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September 2009

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AnaheimAd FINAL.indd 1 6/15/09 1:00:42 PM contents September 2009 On the Cover: A look at the history of the ASBMB Annual society news Meeting. 2 President’s Message 22 6 News from the Hill 9 Washington Update 10 Retrospective: Ephraim Katchalski Katzir (1916-2009) JBC minireview 13 JBC Highlights Computational series looks at computational Biochemistry biochemistry. 14 Member Spotlight 13 special interest 16 Lifting the Veil on Biological Research 18 Mildred Cohn: Isotopic and Spectroscopic Trailblazer 22 History of the ASBMB Annual Meeting 2010 annual meeting 26 The Chemistry of Life A profile of 28 New Frontiers in Genomics ASBMB’s first and Proteomics woman president, Mildred Cohn. 30 Hypertension: Molecular 18 Mechanisms, Treatment and Disparities departments 32 Minority Affairs 33 Lipid News 34 BioBits 36 Career Insights 38 Education and Training resources Scientific Meeting Calendar erratum online only The article on the 2009 ASBMB election results in the August issue of ASBMB Today mistakenly identified Charles Brenner as professor and head of the Biochemistry Department at Dartmouth Medical School. He is, in fact, head of biochemistry at University of Iowa’s Carver College of Medicine.

September 2009 ASBMB Today 1 president’smessage A monthly publication of The American Society for Biochemistry and Molecular Biology Wimps? Officers Gregory A. Petsko President Suzanne R. Pfeffer President-Elect What Wimps?* Mark A. Lemmon Secretary Merle S. Olson Treasurer BY GREG PETSKO Council Members Dafna Bar-Sagi Ruma V. Banerjee Benjamin F. Cravatt Joan A. Steitz Thomas E. Smith Ann M. Stock hey arrive the last week of August on college campuses James A. Wells Adrian Whitty Tall over the U.S. Accompanied by anxious, hovering Ex-Officio Members parents (indeed, the term “helicopter parents” has entered the lexicon), they spill Ellis Bell Chair, Education and Professional out of rented vans and SUVs, looking bewildered and much younger than their Development Committee years. They are the freshmen, the entering university students who are about to Joan W. Conaway Chair, Meetings Committee experience, for the first time in their lives, the thrill of independence. John D. Scott Chair, Membership Committee Or are they? Increasingly, American college students are going through their Craig E. Cameron 4 years of higher education—and often years more beyond that—still firmly Chair, Minority Affairs Committee Laurie S. Kaguni attached to the parental umbilical cord. It’s an invisible umbilical cord—you 2010 Annual Meeting Program Coordinator probably call it a cell phone—but it’s an umbilical cord nonetheless. It’s not that William C. Merrick Chair, Public Affairs Advisory Committee unusual for some third- and fourth-year students at university to call or text their Toni M. Antalis Chair, Publications Committee parents several times a day. Some of these calls are simply to share the most Herbert Tabor mundane details of their daily lives, but a large number of them are to ask advice Editor, JBC Ralph A. Bradshaw on everything from what courses they should be taking, to what activities they A. L. Burlingame should join, to what they should do about a roommate who snores. Co-editors, MCP Edward A. Dennis This is completely different from my college experience, and, I suspect, the Joseph L. Witztum college experience of practically everyone in my generation. True, we didn’t Co-editors, JLR have portable communication devices, but I don’t think it would have made any ASBMB Today Editorial Advisory Board Alex Toker difference if we had. We didn’t want to be in constant contact with our parents. Chair We went away to college, in part, so as not to be in constant contact with our Greg P. Bertenshaw Craig E. Cameron A. Stephen Dahms Irwin Fridovich parents. What’s more—and this is the key point, I think—our parents didn’t want Jonathan Gitlin Richard W. Hanson to be in constant contact with us. Okay, one time when I hadn’t phoned home Elizabeth A. Komives Bettie Sue Masters Luke A. O’Neill Duanqing Pei for more than a week to reassure my folks that I was still alive and spending Carol C. Shoulders Robert D. Wells their hard-earned tuition money, when I finally did call, reversing the charges as ASBMB Today usual, my father, on being asked by the operator if he would accept a collect call Nicole Kresge Editor [email protected] from his son Greg, replied, “I have no son named Greg. I used to have one, but Nick Zagorski Science Writer we haven’t heard from him in 30 years,” and hung up. But that was an extreme [email protected] situation. The point is, if I had suddenly started phoning home three or four times Nancy J. Rodnan Director of Publications [email protected] a day, my mother would have called the university health service to get them to Barbara Gordon Executive Director find out what was wrong with me, and my father would have called the campus [email protected] police to get them to find out who was impersonating their son. And most of Magazine design & production: Amy Phifer their contemporaries would have reacted the same way. For information on advertising contact A few years ago, psychologist Hara Estroff Marano wrote an article in Capitol Media Solutions at 800-517-0610 or [email protected] Psychology Today called “A Nation of Wimps.” (You can find it at www.psy- chologytoday.com/node/21819 and I urge you to do so; it’s worth reading.) In it, he argues that we are in danger of raising a generation of Americans who are unable to think for themselves, who have a distorted view of the world as www.asbmb.org a dangerous and hypercompetitive place, who are accustomed to gaming the system because their parents have bought or finagled special privileges for them throughout their childhood, and whose self-esteem is consequently nowhere near what it should be. Here are a couple of excerpts:

2 ASBMB Today September 2009 president’smessage

“Behold the wholly sanitized childhood, without skinned Now, I don’t want to fall into the trap of making over- knees or the occasional C in history. Kids need to feel generalizations, something I think Marano is guilty of in that badly sometimes,” says child psychologist David Elkind, article. Many students today are well-adjusted, capable, professor at Tufts University. “We learn through experi- and independent young men and women. I meet them ence, and we learn through bad experiences. Through all the time. What I’m trying to say is that I have noticed failure, we learn how to cope.” Messing up, however, even an increase in the number who are not, and that increase in the playground, is wildly out of style. Although error and seems to be correlated with an increase in what I would experimentation are the call over-parenting. It’s also correlated with a true mothers of success, sharp rise in the number of students who are parents are taking pains Increasingly, documented to have some sort of learning to remove failure from the American college disability, and who, therefore, are entitled to— equation… “ students are going and always request—special accommodations “No one doubts that on tests and quizzes. I’m deeply sympathetic there are significant through their 4 years to any student with a legitimate difficulty that economic forces push- of higher education— they are trying to overcome, but I worry that ing parents to invest so at least some students have been placed into heavily in their children’s and often years more a category in which they don’t belong by their outcome from an early beyond that—still firmly parents and educators as a way of helping age. But taking all the attached to the parental them do better, and consequently, they never discomfort, disappoint- develop the confidence in their own abilities ment, and even the play umbilical cord. that they will need when they face a world out of development, that won’t make any special accommodations especially while increasing pressure for success, turns out for them whatsoever. So, if you allow for the somewhat to be misguided by just about 180 degrees. With few chal- ”sensational tone of the article, I think Marano has some lenges all their own, kids are unable to forge their creative important points to make. adaptations to the normal vicissitudes of life. That Of all the virtues to not only makes them risk-averse, it makes them which I aspire, high on psychologically fragile, riddled with anxiety. In the Whether we want the list would be self-reli- process they’re robbed of identity, meaning, and a ance. I take pride in being sense of accomplishment, to say nothing of a shot to or not, we’re on able to repair computers, at real happiness. Forget, too, about perseverance,“ our way to creating a fix electrical problems, do not simply a moral virtue but a necessary life skill. nation of wimps. basic plumbing, and build These turn out to be the spreading psychic fault some of my own furni- lines of 21st century youth. Whether we want to or ture. Until cars became not, we’re on our way to creating a nation of wimps.” rife with anti-pollution devices and overburdened with I’ve taught college freshmen for almost 30 years, and complex electrical systems,” I did a lot of my own automo- let me tell you, I think for many of our youth that ship has bile work, as did many people of my, and particularly my already sailed. During the past couple of decades, I have father’s, generation. I like not having to depend on others seen students on average become less independent and any more than is absolutely necessary, and I don’t mind more fearful, indecisive, and risk-averse. Many of them making mistakes. But I suspect, if Marano is right, that this have been so suffocated by their parents and so insulated is one of many respects in which I am about to become as from even the slightest disappointment by well-meaning, uncommon as a wooly mammoth. but ineffectual, educators that they are likely to be locked Yet there is one place where you can still find young in a state of adolescence for years after they graduate. people who take risks, think for themselves, and perse- And because they’ve never learned how to handle defeat vere. That place is anywhere you find a junior faculty mem- and discouragement, they are also prone to depression ber in the sciences. We may be about to become a nation and acute anxiety when suddenly confronted by difficul- of wimps, but the ranks of the instructors and assistant ties: in school, in relationships, and in life choices. professors constitute a wimp-free zone.

