to improve Bacteria, Matthew G. Percy, Angelika Gründling • Fungal Membrane Organization: The Eisosome Concept, with his nonconformist approach, his own performances. “I’ve written • Temperature Sensing by Membranes, Diego de Mendoza Lois M. Douglas, James B. Konopka Gran even prefers Charles Darwin’s something like 300 songs in my life,” • What Ecologists Can Tell Virologists, John J. Dennehy • Viroids: Survivors from the RNA World? Ricardo Flores, Selma Gago-Zachert, Pedro Serra, Rafael Sanjuán, “Voyage of the Beagle” to the canoni- he says. “I think I’ve gotten bet- • The Medium Is the Message: Interspecies and Interkingdom Santiago F. Elena cal “Origin of Species,” which he ter and better as I’ve done more of Signaling by Peptidoglycan and Related Bacterial Glycans, considers “pretty dry reading.” them.” Likewise, Gran continues Jonathan Dworkin • Bacterial Type III Secretion Systems: Specialized Nanomachines for Protein Delivery into Target Cells, Jorge E. Galán, Currently, Gran co-teaches an to improve his teaching skills. “My • Prokaryotic Ubiquitin-Like Protein Modification, Maria Lara-Tejero, Thomas C. Marlovits, Samuel Wagner introductory course on evolution [class] reviews have all been good,” Julie A. Maupin-Furlow • Subterfuge and Sabotage: Evasion of Host Innate Defenses by at Cornell during the fall semester, he says, but “I’m trying to get more • The Importance of Microbes in Animal Development: Lessons Invasive Gram-Positive Bacterial Pathogens, Cheryl Y.M. Okumura, leaving him plenty of time, as he experienced at lecturing.” from the Squid-Vibrio Symbiosis, Margaret J. McFall-Ngai puts it, to “take care of band busi- Victor Nizet Here, nally, Gran notes a small • The Tiniest Tiny Genomes, Nancy A. Moran, Gordon M. Bennett ness.” Gran acknowledges that his disconnect between his two passions. • Fluorescence Imaging for Bacterial Cell Biology: From Localization • Effect of Antibiotics on Human Microbiota and Subsequent musical forays outstrip his e orts in “I’m not going to clubs every night, to Dynamics, From Ensembles to Single Molecules, Zhizhong Yao, Disease, Kristie M. Keeney, Sophie Yurist-Doutsch, because I’m preparing for lecture,” he Rut Carballido-López the classroom, at least for now. “I’ve Marie Claire Arrieta, B. Brett Finlay performed far more concerts than I says. ough it may be blasphemy to • Cellular Sensing of Viral DNA and Viral Evasion Mechanisms, • Recombination Promoted by DNA Viruses: Phage λ to Herpes have given lectures,” he says. his punk-rock peers, this is a state- Megan H. Orzalli, David M. Knipe Simplex Virus, Sandra K. Weller, James A. Sawitzke While he looks forward to con- ment with which most professors can • Regulation of Virulence of Entamoeba histolytica, Chelsea Marie, tinuing with both his passions, what empathize. • The Peculiarities and Paradoxes of Plasmodium Heme Metabolism, William A. Petri, Jr. Paul A. Sigala, Daniel E. Goldberg

1 3 6 8 9 10 • Biomass Utilization by Gut Microbiomes, Bryan A. White, IMAGES COURTESY OF: 1. EPITAPH RECORDS, 2. 4 7 24 2 ROBERT GASPARRO, 3. CHAPMAN BAEHLER, 4. Raphael Lamed, Edward A. Bayer, Harry J. Flint 11 FAT WRECK CHORDS, 5. CHAPMAN BAEHLER, 6. Geoffrey Hunt (ghunt@asbmb. ROBERT GASPARRO, 7. CHAPMAN BAEHLER, 8. org) is the ASBMB’s public out- 5 EPITAPH RECORDS, 9. TONY NELSON, 10. CHAPMAN 12 BAEHLER, 11. EPITAPH RECORDS, 12. ROBERT reach coordinator. Follow him on 23 GASPARRO, 13. CHAPMAN BAEHLER, 14. FAT Also available from Annual Reviews: Twitter at www.twitter.com/ 22 WRECK CHORDS, 15. THE OFFSPRING, 16. KATIE thegeoffhunt. Rajendrani HOVLAND, 17. EPITAPH RECORDS, 18. EPITAPH RECORDS, 19. ROBERT GASPARRO, 20. MYRIAM NEW! • Annual Review of Virology Mukhopadhyay (rmukhopadhyay@ 13 14 asbmb.org) is the senior science 20 SANTOS, 21. MILO AUKERMAN, 22. EPITAPH RECORDS, 23. CHAPMAN BAEHLER, 24. EPITAPH Access these and all Annual Reviews journals via your institution at www.annualreviews.org writer and blogger for ASBMB. 21 19 RECORDS 15 Follow her on Twitter at www. 17 16 twitter.com/rajmukhop. 