September 2009 ASBMB Today 3 president’smessage continued It has become a cliché that, as we get older, we tend years, of failure. Tough enough to get turned down when to look down on young people as having a much easier you’ve at least had the experience of some success. But time of it than we did. (I’ve caught myself about to say, to to be told repeatedly that your proposal hasn’t made the some graduate student complaining about a shortage of grade when you’re just setting off on your own would pipette-persons, “When I was your age, we didn’t have break many a weaker person. And let’s not forget, as I pipettemen; we blew our own glass pipettes, and we just pointed out, that we are forcing these young people made the glass from sand as well!”) That attitude couldn’t to publish their papers in journals with astronomically high be more inappropriate rejection rates, thereby exposing them to in the case of scien- regular pummeling from inexperienced edi- tists just starting their …we are forcing these tors and misanthropic reviewers. academic careers. young people to publish But, you say, at least they have help Beginning investiga- “ their papers in journals from of those of us who have already been tors have a much through the mill. Not necessarily. I know of more difficult time than with astronomically many institutions where the senior faculty we did, in just about high rejection rates, members deliberately take a “hands-off” every aspect of aca- approach with younger colleague—a sort demic life. It’s so much thereby exposing them of “sink-or-swim” philosophy that man- harder to get funding, to regular pummeling dates simply observing whether someone for one thing. We went from inexperienced has the right stuff to make it on their own. through some troughs I believe this distancing is often well-inten- in federal support for editors and misanthropic tioned, because inviting a junior faculty science when I was reviewers. member to collaborate can be the kiss of starting out, but noth- death: at many schools, if a non-tenured ing like the doldrums of the past 7 years. Competition is investigator has worked extensively with senior colleagues, fiercer for fellowships, young investigator awards, and all when they are brought up for tenure, they are tarred with the other little things that help make getting one’s career” the brush of not really having accomplished anything going easier. The number of scientists has increased themselves. dramatically, but the number of such sources of support As if that weren’t bad enough, I’m not even sure our has not. junior colleagues get enough sympathy from their elders— Genomics hasn’t made things easier. It’s the main rea- at least, not in a form that does them much good. At son that biology has become a technol- precisely the time they ogy-driven science, which means that, It’s a miracle more of need encouragement, to play at a high level, the cost in equip- not just about their ment alone can be very high. So not them don’t chuck it all and own work but about only does the aspiring genome biologist “ go into a career with better the future of profession have to raise money in an era of tight they are so eagerly funding, he or she has to raise more prospects, like selling land- trying to join, what than the average senior faculty member line telephones. they are most apt to in many other fields. hear from us is a litany The bar is also much higher in terms of what is of complaints about how difficult things are and how bleak expected in order to gain recognition—and, eventually, that future looks. It’s a miracle more of them don’t chuck it all and go into a” career with better prospects, like selling tenure. “Publish or perish” has become “publish in one of a handful of journals with a high impact factor or perish.” I land-line telephones. had the luxury, when I was getting established, of pub- So let me offer a few suggestions for things we all lishing my papers in the places I thought they belonged, could do to make their struggles just a bit easier and which often included highly specialized journals. Heaven their burdens a tad lighter. First and foremost, we should help the young biologist who does that now. abandon, as a matter of policy, the senseless, haughty, Then there are the daily discouragements, which are and counterproductive belief that they must do everything more numerous, I think, than those we suffered at their on their own. Institutions should reward young scientists age. Because it’s harder to get grants today, the average who collaborate effectively with their senior colleagues for young investigator must endure several rounds, and often helping to knit departments and programs together, not

4 ASBMB Today September 2009 president’smessage continued penalize them for failing to demonstrate some macho- have anything negative to say about the substance of driven concept of “independence.” the proposal but is merely trying to assert his or her own Second, we should be wary of what sort of impres- superiority. It’s inexcusable behavior. If you really think the sion our own carping makes on our young associates. science is exciting but the investigator has proposed far Remember, we are who they want to become, and if they more than they can do in the time allotted on the grant for see us as dissatisfied, shrill, and constantly frustrated, the money they have requested, fund the damn thing and even the best of them may have second thoughts about let them find out by experience how much can be done getting to where we are. I’m not saying we must give up in 4 years time. To force them to resubmit an otherwise complaining—at my university that’d be like suggesting good proposal just to remove some specific aims gives that a koala bear give up eucalyptus leaves. But let’s do the impression that their senior colleagues are a bunch of our complaining to each other, and remember that one nit-picking, supercilious jerks. Which we probably are, but of the most important things we have to give to our junior it’s nothing to be proud of. faculty (and eventual successors) is a sense that this is a Finally, we should not forget to express to junior life worth living and a career worth fighting for. We have to faculty everywhere our sympathy and understanding for help them keep hope alive. what they’re going through, and our gratitude that they Third, we must, as a community, condemn the prac- have chosen to endure it. Because without them, our line tice of trashing research proposals from beginning inves- would be extinct, and the fire of science would die out. tigators as “overly ambitious.” I’ve seen this ploy used Applaud them for their dedication, aspiration, and, above frequently and it always makes me furious. Being ambi- all, their fortitude. Because they are anything but a bunch tious is what got us where we are. It’s what drives much of wimps. of the great science. It’s a virtue, not a vice. I suspect that, when this charge is made, the reviewer actually doesn’t *Reprinted with permission from Genome Biology (2009) 10, 109.

September 2009 ASBMB Today 5 news from the hill Former Minority Leader Bob Michel to Receive Schachman Award BY PETER FARNHAM

ormer Illinois representative and House Minority major focus. He was a key member of the Campaign for FLeader Robert H. “Bob” Michel has been selected as Medical Research (CMR), and in the mid- to late-1990s, ASBMB’s 2010 recipient of the Howard K. Schachman he, along with his former congressional colleague Paul Public Service Award. In a letter to Michel announcing his Rogers, participated in hundreds of meetings on Capitol selection, ASBMB President Greg Petsko said: Hill to try to persuade the Congress to support a doubling “ASBMB offers you this award not only in recogni- of the NIH budget. tion of your many years of service in the Congress of Observers who attended those meetings said that no the United States but also to recognize your efforts over matter how obstinate the member was with whom they the past decade to increase public and congressional were talking, Michel remained true to his genial and gentle support for the National Institutes of Health. Your work during and after the campaign to double the size of the NIH budget was carried out in the true spirit of public service which the Schachman Award strives to recognize. Your tireless advocacy for NIH, particularly during a time of great stress on the federal budget, was instrumental in the successful completion of the doubling campaign.” Michel was born and raised in Peoria County, Illinois. His public service began at an early age, when he served as a World War II combat infantryman with the 39th Infantry Regiment in France, Belgium, and Germany. He was wounded by machine gun fire during his combat tour and was awarded the Purple Heart and two Bronze Stars. Upon his discharge from military service in 1946, he received a bachelor’s degree from Bradley University, in Peoria, and his public service continued when he served as adminis- trative assistant to the district’s congressman, Harold Velde, from 1949 to 1956. Michel was elected as a Republican to the seat held by his former employer in 1957 and served 18 consecutive Congresses—a total of 38 years— finally deciding not to run for reelection at the conclusion of the 103rd Congress in 1994. Michel served as his party’s leader in the House of Representatives from the 97th through 103rd Congresses. However, it was after his service in the Congress that biomedical science became his

6 ASBMB Today September 2009 news from the hill

nature. Others who have accompanied Michel on Hill keepsake, as well as an honorarium and an opportunity visits note how everyone seems to know him, and when to deliver a lecture at a Society function. The Public Affairs going to a meeting with him, one has to allow extra time Advisory Committee plans to present the Award to Michel to accommodate the many people who want to stop and on September 21 in Washington, D.C. talk to him in the halls of House office buildings as he On behalf of the Society, ASBMB Today offers its con- passes by. gratulations to Michel on his receipt of this award. Bill Brinkley, former chairman of the Public Affairs Advi- sory Committee, was very active in the CMR in the late Peter Farnham is Director of Public Affairs at ASBMB. He can be 1990s and early 2000s. Brinkley reports that “I went on reached at [email protected]. many, many trips to the hill that CMR arranged in those days, and Bob introduced me to almost every signifi- cant member of Congress at the time. He could open doors that no one else could open. Everyone would stop Third Science Policy and chat. He would always introduce me and ask if the Fellow to Start in August congressman could talk to me, and often it would happen ASBMB’s third Science Policy Fellow, Kyle Michael spontaneously without an appointment. Bob was dedi- Brown, began his fellowship at Society headquarters in cated to biomedical research, and he played a vital role in Bethesda on August 17. Although Brown is only begin- the doubling campaign.” ning his policy career, he brings a strong background in “Bob Michel is a giant and will serve as a fine role public policy to the job. He double majored in biology model for future Schachman awardees. He has done a terrific job for medical sciences,” says Robert D. Wells, and government as an undergraduate at Georgetown former ASBMB president, who worked with Michel on the University and met with congressional staff during his doubling campaign during his presidency. years in Washington on science policy-related issues. On January 18, 1989, outgoing President Ronald As a Ph.D. student at Harvard University (he earned his Reagan conferred upon Michel the Presidential Citizens doctorate in evolutionary genetics this past May), he Medal, the second highest civilian award given, making provided science advice to a Massachusetts state sena- th him the 7 recipient of the honor. On August 8, 1994, tor and testified in the Massachusetts State Legislature he was awarded the Presidential Medal of Freedom, the on safe alternatives to toxic chemicals. He also worked highest civilian award in the United States, by President on policy and funding issues with the American Institute Bill Clinton. While in Congress, Michel was the usual starting of Biological Sciences in 2007 and 2008, receiving an pitcher on the Republican side during the annual Demo- Honorable Mention for one of the AIBS’s Emerging Pub- crats versus Republicans baseball game. lic Policy Leader Awards in 2007. ASBMB is delighted to Michel is memorialized in his district by The Bob Michel have Brown join the staff, and readers of ASBMB Today Bridge, carrying Route 40 across the Illinois River in Peo- will soon be seeing his byline in the magazine. ria. In addition, his alma mater, Bradley University, named The ASBMB Science Policy Fellowship was estab- the Student Center after him. Finally, in the Capitol, the lished in 2007 and has proven to be a valuable addition second floor suite of offices occupied by the Speaker to the Society’s public affairs program. The Fellowship is were designated the Robert H. Michel Rooms by the open to new Ph.D.s. The fellow comes to Washington, House in 1995. The Schachman Award recognizes an individual who D.C. and spends 15–18 months working on public policy best demonstrates dedication to public service in sup- issues in ASBMB’s offices in Bethesda. If you know port of biomedical science, as exemplified by the award’s a student who might be interested in applying for the namesake, Howard K. Schachman, who served as upcoming fellowship term (which will begin in the late chairman of ASBMB’s Public Affairs Advisory Committee summer or early fall of 2010) please have them contact for more than 10 years. The Award is given annually, and ASBMB Director of Public Affairs Peter Farnham at candidates are considered by the Society’s Public Affairs [email protected]. Advisory Committee. The award consists of a permanent

September 2009 ASBMB Today 7 news from the hill continued Quantifying the Benefits of Research BY ALLEN DODSON

iomedical research draws broad popular and Putting the Numbers Bbipartisan support on the promise of cures for to Work for Research diseases and the improvement of human health. Focus group testing by FASEB has shown that aver- With the economic circumstances of the last year, age Americans do not know that NIH is a research however, research has taken on a new significance funding agency. NIH lacks the pop culture exposure for its more immediate impact. Combined with a of agencies like the Centers for Disease Control and strong push for transparency and online access, new Prevention and the Food and Drug Administration. tools and methods that have appeared in the last Americans who have heard of NIH believe that it is pri- few months have added a major new tool for policy marily responsible for making public health announce- advocacy. ments, or, if they know that the agency conducts research, believe that its activities are focused entirely Measuring the “Multiplier” Effect at the campus in Bethesda, Maryland. Research dollars are spent on a multitude of salaries, This lack of public knowledge about NIH creates supplies, and services. The companies that pro- a problem for research advocacy. The Congressional vide equipment and reagents make purchases from committees that oversee NIH must choose directly their suppliers and pay their own sales and support between funding for research and other visible public employees. These salaries are spent as well, on cars priorities like education and healthcare. Without a and appliances or trips to the local coffee shop. In greater understanding that funding for NIH sup- this very qualitative way, it makes sense to imagine ports jobs in research and future cures all around the that a dollar spent on research can have more than a country, it is difficult for even the most sympathetic dollar’s worth of effects on the economy. The ques- Congressmen to make that tradeoff. tion was how to quantify this “multiplier effect.” Now, more than ever, researchers have access In June of 2008, the healthcare advocacy group to information that can make the case for research. Families USA attempted to put their fingers on the While it is important to pass that information along to hard numbers, in a report titled “In Your Own Back- Congress it is equally important for the general pub- yard: How NIH Funding Helps Your State’s Economy.” lic to hear about the benefits of biomedical research. The report contains details of jobs that are possible For perhaps the first time, regular researchers have because of NIH research and on the business activity access to the information they need to make that multiplier for each of the 50 states. case in newspaper op-ed letters and public dis- cussions. This knowledge is the power to secure Reporting the Results increased support for biomedical research in the Perhaps equally valuable is a new push by the major future. funding agencies to make information on awards available online. NIH recently revamped its Research Allen Dodson is an ASBMB Science Policy Fellow. He can be Portfolio website (RePort), and with a few mouse reached at [email protected]. clicks, you can identify research in a specific disease area or work done within a given state or Congres- Resources sional district. The Families USA report: This newly enhanced database arrived just in http://tinyurl.com/7eq7oz time for the passage of the American Recovery and NIH’s RePort site: Reinvestment Act (ARRA) and its billions of dollars http://report.nih.gov/ in research funding. The new NIH database allows A similar database for the for specific searches of recovery act projects, giving National Science Foundation: research advocates a very concrete way to measure www.nsf.gov/awardsearch the benefits of the stimulus legislation.

8 ASBMB Today September 2009 washington update FASEB Congress Extends SBIR Program as Details Are Negotiated BY CARRIE D. WOLINETZ

he House and the Senate both passed bills this one area of research at the expense of all others, we Tsummer to reauthorize and improve the Small Busi- urge you and your colleagues in Congress to increase ness Innovation Research (SBIR) and Small Business funding for all research agencies, thereby increasing Technology Transfer (STTR) programs but were unable the total investment in SBIR and other projects,” he to reconcile differences between the bills in conference. continued. FASEB has also contacted the Office of Of interest to FASEB members, the Senate bill includes Science and Technology Policy (OSTP) in the Execu- an increase of the SBIR funding set-aside from 2.5 tive Office of the President, including OSTP Director percent to 3.5 percent. The set-aside is taken from the John Holdren and co-chairs of the President’s Council budget of 11 research agencies, of Advisors on Science and those whose budgets exceed Technology (PCAST) Harold Var- $100 million, including NIH, NSF, Rather than mus and Eric Lander, as well as the United States Department increasing support activating its grassroots in sup- of Agriculture (USDA), and the port of the House version of the Department of Energy (DoE). “ for one area of bill. FASEB’s efforts have been Although the increase will be research at the profiled in both Science and The gradual, it will boost the alloca- New York Times. tion for the SBIR program by 40 expense of all others, In addition to the differences percent, redirecting $1 billion we urge you and in the set-aside increase, the in research funds into the SBIR House bill contains a provision program. your colleagues in that would allow greater partici- FASEB has led an effort to Congress to increase pation by venture capital backed support the House version of companies in the program. the bill, which passed in early funding for all Although FASEB does not have July, that does not include the research agencies, a position on this issue, it has set-aside increase. On June 23, proven contentious in trying to FASEB joined nearly 100 groups thereby increasing reconcile the two versions and in sending a letter to both the the total investment undoubtedly played a role in the House and Senate opposing the in SBIR and other failure of the conferees to come set-aside increase and urging to agreement. Although the lawmakers to increase federal projects. SBIR/STTR programs were due investment in all research, rather to expire on July 31, Congress than increasing funding for one passed, and the President program at the expense of others. FASEB President signed,” S.1513, an extension of the program through Mark Lively met with staff aides on the House Small September 30, 2009. This temporary extension will Busixness Committee, and reiterated the research allow the SBIR reauthorization pre-conference negotia- community’s concerns about the Senate bill. “FASEB tions between the House and Senate to continue at supports the SBIR program and recognizes the ben- a staff level through the August recess, with a formal efits of the participation of small businesses in scientific conference sometime in September. research,” Lively stated, and noted that there is no cap on the SBIR program, which means that agencies can Carrie D. Wolinetz is Director of Scientific Affairs and Public fund meritorious SBIR applications above the current Relations for the Office of Public Affairs at FASEB. She can be set-aside level. “Rather than increasing support for reached at [email protected].