18 ANNUAL REVIEWS: Connect With Our Experts Tel: 800.523.8635 (US/CAN) | Tel: 650.493.4400 | Fax: 650.424.0910 | Email: [email protected] 36 ASBMB TODAY SEPTEMBER 2014 SEPTEMBER 2014 ASBMB TODAY 37 Most people who will criticize opportunities beyond your campus. friends’ lives progressed into promo- you are going to do it from a place For example, if you decide during tions, marriages and other accom- of well-meaning — with the goal your graduate studies that you’d like plishments and milestones. of helping you and your work to to teach but your school o ers few Just because you’re in graduate progress in the right direction. Always ways to gain teaching experience, school doesn’t mean the rest of your be open to considering what those contact nearby schools. In short, no life has to stop. In fact, it’s the other people have to say. matter what your reason for choosing parts of your life that often will save to enter graduate school, continue to your sanity when lab life is giving you Explore all career options explore all of your interests. trouble. So go on dates, go to hockey games (go Bruins!), have karaoke ough you may enter graduate nights — do whatever it is you have school with a clear plan of what career Live your life to do to stay connected to the outside lies ahead for you, be open to that Finally, I urge you to remember to world. plan changing a little or a lot. It is not have a life outside of the lab. Becom- In closing, graduate school is your uncommon for people to enter gradu- ing engrossed in your project is opportunity to hone your skills as you ate school with the goal of becoming important (own it!), but you don’t transition from a classroom student an academic researcher or executive of want to live in a vacuum and cut o to an independent researcher. is a biotech company and realize half- all social down time. Open letter to the incoming time marks the start of you shaping way through that those career paths Breaks are important for allowing your unique career path, and it is a are not right for them after all. your brain to rest. Often, time away time of immense professional and at is OK, and that’s why it’s from the lab brings you out of the cohort of graduate students personal growth. good to explore as many career tunnel for long enough that when options as possible while you are still you return to work you spot issues Learn as much as you can, and enjoy By Kelly Hallstrom a student. Do your homework, and you otherwise wouldn’t have noticed. the ride! nd out what career-development Aside from giving you and your Kelly opportunities your school provides brain a break, having outside interests As a graduate student, however, embrace fully this new responsibility. and take advantage of them. On ensures that your life in general Dear newbie graduate students, Kelly Hallstrom you transition from being a helper to Don’t be afraid of it, though. Instead, the ip side, don’t feel limited by doesn’t stop just because you’re in ([email protected]) o all of you about to start on having ownership over an entire proj- learn from it. Become the expert. the opportunities for growth avail- graduate school. I know people who is a Ph.D. candidate at the the exciting, confusing, roll- ect. is situation was new to me. I Own your project. able at your school. You may have to have lamented over “wasting their University of Massachusetts Medical School. T ercoaster-of-emotions path of inherited my project from a postdoc, seek out volunteering or networking youth” in graduate school while their graduate school, I’d like to share some and it took some time for me to stop Swallow your pride advice and lessons I’ve learned (and thinking about my work in terms You’ve been warned: You are going to am still learning!) during my own of what I needed to do to nish this be criticized. A lot. Last call for open letters! Read the series online experience as a graduate student in project he started and start thinking When you give presentations biological sciences. everything from that point forward Dear readers, Rajendrani Mukhopadhyay, “An open letter to a professor was my project. at department seminars or at con- who once comforted me” (December) If you’ve enjoyed our “Open Letters” series and is ownership is exciting. Your ferences or meet with your thesis Own your project have contemplated contributing a piece to it, Michael Mira, “A belated love letter to my rst-grade science ideas, perhaps for the rst time in committee, your approaches and the time has come! We will accept open letters teacher” (January) Graduate school is going to be vastly your research experience, are given conclusions are going to be targets for through Sept. 30. After that, we’ll be gearing up di erent from your undergraduate weight and consideration. You are questioning and criticism. But this is Akshat Sharma, “An open letter from a not-so-good Brahmin for our 2015 series (described on the inside of experiences. As an undergrad, you involved in the decisions of which part of science. Science is constantly boy” (February) the cover of this issue). Send your submission to most likely helped out on another experiments to do and which to self-checking and self-correcting. at [email protected]. Paul Sirajuddin, “An open letter to my younger self” (March) person’s project, running a few PCRs shelve perhaps for later. can’t happen without criticism. Also, I’d like to express how grateful I am to here, taking population samples is responsibility also can be As much as you may think you’re Harvey J. Armbrecht, “ ank God for overlapping genes” there. You were a helper of sorts, daunting at times. You are in charge doing everything right, it’s easy to those contributors who have brought the “Open (April) Letters” series to life. On behalf of our readers, learning a little of this and that as you of understanding the how and why of develop tunnel vision and to forget Philip Yeagle, “On hindsight and gratitude” (May) went along. It was a great opportu- every step, technique and experiment. to approach your work from di erent thank you for your courage, humor and sincerity. Bill Sullivan, “ e road to professor” (June/July) nity to get your feet wet in research. You are expected to know the state of perspectives. is may cause you to Best, If you worked in a lab after your the art of the eld surrounding your miss an alternative explanation or key Angela Hopp Angela Hopp, “An open letter to press ocers who won’t undergraduate studies, you prob- project, to remain up to date on new experiment. Without those people in Editor, ASBMB Today promote unembargoed research papers” (August) ably had more responsibilities but relevant ndings and to contribute the crowd to point out your errors, most likely were still an assistant to new ideas. your work (and the science behind it) someone else. It might take a little time to can’t improve.

38 ASBMB TODAY SEPTEMBER 2014 SEPTEMBER 2014 ASBMB TODAY 39 EDUCATION

students to explore multiple career quality and provide student salary pushing the employment bottleneck options during training may actu- support linked to R01s. An example down the road. A response to the NIH ally extend the training period but of this strategy, which we endorse, is A better option is to expand to good e ect. us, we propose the the recent plan for all NIH institutes opportunities for postdoctoral focus should move from minimizing to o er F-series grants. trainees who may not want faculty time to graduation to minimizing positions but aspire to be long-term Biomedical Research Workforce time to career. Postdoctoral training sta scientists. Sta scientist positions We also support tracking graduates allow these individuals to pursue We oppose increasing the number research careers within other labs to understand how they are moving of postdoctoral fellows supported Working Group Report into the job market, provided that through training grants. Postdoctoral without the responsibility of garner- this does not increase investigator salary support, linked to R01 grants, ing their own funding. eir experi- Biochemistry department leaders o er praise, criticism and recommendations administrative burden or increase is a historically e ective mechanism ence typically enhances the overall institutional administrative costs. that easily and eciently accommo- competence of laboratory sta . For By Bruce J. Nicholson and Richard L. Eckert We view as awed the recom- dates productivity and achievement. this sta scientist position to be a mendation in the Tilghman report, We support increasing the number viable career path, the NIH and reiterated in the recent PNAS of fellowships given to postdocs and academic institutions would have to editorial, that the fraction of stu- making them available to foreign accept and put in place a promotion- iomedical research in the NIH return to a focus on funding lower than the 7.5 percent national dents supported by training grants and-salary structure that endorses and United States is in crisis as basic science, other opinions in the average at that time (1). However, trainees. We also agree with the Til- be increased to enhance the quality ghman report authors that postdoc- supports these positions analogous to B the international leadership report have not been universally there is a shift within this segment, of training and shorten the time to what exists for research-track faculty. toral stipends should be increased, the nation has enjoyed for decades embraced. with employment opportunities in degree. Our own ad hoc survey of 26 academic research decreasing steadily but those increases should be linked is eroding in the face of economic Some of the recommendations universities revealed no di erences Faculty support while opportunities in industrial and to a concomitant increase in modular austerity and competition from other in the Tilghman report already have in time to degree when comparing countries that have made research a government research, administration, R01 budgets. e Tilghman report described a been implemented by the NIH. As students supported on training grants higher priority. is crisis has arisen teaching, scientic writing, advocacy