September 2009 ASBMB Today 9 asbmbnews Retrospective: Ephraim Katchalski Katzir (1916-2009) BY CYRIL M. KAY AND HOWARD K. SCHACHMAN

phraim Katzir, whose creative research was deeply involved as an Officer of the Ein the 1940s had a seminal impact Haganah in the War of Independence on the development of protein sci- leading to the establishment of the ence, died on May 30, 2009 at the State of Israel in 1948. During that age of 93. His pioneering research turmoil, both Katchalski brothers as a graduate student at The received invitations to join the new Hebrew University of Jerusalem Weizmann Institute of Science. led to a new field of science— Ephraim founded the Department the design, construction, and of Biophysics and was its head application of synthetic poly- for many years, while Aharon peptides as models of natural formed the Department of Poly- proteins. Ephraim also played mers, which he headed until his major roles in the founding of the death at the hands of terrorists Weizmann Institute of Science at Ben Gurion Airport in May of and the establishment of the State 1972. Largely as the result of the of Israel of which he was the fourth creative research of the Katchalski President (1973–1978). brothers, the Weizmann Institute The Katchalski family emigrated of Science became internationally from Poland to Palestine in 1922 when renowned and was the launching pad Ephraim was six, and his older brother, for many talented students who earned Aharon, was nine. Both brothers had a deep international reputations. interest in science, graduating from The Hebrew University of Jerusalem. Ephraim’s fascination with the Polypeptides as Models flora around Jerusalem led him to study biology, but he A flood of papers followed Ephraim’s poly-l-lysine article. switched to the newly opened Department of Theoretical Better methods for removing blocking groups from side and Macromolecular Chemistry, where he conducted his chains were discovered, and a variety of polypeptides groundbreaking Ph.D. research with Max Frankel. Their such as poly-l-histidine, poly-l-aspartic acid, and poly-l- studies on the polycondensation of α-amino acid esters proline were synthesized along with different copolymers. to form polypeptides of glycine and alanine resulted in These macromolecules became the subject of research two papers in 1942 (1, 2). But Ephraim, dissatisfied with in physical chemistry laboratories throughout the world. the use of amino acid esters, looked for other derivatives They served as models for optical rotation, circular to make the desired polymers. dichroism, infrared spectroscopy, and x-ray diffraction That search led him to the α-N-carboxyl amino acid studies aimed at determining the structure of polypeptide anhydrides synthesized by Leuchs in 1906, launching chains in proteins and analyzing conformational changes. a new direction for research on proteins. The resulting Tests of theories of the helix-coil transition were based on paper was originally rejected by a Journal of the American experiments with polyamino acids of varying molecular Chemical Society editor who was not convinced that a weights and compositions. Experiments on the “melting” polymer was produced. Months elapsed before it was of helical polypeptides to form random coils were relevant resubmitted with additional evidence and finally published to ongoing investigations of protein denaturation. The in October of 1947 (3). The editor had difficulty fathom- exciting demonstration by Ephraim and his colleagues of ing the reason for this delay, not knowing that Ephraim the cis and trans configurations of the peptide bonds in

10 ASBMB Today August 2009 asbmbnews

poly-l-proline played a major role in elucidating the struc- Education and Training ture of collagen. Their accompanying analysis of the con- While deriving a strong sense of aesthetic pleasure from formations of the polymer in solution demonstrating both his own research, Ephraim also enjoyed involvement with right-handed and left-handed helices proved invaluable in students and protégés. To pay his debt to teachers who much later research on the kinetics of protein folding. The helped shape his aspirations, he developed an extramural striking discovery that certain amino acids had a propen- scientific program for children on Israeli university cam- sity to form α-helices, whereas others preferred β-parallel puses. He also co-edited a popular science magazine or anti-parallel pleated sheets, had a major impact on called Madah (Science) aimed at a youthful audience. research aimed at predicting and determining the struc- Ephraim loved to teach, and it showed; he literally tures of proteins. Studies on highly charged polypeptides radiated enthusiasm in his lectures. His thoughtful and were crucial in the development and testing of theories of creative scientific research attracted many trainees, and polyelectrolyte behavior. Synthetic polypeptides also were he delighted in their development as independent inves- of value in initial investigations of the genetic code, when tigators. Ephraim always considered these individuals as it was shown that the product of cell-free synthesis using a second family, and he was particularly proud that three polyuridylate as messenger RNA corresponded to the former students became department heads at the Weiz- poly-l-phenylalanine that had been synthesized earlier by mann Institute: Avraham Patchornik (Organic Chemistry), chemical means. Michael Sela (Chemical Immunology), and Izchak Stein- An outgrowth of the synthesis of linear polypeptide berg (Chemical Physics). chains was the construction of multichain polyamino acids and polypeptidyl proteins with polypeptide chains Service to the Nation attached covalently to free amino groups. Through these Ephraim had a strong sense of national responsibil- methods, the Katchalski group synthesized polytyrosyl ity, which was reflected in the number of positions he gelatin, and the demonstration of its antigenicity led to assumed in government activities. This included service an outstanding research program on the formation of as Chief Scientist of the Israel Defense Ministry and Chair- synthetic antigens in the laboratory of one of Ephraim’s man of the National Council for Research and Develop- first students, Michael Sela. ment and the Council for the Advancement of Science Education. Immobilized Enzymes In May 1973, the Israeli Knesset elected Ephraim the During the time he was studying synthetic polypeptides, fourth President of the State of Israel. It was then that he Ephraim started constructing “water insoluble enzymes” adopted the Hebrew name Katzir, as his brother Aharon that were fully active catalytically. In 1960, he published had done earlier. His term in office was a difficult one, a paper titled “A Water-insoluble Trypsin Derivative and since it began some four months prior to the outbreak of Its Use as a Trypsin Column” (4) with Atara Bar-Eli. Such the Yom Kippur war and a year after the tragic murder of columns, they noted, could be “employed repeatedly Aharon, who was the original designee to be President. to induce specific chemical changes in relatively large The presidency of Israel is an honorific and ceremonial amounts of substrates.” In preparing this column, Katch- position wherein the incumbent symbolizes moral rather alski and Bar-Eli used trypsin to initiate the polymerization than political leadership for the nation. Ephraim fulfilled of N-carboxy-l-tyrosine anhydride to form water-soluble, that role admirably; he was responsive to the needs of fully active polytyrosyl trypsin. It was then coupled to the people of Israel, who found in their President a deep a diazotized copolymer of p-aminophenylalanine and resonance with their concerns, their pain, their joys, their leucine, leading to the insoluble product used as a achievements, and their dreams. trypsin column. This imaginative adaptation of the various techniques developed in Ephraim’s laboratory was the Post-presidency Research start of a major international activity leading to industrial Following his presidential term of office, Ephraim returned processes. For his contributions in the development of to science at both the Weizmann Institute, as an Institute immobilized enzymes, Ephraim was awarded the first Professor, and the University of Tel Aviv, where he founded Japan Prize in 1985. the Department of Biotechnology. In the 1980s, Ephraim

August 2009 ASBMB Today 11 asbmbnews continued played a major role in the development of biotechnology Below, as a tribute to Ephraim we offer thoughts and that catapulted Israel into the forefront internationally. reflections from several of his friends and colleagues. In his later years at Weizmann, Ephraim investiaged molecular mechanisms of protein interactions between I was one of Ephraim’s first Ph.D. students. He has specific proteins and peptides selected from a random been a great teacher and a close friend for the past 59 peptide library. This approach contributed to a more years. His contribution to science and to the State of precise definition of the structural requirements for the Israel has been enormous. binding of a neurotoxin (bungarotoxin) in the nervous His original development of polyamino acids and system. He also led a group that developed a theoretical protein-protein recognition algorithm (docking) that suc- water-insoluble enzymes has been among his many cessfully predicted the structure of the complex between important contributions to science worldwide. His β-lactamase and the protein inhibitor BLIP, before it optimism in the future of science and its role in the was experimentally determined. Clearly, the novelty of progress of humanity has been paramount, notwithstand- Ephraim’s research continued to the end. ing tragedies in his family. Characteristic of him, were his warm heart, kindness, Honors and Legacy sense of humor, and desire to help others. Ephraim received many honors including membership Michael Sela in the Israel Academy of Sciences and Humanities, the W. Garfield Weston Professor of Immunology Royal Society of London, the U.S. National Academies, Weizmann Institute of Science and the Académie des Sciences in France. He received the Rothschild and Israel Prizes in Natural Science, the It was a wonderful period for us to be graduate Linderstrøm-Lang Gold Medal, the Engineering Founda- students with Ephraim in what was then the newly estab- tion’s International Award in Enzyme Engineering, and he was appointed to France’s Order of the Legion of Honor. lished Biophysics Department at the Weizmann Institute. In addition to his scientific legacy, there are the memo- Ephraim was a true scholar. He showed true respect for ries that we will always treasure: the warm humaneness, other people’s opinion and ideas, often expressing his the unfailing generous spirit, the intellectual honesty and own opinion in Yiddish to clarify his point. generosity, the insatiable curiosity, the possession of an Ephraim’s schedule for a work day was interesting inner strength rarely encountered, and the unflagging and unusual. The day usually started with a meeting with enthusiasm for life. The protein science community has one of the students very early in the morning, studying lost an outstanding researcher, a selfless supporter of the a subject that often was completely unrelated to the scientific enterprise, and an inspirational educator. student’s research. To an outsider, he probably looked His own words provide a beautiful summary of his career: like a checkmate game master who played a simultane- “…I have had the opportunity to devote much ous game against a group of student players. of my life to science. Few activities can be more Scientific writing was done at night, often in a rewarding than conducting research that leads to small group, with the involved partners in the famous a better understanding of the phenomena of life Ephraim’s style, which involved checking and rechecking and nature, and indeed my work in all its aspects— every word until Ephraim was satisfied, regardless of the research, teaching, collaboration with colleagues, tired eyes of the participants. (He never seemed to get and promotion of scientific activities—has brought tired himself.) me great personal fulfillment. “Yet, my participation over the years in activi- It was certainly a privilege to be associated with ties outside science has taught me that there is life Ephraim. His death is a sad loss to all of us. beyond the laboratory. I have come to understand Izchak Steinberg that if we hope to build a better world, we must be Professor Emeritus of Neurobiology Weizmann Institute of Science guided by the universal human values that empha- size the kinship of the human race—the sanctity of human life and freedom, peace between nations, I knew Ephriam as a friend and a scientific collaborator. honesty and truthfulness, regard for the rights of I first met him at a Proteins Gordon Conference in the others, and love of one’s fellows.” 1950s, where I heard his brilliantly delivered and exciting