In the recent PNAS perspective proliferation of what are known as we stand poised for implementation with those supported on individual as universities and research institutes, and other areas that demand people it is noted that increasing stipends soft-money positions at academic of additional steps that could a ect RO1 grants (see table). e enhanced which have based strategic plans on trained to think in an analytical without increasing grant support institutions. e reduced job security graduate and postgraduate training performance of students supported by assumptions of continued growth, and research for decades, the Asso- manner are increasing. us, we will reduce the number of postdocs, associated with these positions has training grants, cited in the Tilghman which was presented as a positive out- are faced with the reality of shrinking ciation of Medical and Graduate disagree with strategies that seek to created a negative image for research report, is likely the result of institu- come, but we question if this should federal research budgets and sharp Departments of Biochemistry con- reduce this pool of highly educated science as a career. As a response, the tional selection policies that place the be our goal, given the employment reductions in state funding for higher vened a working group to consider and in-demand individuals. We do, report recommended limiting the best students on training grants rather opportunities that exist for this group education. ese pressures demand the repercussions of the Tilghman however, enthusiastically endorse the percentage of faculty salary paid for than an inherent di erence in the described above! We propose, instead, a critical self-analysis as to how we report from the perspective of depart- idea of expanding training opportuni- by the NIH. quality of training. limiting the time that postdocs can can preserve the vibrant and creative ment chairs who work at the interface ties beyond the traditional academic AMGDB members are in a unique We are concerned that training be supported, which can be achieved U.S. scientic environment while also between faculty and institutional track. However, this comes with a position to understand the impact grants have been concentrated dispro- through enhancing career training devising new strategies for training administration. While we concur specic proviso. of soft money on investigators and portionately in elite institutions and and developing additional academic the next generation of scientists for a with some of the recommendations in We must not dilute the fundamen- institutions under pressure to reduce that this concentration will increase. career options. job market o ering fewer opportuni- the Tilghman report, we have serious tal goal of graduate training, which is hard-money budgets. We feel that Graduate education must serve a range We also support enhanced tracking ties in academia. reservations about others. to develop outstanding research scien- limiting faculty salary coverage on A National Institutes of Health tists who think independently and of academic institutions with broad of the career outcomes for postdoc- grants should not be achieved by geographical distribution to empower advisory committee headed by Shirley Graduate education analytically, as this is precisely what toral fellows so long as it doesn’t reducing the salary cap, as this will Tilghman made several recommenda- is valued by employers, academic or the broadest base of talent. We argue overburden principal investigators or reinforce the image that an academic tions addressing these issues in the A primary premise in the Tilghman otherwise. Moreover, training highly that this can be achieved best and increase institutional administrative research career is low paid and unsta- NIH Biomedical Research Workforce report and recent PNAS editorial is competent researchers is essential most eciently by linking student sal- costs. ble. Instead, we favor establishing Working Group Report published in that too many biomedical Ph.D.s are if the U.S. is going to maintain its ary support to individual R01s. We have signicant concerns about limits for principal investigator e ort June 2012 (1). Bruce Alberts, Marc being issued in light of the number international leadership role in the Having all students on training the recommendation in the Tilghman on individual grants (e.g., 25 percent W. Kirschner, Shirley Tilghman and of jobs available. However, this is biomedical sciences. For this reason, grants carries the additional cost of report to increase K-type transition for RO1s, 15 percent for R21s and so Harold Varmus recently revisited the true if one focuses only on traditional we disagree with the Tilghman report additional administrative burden awards designed to accelerate move- forth). report in a “Perspective” article in the academic careers. recommendation that we reduce the on investigators and institutions. ment of postdoctoral trainees toward In addition, limiting the number Proceedings of the National Academy Between 2002 and 2008, despite time it takes to earn a Ph.D. us, rather than expanding training independent positions. e problem of NIH grants that a single investiga- of Sciences (2). While researchers a 50 percent increase in biomedi- Instead, we recommend that the grants, we propose expanding Ruth L. is that it must be done in conjunction tor can hold, which the NIH has con- support some viewpoints expressed cal Ph.D. holders, unemployment emphasis be placed on shortening Kirschstein National Research Service with increases in R21 and R01 sup- templated, also will help. Implemen- in both of these documents, particu- remained constant at 2 percent for how long it takes for a graduate to Award fellowships, as those awards port available to investigators. Other- larly the recommendation that the that segment of the workforce, much enter the job market. Permitting encourage student initiative and wise, increasing K awards amounts to CONTINUED ON PAGE 42

40 ASBMB TODAY SEPTEMBER 2014 SEPTEMBER 2014 ASBMB TODAY 41 PROFESSIONAL DEVELOPMENT

CONTINUED FROM PAGE 41 TOP 30 INSTITUTIONS: tation of such a limit must coincide with the recognition by institutions Graduate Student T32 Positions Versus Time to Degree Passive obstructionism

and the NIH that many functions 2 1 Median Years 3 of faculty members — including Institution TG Slots to Degree NIH Rank By Andrew D. Hollenbach teaching, committee and professional Johns Hopkins 327 5.5 2 service, exploratory research, and Washington 278 6.13 5 writing of grant applications in new Wisconsin-Madison 261 5.73 21 really don’t have a lot of pet research areas — should be supported Michigan 259 5.9 6 peeves. OK, maybe that’s a lie; by the institution. Penn 258 5.7 3 I but most of the ones I have are Given the impact these changes UC-San Diego 231 6 8 the common ones. You know, people will have on our medical schools Yale 213 5.5 10 who don’t use their turn signals, peo- UCLA 209 6 11 and research universities, a movement ple who chew with their mouths open of faculty salaries from grants to UNC-Chapel Hill 197 5.5 13 UCSF 196 6.29 4 and something specic to the New institutional budgets needs to be Orleans region, people who say, “ax” phased in gradually. e NIH may Stanford 186 6 14 Univ. Chicago 174 5.88 27 instead of “ask.” However, my big- consider incentivizing this transition Harvard + MGH 164 6 1 gest pet peeve when it comes to my by directly linking institutional indi- Cornell 163 6 28 job is the people who say something rect-cost recovery levels to the progress UC-Berkeley 160 5.6 53 is impossible before even thinking institutions have made in covering Wash U 158 5.74 9 about how to make it possible. higher portions of faculty salaries. Minnesota 142 5.3 20 You know people like this: the In their PNAS commentary, Columbia 134 6.5 18 person who, when you talk to him Alberts and colleagues called for open Duke 131 5.45 12 or her about an experiment, tells you discourse. We hope this editorial con- Vanderbilt 130 5.75 16 all of the reasons why the experiment Pittsburgh 123 5.2 7 tributes a useful perspective to this won’t work instead of simply doing conversation and motivates the NIH Northwestern 121 5.7 29 Case Western 117 5.74 39 the experiment; the person who, what I like to call passive obstruction- because someone doesn’t want to to reconsider some of its actions. when you discuss a large-scale experi- ism; people aren’t actively saying that relinquish power. Regardless of how American science has made great Emory 111 5 19 MIT 110 6.3 22 ment, states that it shouldn’t be done something is impossible or trying infuriating these passive obstruction- progress — which was built upon the Baylor 101 5.6 17 because it is so large instead of simply to prevent something from happen- ists may be, these situations should success of the R01 award mecha- Colorado 97 5.05 26 rolling up his or her sleeves and doing ing. Instead, their adherence to the not deter us from pushing forward. nism and the partnership between Virginia 86 5.5 44 it; or the person who, when you talk status quo, overt dependence on the One of the many valuable lessons individual investigators/mentors and Iowa 85 5.7 36 about implementing policy changes, literature or outright apathy make it I learned in graduate school was that their students. We need to continue UAB 78 6 25 tells you all the reasons why it can’t be impossible to make something there is always a way