12 ASBMB Today August 2009 asbmbnews continued lecture on polyamino acids. Later, in December 1959, on also among the founders. Subsequently I did my Ph.D. a return trip from a summer lecture course in Melbourne, research on the interaction of monosaccharides with Australia, I stopped at the Weizmann Institute to visit amino acids under Aharon at his Department of Polymers Ephraim and deliver a lecture in his biophysics depart- of the Weizmann Institute. Soon after, in 1954, Ephraim ment. In 1963, Ephraim graciously accepted me in his took me into his fledgling Department of Biophysics. laboratory during my sabbatical leave from Cornell, and Although he and his colleagues were then fully occupied I have been a steady visitor to the Weizmann Institute in their ground breaking studies of synthetic polyamino almost every year since then, including another sabbati- acids as protein models, he still gave me the freedom to cal leave there in 1970. move to work on carbohydrates and lectins, for which I During all these years, I had very close scientific con- have been ever grateful to him. tact with Ephraim, with much give and take on scientific Ephraim would often tell us that doing basic research issues, on Israeli politics, and other topics, either in in Israel is a special privilege and that it is justified only his office or in his home on the campus. We had many if it is of the highest level. He also used to say that overlapping scientific interests and challenged each other scientists in Israel must take an active part in contribut- with problems at the frontier of our field. This relation- ing to the solution of national problems, for example in ship continued even in his home in Jerusalem when he education, technology, or industry. He not only preached became President of the State of Israel. As President, but also acted; his pinnacle was his service as Israel’s Ephraim convened many scholarly discussion groups, President. to which he invited me. It was there that I met many of Nathan Sharon university intellectuals and Israeli government officials and Weizmann Institute of Science benefited from wide-ranging discussions there. Ephraim was the father of the field of polyamino acids, Ephraim taught a course in biophysics in 1962 that including his studies of the synthesis and physical and included laboratory experiments. The course was given biological properties of these biopolymers. He had a at The Hebrew University of Jerusalem, where I com- vivid imagination that enabled the field to make leaps of pleted my M.Sc. thesis, and the laboratory experiments progress at many stages of its development. His inter- were conducted at The Hebrew University of Jerusalem national stature as a scientist brought honor and fame and the Weizmann Institute. The course opened my to the Weizmann Institute and to the State of Israel. I am eyes to macromolecules, mainly polyamino acids. It very pleased to have known him and am saddened only was a fascinating time in macromolecular biochemistry in never again being able to drop into his home on the because polyamino acids were the only pure molecules campus for coffee and exciting discussions. that mimicked proteins and whose properties could be Harold A. Scheraga studied in a precise manner. I therefore came to the George W. and Grace L. Todd Professor conclusion that one could utilize polyamino acids also of Chemistry, emeritus, Cornell University as models for enzymes, so I moved to the Weizmann Institute where the action was. I wanted to generate a Looking back at my career, it is clear to me that I have model enzyme, so I, together with Israel Pecht, gener- been extremely fortunate in having had Aharon and ated a complex between Cu(II) and polyhistidine and Ephraim as mentors and friends. Both brothers were proved that this complex indeed behaved as an oxidative gifted and broad-minded scientists, original thinkers who enzyme. Ephraim was immensely impressed with this made seminal contributions, each in his respective area, finding because it was a proof that polyamino acids Aharon in polymer science, Ephraim in protein research. can mimic enzymes. He therefore hooked me up with They were mesmerizing speakers and inspiring teachers Arieh Berger, a great enzymologist at the Department of with friendly and warm personalities. I first came to know Biophysics, with whom I finished my Ph.D. them in 1948, during the Israel War of Independence, Alexander Levitzki when I served under their command in the Scientific Wolfson Family Professor of Biochemistry Corps of the Israel Defense Forces, of which they were The Hebrew University of Jerusalem

August 2009 ASBMB Today ex13 asbmbnews continued Ephraim was my postdoctoral mentor from 1971 to in Israel at large, succeed in recruiting excellent, top 1972. He gave me the greatest time of my life, scientifi- candidates for faculty positions. “Getting bright people cally speaking, as his office was always open to me, and is so important for our future,” he added. That was two his mind was always receptive to discussing scientific hours before his death. ideas. I think Ephraim’s great success as a scientist Benny Geiger was embodied in the four enduring lessons I learned Dean, Faculty of Biology Department of Molecular Cell Biology from him: 1) words matter; 2) use synthetic chemistry Weizmann Institute of Science to study biological problems; 3) know and love your system; and 4) build a team. Ephraim lived these lessons Ephraim was an excellent scientist, teacher, and and imparted them to his colleagues and students. His human being. His door was always open. Whenever legacy will endure in the lives of those he touched and in I had a problem or results I did not fully understand, I the greater context of science in Israel. went to him. During our discussions, everything became Jeffrey M. Becker clear. He was also a great lecturer. Three days before he Professor and Head, Microbiology Department passed away, I visited him, and he told me that the most University of Tennessee, Knoxville important thing is to take care of young scientists.

Ephraim was my postdoctoral mentor. I remember him Meir Wilchek Professor of Biological Chemistry as a passionate advocate for basic research who taught Weizmann Institute of Science his students a love of science and a tremendous respect for careful systematic investigation. He always urged us Ephraim achieved the almost unbelievable; while to see the big picture and to pursue important problems. remaining for his entire adult life totally immersed in In that respect, he added greatly to the biochemical science, breathing it 24-7, he managed also to leave sciences in peptide synthesis, enzymology, protein an unforgettable signal imprint on the Israeli society at chemistry, biotechnology, and immunology. He was my large. He did this not only by training scores of students teacher, my supporter, and ultimately, a dear friend. I and and postdocs, many of whom are the backbone of his other students will miss him terribly. Israeli science, but also by serving in key positions on Ephraim emulated the importance of hard work to the national scene. These included the chief scientist scientists. He led a large group of scientists and was of the Ministry of Defense, head of various government also involved in many aspects of Israeli society. These committees, and, ultimately, the President of the State included advocacy for applications of scientific research of Israel. I will particularly remember him for being a very in the industrial sector, and science policy vis-à-vis the wise, highly influential, and broad-minded mentor with a security of Israel and its impact on the economy. Given terrific sense of penetrating humor. his enormous responsibilities, he needed to find a way Yadin Dudai, Professor to provide access to the young scientists that he trained Weizmann Institute of Science into his late 1980s. One way he did this was working literally around the clock. I remember writing papers with Cyril M. Kay is an emeritus professor of Biochemistry at the him through the night, from 1 am to 6 am. How did he University of Alberta, and Howard K. Schachman is a professor do this? He took brief naps to regenerate his strength of Molecular and Cell Biology at the University of California, and then plowed ahead. He was truly a force to behold. Berkeley. Fred Naider Distinguished Professor of Chemistry and References Biochemistry, College of Staten Island 1. Frankel, M., and Katchalski, E. (1942) Poly-condensation of α-Amino Acid Esters. I. Poly-condensation of Glycine Esters. J. Am. Chem. Soc. 64, The City University of New York 2264–2268. 2. Frankel, M., and Katchalski, E. (1942) Poly-condensation of α-Amino Acid Esters. II. Poly-condensation of Alanine Ethyl Ester. J. Am. Chem. Soc. 64, During my last meeting with Ephraim, he was really 2268–2271. 3. Katchalski, E., Grossfeld, I., and Frankel, M. (1947) Poly-Lysine. J. Am. Chem. very tired, but he took my hand, looked in my eyes, and Soc. 69, 2564–2565. 4. Bar-Eli, A., and Katchalski-Katzir, E. (1960) A Water-insoluble Trypsin asked me how will we, at the Weizmann Institute and Derivative and Its Use as a Trypsin Column. Nature 188, 856–857.