to get an answer to foster this relationship but do so Total 5000 done instead of raising valid concerns happen. to a question or to make something in creative ways that adapt to our % of Slots Nationally 66% and then working with you to gure Don’t get me wrong; there are happen. I didn’t learn this lesson only rapidly changing landscape. We need Median YTG Top 30 5.73 out how these concerns can be taken many valid reasons that easily could from my adviser but also from the to avoid the temptation to reduce Median YTG Top 10 5.81 into consideration while planning make someone slip into the passive faculty members in our department. the training of creative scientists but 1 See http://grants.nih.gov/training/outcomes.htm#fundedgrants; data are from the version the changes. All of these di erent obstructive mentality. Sometimes, a ey told me that if you know what embrace that their opportunities in posted in 2009; 7,583 total TG slots nationally. scenarios ultimately result in inac- person may simply be afraid of doing the question is that you are trying di erent areas have expanded. 2 National Research Council, 2011. Research Training in the Biomedical, Behavioral, and tion, which causes projects, labs and an experiment for fear that the results to answer, and if you know what Editor’s note: e authors of this Clinical Research Sciences. e National Academies Press. institutes to stagnate. will disprove a hypothesis. Other 3 techniques are available to develop article wrote on behalf of the AMGDB See http://www.brimr.org/ data from 2009. e word “impossible” can be times, someone may be afraid of leaders who contributed to and endorse an experiment to address the ques- very surreptitious and insidious, and doing that large experiment for fear tion, then there should be nothing the report, including David Harris, University Cancer Center; Kevin Bruce J. Nicholson ([email protected]) is it comes in various active forms, that, if it doesn’t work, money and standing in your way of getting that Boston University School of Medicine; Raney, University of Arkansas for Med- a professor and the chairman of the biochemistry which include the words “can’t” and time will have been wasted. Regard- department at the University of Texas Health answer. If there are technical dif- Michael Ostrowski, e Ohio State ical Sciences; Leslie Parise, University “shouldn’t.” However, it also comes in ing policy and change, some people University; Jane Azizkhan-Cliord, of North Carolina School of Medicine; Science Center at San Antonio and president- culties, then it is your job to think elect of the Association of Medical and Graduate many passive forms, veiled in state- just don’t like or are afraid of change, creatively about the process, talk to Drexel University College of Medicine; and Michael Mathews, Rutgers New Departments of Biochemistry. Richard L. Eckert ments like “at’s not the way things regardless of whether it’s for good or others to get input and devise a way Vadivel Ganapathy, Georgia Regents Jersey Medical School. ([email protected]) is a professor and have always been done,” or “Well, bad. the chairman of the biochemistry and molecular to approach the question from a dif- biology department at the University of Maryland nobody has ever shown this before,” Finally, it’s possible that academic ferent perspective. Sometimes you are REFERENCES or, at worst, “Nothing ever changes politics may be at play, and no mat- School of Medicine and the president of the not able to get a direct answer, but 1. Alberts, B. et al. Proc. Nat. Acad. Sci. USA 111, 5773 – 5777 (2014). Association of Medical and Graduate Departments around here, so why even bother?” ter how good a plan may be, these of Biochemistry. 2. http://acd.od.nih.gov/biomedical_research_wgreport.pdf ese latter forms are examples of politics will work against you simply CONTINUED ON PAGE 45

42 ASBMB TODAY SEPTEMBER 2014 SEPTEMBER 2014 ASBMB TODAY 43 OUTREACH Scientists talking genetics with the public By Joseph P. Tiano

am a second-year postdoctoral which to volunteer, because I enjoy fellow at the National Institutes teaching and it is very rewarding to Exhibit calendar I of Health and one of two dozen watch kids have fun while learning scientists from around the Washing- genetics. Sept. 27, 2014 – Jan. 4, 2015 ton, D.C., area who have volunteered A couple of the hands-on activities Reuben H. Fleet Science Center at the National Museum of Natural the Genome Zone o ered were San Diego History’s genomics exhibit. • the phenylthiocarbamide, or Jan. 22, 2015 – April 27, 2015 I have learned a lot from my time PTC, taste test to identify which vari- e Tech Museum of Innovation IMAGES COURTESY OF DONALD E. HURLBERT AND JAMES DI LORETO, SMITHSONIAN as a genome exhibit volunteer. From ant of the taste receptor TAS2R38 the San Jose, Calif. interacting with 1,500-plus visitors visitor has and I feel very fortunate to have been museum’s Hall of Human Origins. I of you living in other cities, seek out over the past year, I have gained • the trait tree to identify mono- May 15, 2015 – Sept. 10, 2015 employed at the NIH during the look forward to the new challenges it opportunities at your local museum or unique insights into the lay public’s genic traits (dimples, widows peak, St. Louis Science Center year that the genome exhibit spent in presents. science centers. Chances are good they understanding of genetics and expec- tongue rolling) that the visitor may or St. Louis, Mo. Washington. Had I not received NIH While the exhibit left D.C. earlier will be glad to have your help and tations for how genetics will shape may not share with other visitors. e-mails asking for employee volun- this month, it will travel around the your expertise. Oct. 2, 2015 – Jan. 3, 2016 the future. And I have to say that, e trait tree is most fun with teers, I never would have thought U.S. for the next four years. If you as a Ph.D. scientist who spends a lot children and their parents, because it Oregon Museum of Science & to seek out volunteer opportuni- are lucky enough to live in one of the Joseph P. Tiano (tiano233@ of his time inside a scientic bubble usually ends up turning into a com- Industry ties at museums. In fact, I enjoyed cities hosting the exhibit, I highly Portland, Ore. hotmail.com) is a postdoctoral with other Ph.D.s, I was surprised to petition between the parents to see volunteering so much that as the recommend reaching out to that fellow at the National Institute realize just how far out of touch I had who shares more traits with their kids. genome exhibit in D.C. came to a institution and asking about volun- of Diabetes and Digestive and Jan. 28, 2016 – April 25, 2016 Kidney Diseases in Bethesda, Md. become with the lay public’s knowl- But it is also the perfect opportunity Discovery World Milwaukee close, I asked to be transferred to the teer opportunities. For the majority edge and views of science. (And I have to break out the Punnett square and Milwaukee, Wis. been inside my scientic bubble for teach inheritance. only eight years!) e most popular — and most dif- Sept. 30, 2016 – Jan. 1, 2017 In the summer of 2013, to com- cult — hands-on activity is known as Exploration Place PROFESSIONAL DEVELOPMENT CONTINUED memorate the 10-year anniversary Genes in a Bottle. It involves making Wichita, Kan. of the sequencing of the human a necklace with DNA extracted from CONTINUED FROM PAGE 43 of its forms. is will not be easy. It compromise that incorporates ideas Jan. 28, 2017 – May 29, 2017 genome, the NIH and the museum a visitor’s cheek cells. Imagine 20 visi- instead the answer is derived circum- has inltrated our lives and our men- from both sides. Peoria Riverfront Museum partnered to put on the entertaining tors of all ages who have never been in stantially from multiple experiments. tality too deeply, and rooting it out By putting our fear aside, by dedi- Peoria, Ill. and highly educational exhibit titled a lab before sitting around three tables However, it is still an answer. will take serious attitude adjustments cating ourselves to the hard work, by developing a positive attitude, and, “Genome: Unlocking Life’s Code.” with 50-ml conical tubes, Pasteur Sept. 30, 2017 – Jan. 1, 2018 e same can be said for ideas and for many of us. Of course, it is easier to sit back when necessary, by putting our pride e 4,400-square-foot exhibit features pipettes and small cups of their spit. Science North change. People see what policies they on the shelf to compromise and work seven areas of genomic science, It can get a little messy, but it is worth Sudbury, Ontario would like to implement or change. and say something can’t be done exploring what a genome is, the role it when they say in amazement, “You ey know the processes they need to rather than actually rolling up your together, great changes and great of genomics in understanding human mean this white, gooey-looking stu use to implement the change. Some- sleeves and doing the hard work, be it advancements can and will happen. evolution and the role of genomics in is my DNA?” lack — in an engaging, exciting and times there are valid reasons why the that scary experiment, that labor- or reshaping medicine. Museums are great venues to easy-to-understand manner. e most processes originally thought of are time-intensive experiment, or work- What really makes this exhibit communicate science to kids and not feasible. However, that is when ing for institutional change. Also, Andrew