ex14 ASBMB Today August 2009 asbmbnews JBC Highlights Computational Biochemistry BY NICK ZAGORSKI

nderstanding how complex bio- but also in drug discovery and Ulogical systems operate requires modeling disease. Thomas Pollard a thorough description of their and Julien Berro’s review provides underlying biochemical mechanisms. a feel for the full range of ways in Until recently, most approaches which mathematical modeling helps toward describing these biochemical us understand actin cytoskeleton- mechanisms have been experimen- dependent cell movement from the tal. Although this has added to our three-dimensional structure of actin understanding of the biochemical monomers to the organization of basis of biological processes, it has actin filaments to how filament struc- also brought a vast and somewhat ture drives movement at the leading disjointed “parts list.” As this list edge of the cell. Jeffrey Kearns and continues to grow and become Alexander Hoffman describe studies increasingly connected, scientific of NF-κB that have been useful in reasoning coupled with experimental developing the concept of cell-state- observation becomes insufficient in providing a detailed dependent rate limiting steps and the role that different understanding of how these systems function. This has isoforms of the same protein play in contributing to led to the recent resurgence of computation as a major complex behavior. tool in studying systems biology. In the fourth minireview, Iyengar and Susana Neves To bring attention to this emerging discipline, the discuss how computational analyses of spatially Journal of Biological Chemistry brought together a series restricted biochemical reactions, such as membrane- of six minireviews this past February that describe some bound receptor binding, have helped identify spatial diverse research areas where computational approaches information as a distinct entity that is transmitted through have provided mechanistic insight into the regulation and cell signaling networks. Avi Ma’ayan introduces the utility function of complex systems. Organized by Ravi Iyengar of graph theory in dealing with and inferring mechanisms and JBC Editor Herbert Tabor, the “Computational Bio- from large data sets; graphs have been successfully chemistry” thematic series, which emphasizes the sys- applied to model complex systems in numerous disci- tems level knowledge that computation provides rather plines, and, similarly, graph-based network analysis has than focusing on computational methods, should open been extremely useful in understanding global regula- the eyes of many JBC authors and readers to the pos- tory features of large biochemical systems. Finally, Jan sibilities of using computational approaches in their own Schellenberger and Bernhard Palsson describe emerg- research. This series will also serve as a great primer ing methods for dynamic studies of metabolic networks for anyone attending the upcoming ASBMB-sponsored based on whole genomes. Although models of meta- small meeting, “Systems Biology for Biochemists,” which bolic networks are themselves not new, this review dis- will be held on October 22––25 in Granlibakken, Lake cusses new approaches that help convert static network Tahoe (http://tinyurl.com/l6e5la, see also the article in maps into dynamic systems, providing a glimpse of how the April 2009 ASBMB Today). the future of computational biochemistry may look. In the first minireview, Jennifer Linderman describes The series is available at www.jbc.org/thematics. how modeling G protein-coupled signaling pathways has been valuable not only in understanding basic mecha- Nick Zagorski is a science writer for ASBMB. He can be nisms of signal transduction such as collision coupling reached at [email protected].

September 2009 ASBMB Today 13 asbmbfirstsecond member words spotlight Liao Garners Marvin Silverman Awarded J. Johnson Award Perkin Medal James C. Liao, Chancellor’s Professor of In recognition of his outstanding work in Chemical & Biomolecular Engineering at applied chemistry, the Society of the University of California, Los Angeles, Chemical Industry 2009 Perkin Medal has has been selected to receive the Marvin J. been awarded to Richard B. Silverman, Johnson Award in Microbial & Biochemical the John Evans Professor of Chemistry at Technology from the Biochemical Northwestern University. Technology Division of the American The Perkin Medal, established in 1906, Chemical Society. The award, sponsored is given annually to a scientist residing by Pfizer, was given to Liao for his work in in America for an “innovation in applied metabolic engineering and systems biology. chemistry resulting in outstanding com- Liao’s research encompasses many areas. He uses metabolic mercial development.” It is considered the highest honor given in engineering and systems biology principles to produce next- the U.S. industrial chemical industry. generation biofuels, and he also develops novel gene-metabolic The medal commemorates the discovery of the first synthetic circuits for use in bioenergy research. Liao is also involved in dye by Sir William Henry Perkin in 1856. The medalist is chosen investigating fat metabolism in hepatocytes and nitric oxide sig- by a jury of officers from the Society of Chemical Industry, the naling in humans and bacteria, as well as intracellular regulation American Chemical Society, the American Institute of Chemical and metabolism. Engineers, and the Chemical Heritage Foundation. Silverman’s research focuses primarily on medicinal chem- Walsh Awarded Inaugural istry: studying the molecular basis of drug action, reaction mechanisms of enzymes, and design and synthesis of pharma- Scott Medal ceutical agents. He has worked to deepen the understanding of Christopher T. Walsh, Hamilton Kuhn several diseases, including epilepsy, cancer, Parkinson disease, Professor of Biological Chemistry & and cerebral palsy. One of Silverman’s many scientific accom- Molecular Pharmacology at Harvard plishments is his synthesis and subsequent investigation of the Medical School, has been awarded the medicinal properties of pregabalin, a γ-aminobutyric acid analog inaugural A. Ian Scott Medal from the that is the active substance in Lyrica, a pain and epilepsy medi- American Chemical Society Texas A&M cation commercialized by Pfizer. Section and Texas A&M University’s Department of Chemistry. The medal recognizes excellence in biological Petsko to Become chemistry research. IUBMB President Walsh received the A. Ian Scott Medal for his contributions to Gregory Petsko, Gyula and Katica Tauber the area of bioorganic chemistry related to natural products. His Professor of Biochemistry & Chemistry at research focuses on biological catalysis and enzymatic reac- Brandeis University, has been elected to tion mechanisms and uses a variety of approaches centered on the office of President Elect of the protein biochemistry to decipher the molecular logic of enzymes. International Union of Biochemistry and Walsh and his colleagues study the enzymatic synthesis of Molecular Biology. Petsko, who is dedicated monomers for the enzymatic assembly lines, the currently the president of ASBMB, will organization and function of the assembly line machinery, and assume the position of IUBMB president enzymes involved in maturation and tailoring steps after release in 3 years at the IUBMB Congress in of nascent products from the assembly lines. Ongoing projects Seville, Spain. include investigating the enzymatic pathway for biosynthesis The IUBMB unites biochemists and molecular biologists in 77 of the vancomycin family of glycopeptide antibiotics; examin- countries through their academies of science, research councils, ing the enzymatic assembly lines that make enterobactin, the or biochemical societies which belong to the IUBMB as either Escherichia coli siderophore, pyochelin from Pseudomonas Adhering Bodies or Associate Adhering Bodies. Its mission is to aeruginosa, vibriobactin from Vibrio cholerae, and yersiniabactin foster and support the growth and advancement of biochemistry from Yersinia pestis; and studying the biogenesis of epothilone and molecular biology as the foundation from which the biomo- (antitumor agent), rifamycin (antitubercular drug), and yersinia- lecular sciences derive their basic ideas and techniques in the bactin to decipher the rules for switching between polyketide service of mankind. synthase and nonribosomal peptide synthetase assembly lines in Current IUBMB President Angelo Azzi commented, “I the synthesis of these proteins. ‘wanted’ Greg to become president for two reasons: I wanted a high caliber scientist and not a retired teacher at the head of the Union and I wanted one from the country where more high qual- ity science is produced.”