D. Hollenbach (aholle@ important lesson I learned was how lsuhsc.edu), author of the book special, I think, is the Genome Zone the public because they are fun and bad I actually was at communicating communication needs to happen to sometimes it means that you have “A Practical Guide to Writing a area, where hands-on activities teach low-pressure environments. ey also science to kids and nonscientists. I am reveal what these reasons are and to to be willing to listen to people who Ruth L. Kirschstein NRSA Grant,” kids and adults alike about genet- o er great opportunities for scientists happy to say that, thanks to volun- think creatively about other avenues oppose change or have competing is an associate professor in the ics and how it is shaping all of our to learn how to communicate science teering, I have dramatically improved to achieve the desired change. interests, communicate with them genetics department at Louisiana State University Health Sciences Center in New Orleans. futures. It is also my favorite area in to the public — a skill most scientists my communication skills. We need to ban the “I” word in all and then work with them to derive a

44 ASBMB TODAY SEPTEMBER 2014 SEPTEMBER 2014 ASBMB TODAY 45 OUTREACH HEY, RESEARCHER! leave that blot alone! Good practices for preparing publication-quality figures ASBMB grants help UAN chapters do outreach 1. Before preparing figures, read the Journal’s Instructions for Authors. By Georey Hunt 2. Adjust brightness/contrast equally across image. Enhanced contrast of one area Enhanced contrast equally across image BAD GOOD he American Society for Hendrix College will bring use amino-acid builder kits to teach Biochemistry and Molecular student presentations and biology fundamental concepts in biochem- T Biology Public Outreach Com- tutoring sessions to underserved istry to local middle-school students mittee has undertaken a number of students at Wonderview High School from underserved communities. increased contrast initiatives to promote and organize in Hattieville, Ark. Wisconsin Lutheran College science-outreach activities in com- Northeastern University will work supported student attendance at its annual Synthetic Biology Summer munities across the country. e most with the Northeastern Program for 3. Spliced image must include dividing line at the splice junction and be described in the Figure Legend. recent venture was a novel partner- Teaching by Undergraduates, known Camp in Milwaukee. ship with the ASBMB Undergraduate as NEPTUN, to organize and teach a While this grant program is only Aliate Network, a chapter-based series of science-themed classes aimed one part of a broader e ort to involve BAD GOOD consortium of more than 90 insti- at local high-school students. ASBMB members in science out- tutions. Participation in science Otterbein University will host a reach, the dedication and passion outreach is a requirement for UAN molecular biology-themed exhibit at of our undergraduate members are splice chapters, so the partnership was a the annual Westerville (Ohio) Starry encouraging indicators for success. natural t. But to spice the pot, the Night Family STEAM Festival. Even better, participation in these activities will instill an interest in outreach committee worked with the Purdue University will host 4. Do not make adjustments that hide any part of the image, including erasing background. UAN to develop a grant program that molecular biology-themed exhibit outreach that will (hopefully) endure would allow chapters to apply for up booths at Purdue Spring Fest and throughout their careers, wherever to $500 to facilitate student partici- Celebrate Science Indiana and will they end up. Read more about the BAD GOOD pation in outreach activities. make regular visits to local K – 12 undergraduate outreach grant pro- Ultimately, chapters at seven science classes. gram at http://bit.ly/Wj5CI5. schools won funding this year. Some e University of Tampa will Geoffrey Hunt ([email protected]) are continuing programming that conduct molecular biology experi- is the ASBMB’s public outreach they have been part of previously, ments alongside students from Tampa coordinator. Follow him on Twitter while some are starting new pro- (Fla.) Preparatory High School. at twitter.com/thegeoffhunt. 5. Avoid excessive contrast adjustment that removes background. grams: e University of San Diego will BAD GOOD

6. Final figures must be high-quality TIFF or EPS files. Avoid preparing figures in PowerPoint to avoid loss of image resolution.

BAD GOOD

Sponsored by the International Society for Hyaluronan Sciences June 7-11, 2015 Details at www.ISHAS.org

46 ASBMB TODAY SEPTEMBER 2014 SEPTEMBER 2014 ASBMB TODAY 47 48 ASBMB TODAY SEPTEMBER 2014