14 ASBMB Today September 2009 asbmbfirstsecond member words spotlight Please submit member-related news to [email protected] Sourkes Honored with Eight Members Lifetime Contribution Award Named ACS Fellows Theodore L. Sourkes, professor emeritus Eight ASBMB members were recognized in a ceremony this in the Departments of Psychiatry, past August to honor the first class of 162 American Chemical Biochemistry, and Pharmacology at Society (ACS) Fellows. McGill University in Montreal, has been The ACS Fellows Program was created by the Board of honored with the 2009 Lifetime Directors in December 2008 “to recognize members of the Contribution Award from the International American Chemical Society for outstanding achievements in Society for the History of the and contributions to Science, the Profession, and the Society.” Neurosciences (ISHN). Sourkes received Unlike ACS national awards, the honor of a Fellows designation the award this past June at the annual goes to those who have distinguished themselves in multiple meeting of the ISHN in Charleston, SC. areas, including promoting the science, the profession, and Sourkes is one of the pioneers of Parkinson disease research service to the American Chemical Society. Ultimately, the body in Canada. He demonstrated as early as 1960 that Parkinson of Fellows is intended to reach approximately 1–2 percent of disease involved a deficiency in dopamine. This finding led ACS membership. directly to a clinical trial in which the specific neuropharma- The 162 members “share a common set of accomplish- cological action of l-DOPA (which gives rise to dopamine) in ments, namely true excellence in their contributions to the Parkinson disease was demonstrated. Together with Louis J. chemical enterprise coupled with distinctive service to ACS or Poirier, Sourkes then identified the pathophysiological mecha- to the broader world of chemistry,” said ACS Immediate Past- nism operating in Parkinson disease, which resulted in the president Bruce E. Bursten, who championed creation of the redirection of this research in many laboratories and clinics and program and shepherded it through board approval last year. in disease treatment in general. The fellows come from the entire breadth of ACS’s mem- Since his retirement in 1991, Sourkes has devoted him- bership, including high school teaching, entrepreneurship, self to research on historical topics in biochemistry and government service, and all sectors of industry and academia. neuroscience. Academic chemists make up 72 percent of the new class of fellows, 15 percent are from industry, 7 percent retired nonaca- Taniguchi Receives HUPO demic, 5 percent government, and 1 percent consultants. Distinguished Service Award The following ASBMB members Naoyuki Taniguchi has been selected to were named ACS fellows: receive the HUPO Distinguished Service Award, which will be presented during a James A. Cowan, Professor in the Department of Chemistry special lecture at the HUPO 8th Annual at Ohio State University World Congress in Toronto, Canada in Michael P. Doyle, Professor and Chair of the Department of September. Chemistry and Biochemistry at the University of Maryland Taniguchi graduated from the Catherine Fenselau, Professor in the Department of Chemistry Hokkaido University School of Medicine and Biochemistry at the University of Maryland in 1967 and completed his doctorate F. Peter Guengerich, Harry Pearson Broquist Professor at the Hokkaido University School of of Biochemistry and Director of the Center in Molecular Medicine in 1972. He was then appointed assistant profes- Toxicology at Vanderbilt University sor at the Hokkaido University School of Medicine in 1975. In Bruce E. Maryanoff, Distinguished Research Fellow and Team 1986, he joined the faculty of Osaka University Medical School Leader of the Vascular Research Team at Johnson & Johnson as Professor and Chairman of the Department of Biochemistry, Pharmaceutical R&D where he remains today. His laboratory focuses on glycomics C. Dale Poulter, John A. Widtsoe Distinguished Professor and and proteome research. Chair of Bioorganic Chemistry at the University of Utah Taniguchi served as the chair of HUPO’s Glycomics in Disease Scientific Initiative. In 2005, he was honored by the Harold A. Scheraga, George W. and Grace L. Todd Professor of Chemistry, emeritus in the Baker Laboratory of Chemistry Japanese Government for his contributions to scientific research and Chemical Biology at Cornell University with the Purple Ribbon Medal. Taniguchi is an honorary member of the American Society for Biochemistry and Molecular Biology Elizabeth K. Weisburger, Former Assistant Director for and has served on the editorial board of the Journal of Biological Chemical Carcinogenesis in the Division of Cancer Etiology Chemistry. at the National Cancer Institute

September 2009 ASBMB Today 15 specialinterest Lifting the Veil on Biological Research BY NICK ZAGORSKI

Shapiro, a biochemist and structural biologist at Columbia This article is the first in a series in which University (who Richard Rifkind actually tried to recruit, we look at the intersection of science and unsuccessfully, to Sloan-Kettering when he was chairman). popular culture. Scientifically, the MacGuffin driving Naturally Obsessed is the lab’s quest to solve the crystal structure of AMP- activated protein kinase (AMPK), a critical mediator of f you’re curious to learn more about medicine, anthropol- cellular energy balance. However, the film is really more Iogy, or forensic science, you can turn to television and concerned with the path taken; during the course of an film for an abundance of viewing options—both in the fic- hour, the viewer follows the students and mentor over 3 tion and reality genres—that can serve to educate, inform, years—both inside and out of the lab—as they experience or at least entertain you. Biological research, on the other the camaraderie and competition of science, the joys and hand, is woefully neglected; the inner workings of aca- frustrations of bench work, and the endless tug-of-war demic, medical, or industrial labs where tireless researchers between career and family—issues most anyone involved labor away at the fundamental discoveries that someday in a Ph.D. program can empathize with. will lead to the next medical breakthrough remain veiled in “The original title of our film was actually The Lab,” mystery to many in the general population. notes Carole, “but we decided to change it because we It’s a situation that Richard Rifkind knew all too well; realized during the production that this film was really while working as a professor and laboratory head at Colum- driven by the people and had a great deal of emotional bia University and later as Chairman of the Sloan-Kettering intensity. The Lab would have been just too bland.” Institute, Rifkind was often asked about his work, and he Indeed, through its combination of action footage in could never describe laboratory life in a way that would sat- the lab and sit-down interviews with the lab members, isfy both him and the questioner. So, after he retired from Naturally Obsessed does a wonderful job capturing the active research in 2004, he and his wife Carole, an author and architectural historian, decided to remedy this situ- ation. As both were budding filmmak- ers who were just wrapping up their first project (a documentary about the changing social and demographic landscape of Venice), the pair decided to lift the veil on scientific research through film. Now, over 4 years, hundreds of hours of video footage, five different editors, and about 20 different rough cuts later, the Rifkinds have completed their labor of love: Naturally Obsessed: The Making of a Scientist. The documentary chronicles the lives of three graduate students work- Richard and Carole Rifkind chronicle the lives of three graduate students working in an x-ray crystallography lab in the film, Naturally Obsessed: the Making of a Scientist. ing in the laboratory of Lawrence Photo by Amy Roy.

16 ASBMB Today September 2009 specialinterest

mood and mindset of being a graduate student (and “We live in a society that values science, as well as a young, untenured professor) in the structural biology field, society that depends on science,” Carole says. “But at the including the struggles. As the film points out, structural same time, it’s a society that doesn’t always appreciate or biology remains even today a difficult line of research understand the scientists behind the work. And I hope where success can depend as much on luck and black that our film can help provide some of that appreciation, magic as knowledge and technical skill (a case highlighted and maybe even inspire some other scientist filmmakers. in a very memorable scene in which Shapiro discusses After all, I think we’ve shown that laboratory research can tongue-in-cheek how playing the Flaming Lips song be tense, dramatic, and even have a happy ending—all the “Yoshimi Battles the Pink Robots” while mounting crystals stuff of Hollywood.” increases the probability of diffraction). Interested in seeing Naturally Obsessed?Visit ASBMB. This degree of scientific uncertainty was one of the org on September 15 at 2:00 pm, when we will present Rifkinds’ biggest concerns when they began shooting their an online screening of this acclaimed film. Also, check film. “We worried whether we would have to change the out our podcast interview with Lawrence Shapiro at direction of our story in a year or so depending on the www.asbmb.org/Interactive.aspx. results, or even if we would have a story to tell,” Richard says. “In many ways, our documentary, or any creative Nick Zagorski is a science writer at ASBMB. He can be reached endeavor for that matter, is very similar to a scientific at [email protected]. experiment, and that’s how we decided to view this project going in. Fortunately, for both us and the lab, the experi- ment turned out well.” Meeting Award Lectures A similar concern arose once the film was complete; Richard worried that the frustrations and failures por- ASBMB will be screening our 2009 annual meeting award lectures in addition to Naturally Obsessed; if you missed the trayed in the film might deter some viewers from consid- meeting or a particular talk, you can come back and check it ering a career in science, because in addition to providing out. The full ASBMB screening schedule is as follows*: more transparency about academic research, the film October 15: could serve as a motivational tool for young people. And David R. Davies, “Fifty Years of Protein Structure: From though some people expressed concerns over the grueling Myoglobin to the Innate Immune System.” (Herbert Tabor/ hours and risks of failure, Richard says that in the various Journal of Biological Chemistry Lectureship) screenings he and Carole have attended, the reception has November 11: been extremely positive. “Students would come up to us Sandra L. Schmid, “Clathrin-mediated Endocytosis: after screenings and tell us they loved the film’s realism Dynamics and Dynamin.” (William C. Rose Award) and are thankful that they now knew what to expect when December 15: they go to graduate school,” he says. And though Naturally Sarah Spiegel, “The Outs and the Ins of the Pleiotropic Obsessed was meant primarily for the general public, the Lipid Mediator Sphingosine-1-phosphate.” (Avanti Award in Rifkinds were also pleasantly surprised by the stamp of Lipids) approval scientists have been giving the film in regards to January 15: its depiction of laboratory life. Phillip D. Zamore, “What Fruit Flies Teach Us About RNA Silencing.” (Schering-Plough Research Institute Award) Since the film’s debut this past March at the Environ- mental Film Festival in Washington, D.C., the Rifkinds FEBRUARY 15: Susan L. Lindquist, “Prion Proteins: One Surprise After have been keeping busy showing their documentary across Another.” (FASEB Excellence in Science Award) the country, a process they enjoy a great deal. “It’s so much March 15: fun interacting with all kinds of individuals and building a Rochelle D. Schwartz-Bloom, “Science Education: A dialogue with the audience,” she says. Carole adds that she Basic Scientist’s View of Translational Medicine.” (ASBMB and Richard are also preparing the DVD of the film, which Award for Exemplary Contributions to Education) will include bonus tracks such as extended interview *The current lineup is tentative and may be subject to segments—“they were really fascinating but did hinder the change; please check back at ASBMB.org to find updates flow of the movie somewhat,” Carole says—and highlights on days and times. from some of the audience screenings.

September 2009 ASBMB Today 17 sciencefocus Mildred Cohn: Isotopic and Spectroscopic Trailblazer BY NICK ZAGORSKI

ildred Cohn’s scientific career could Mperhaps be described as a series of silver linings. She displayed tremen- dous intellectual talent in her early years, completing her undergraduate degree in chemistry at Hunter College before the age of 18, designing a model of a combustion engine by 21, and obtain- ing a Ph.D. under legendary chemist and Nobel laureate Harold Urey by 24. These achievements would make her the pick of the scientific litter today. However, back in Cohn’s day, even her own Ph.D. advi- sor could not help her find a suitable job, for in the era before equal opportunity employment, Cohn had two strikes going against her that no amount of talent could seem to overcome: being a woman and being Jewish. And so Cohn’s career advancement was met with one obstacle after another, whether it was being unable to enroll in Columbia University’s male-only graduate program in chemical engineering or the fact that it took her 21 years after earning her Ph.D. to receive her first tenure-track faculty appointment. Yet despite many of these setbacks, Cohn received opportuni- ties; her foray into Urey’s lab that followed her denied entry into chemical engineer- ing sent her down a path where she could Mildred Cohn in her lab at the University of Pennsylvania, shortly after her arrival. combine her loves of physics and chem- istry and placed her in the forefront of the emerging field of biochemistry, while her long period Together, those silver linings have made Cohn one as a research associate educated her in diverse areas of of the leaders in applying physical chemistry to tackle biochemistry and eventually allowed her the freedom to biological questions. She pioneered the use of stable iso- pursue challenging projects without worrying about pub- tope tracers to study enzymatic reactions and metabolic lishing results. processes, particularly related to organic phosphates and

18 ASBMB Today September 2009 sciencefocus

ATP. Later, she addressed the same topics with electron Master’s in chemistry but then had to leave and try to find spin and nuclear magnetic resonance, becoming one of the a job. This was no small feat, considering the U.S. was still first researchers to use these technologies in biochemistry reeling in the Depression, but soon Cohn found a posi- as well. “I was definitely a rare bird back then,” she says tion at the National Advisory Committee for Aeronautics jokingly. Of course, no mention of Mildred Cohn and (NACA, which eventually became NASA) laboratory in the word “first” would be complete without recognizing Langley Field. There, as one woman amongst 70 men, that she was the first woman appointed to the Journal of Cohn worked on a project trying to develop improved Biological Chemistry Editorial Board and the first female fuel-injection airplane engines, an initially rewarding president of ASBMB. experience that taught Cohn the value of applied science but one that ultimately fizzled; within 2 years, she had Ready for Takeoff reached a dead-end in her position. However, she had While the distinction of being a Jewish woman would saved enough money to return to Columbia and partially prove a thorn during Cohn’s scientific career, growing up finance her graduate studies. as the daughter of a pair of Russian Jewish immigrants in New York City during the 1920s was initially a benefit; Tracing a Path to Independence both of her parents had strong rabbinical backgrounds For financial reasons, Cohn’s first plan was to continue and thus valued scholarly pursuit. In fact, Cohn’s father some of her NACA work and study fuel vaporization for indoctrinated in her that she could achieve great success if her Ph.D. thesis, combining course work at Columbia she put her mind to it—an with experimental work at uncommon attitude of the NACA. The chairman fathers towards daughters …no mention of Mildred of the chemical engineering at that time. That led her Cohn and the word ‘first’ department quickly quashed to excel in chemistry and “ would be complete without that idea. So Cohn fell on a math, though surprisingly, backup plan and asked Urey, she didn’t particularly care recognizing that she was who had taught some of her for biology. “Of course, Master’s courses, about joining when I went to high the first woman appointed his group. Initially hesitant, school, biology was pri- to the Journal of Biological Urey soon agreed, and Cohn marily a descriptive field; was quickly introduced to the all we did in biology class Chemistry Editorial Board world of stable isotopes and was dissect frogs,” Cohn and the first female their many applications. After says, noting that she grew president of ASBMB. failing in her first project of to appreciate the beauty trying to separate carbons of biology as it began to 12 and 13, she focused her intertwine with the progression of her career. efforts in a more productive area of studying the rates Her first significant setback occurred at Hunter College, of exchange of” oxygen 18-containing water and organic which she started attending at the age of 14, when she compounds. realized she could not pursue a major in physics; “it wasn’t By the end of the 1937 academic year, Cohn was ready offered as a major, probably because it was assumed that to graduate, though her future remained uncertain; jobs girls shouldn’t or didn’t want to be physicists,” Cohn says were still scarce, and the few openings available at the (Hunter was an all-girls college back then). She notes that, major chemical companies were effectively restricted in fact, many of her science teachers were uninspiring (an to white males. Fortunately Vincent du Vigneaud, then engrossing senior-year course in physical chemistry was a a researcher at George Washington University, was notable exception), and she progressed primarily through interested in introducing stable isotope tracers into his her own persistence and desire to learn. metabolic studies of sulfur amino acids, and so David After completing college in 1931, Cohn attended Rittenberg and Rudolf Schoenheimer, close colleagues of Columbia for 1 year, paying her way with savings from Urey, convinced du Vigneaud that Cohn would be an ideal previous summer jobs and babysitting; she obtained a person to join his lab as a postdoc. And in another sign of

September 2009 ASBMB Today 19 sciencefocus continued …every member in the chemistry “ faculty personally congratulated me when I got the position with du Vigneaud, because obtaining an academic position, even a lowly postdoc, was such a rare achievement, particularly for a woman.

the times, Cohn notes that “every ”member in the chem- istry faculty personally congratulated me when I got the position with du Vigneaud, because obtaining an aca- demic position, even as a lowly postdoc, was such a rare achievement, particularly for a woman.” Mildred Cohn at her 96th birthday party. Over the next several years, Cohn worked on a variety of questions involving methionine and cysteine metabo- lism; with deuterium labels, she helped establish that methi- physicist; maybe we could find him a job too.” onine was the source of the methyl groups in both choline After spending so many years trying to escape the clas- and creatine and she also elucidated the mechanism behind sification of being a second-class citizen due to her gender the conversion of methionine to cysteine in rats. The work and religion, this letter was priceless. “I remember show- was very exciting, but eventually Cohn tired of the appren- ing the letter to Gerty [Cori], and she said, ‘Mildred, frame ticeship role as male postdocs in the group came and went it; I never got a letter like that.’” However, even though her on to higher positions. “I didn’t even care about advancing husband was extremely supportive and offered to move to in rank,” says Cohn. “I just wanted the freedom to pursue Baltimore, Cohn turned the offer down for two reasons: my own interests and goals, but even after 9 years, that free- the position was a service job, and she sensed that Cori’s dom was limited in du Vigneaud’s lab.” lab would be a special place. In 1946, though, an opportunity arrived when Cohn’s Her intuition proved correct, and it wasn’t just because husband, theoretical physicist Henry Primakoff, received a the Coris won the Nobel Prize for Medicine in 1947 (inci- job offer from Washington University in St. Louis; Wash- dentally becoming the third straight Nobel laureate Cohn ington was one of the few schools that had only partial would train with­—du Vigneaud would win for Chemistry nepotism rules, and it enabled Cohn to obtain a research in 1955). At Washington University, Cohn had found a associate position with Carl Cori in the biochemistry second mentor and shining example of female success in department. science in Gerty Cori—“she sort of adopted me as soon as I got to the lab,” Cohn says. Cohn notes that she initially A Resonating Career published two collaborative papers, one with each Cori, A short while after Cohn had arrived at Washington but then conducted her own research the rest of the way, University, she received a most interesting piece of mail; long before she finally received a long-overdue professor- it was a letter from the Johns Hopkins University offer- ship in 1958. ing her a job. She particularly enjoyed the closing part of Cohn’s hope was to expand isotope studies—not simply the offer, which stated, “we understand your husband is a to use them as metabolic pathway tracers, but as tools

20 ASBMB Today September 2009 sciencefocus continued

to gain insight into the mechanisms of enzyme activity, the American Chemical Society’s Garvan Medal and the such as using oxygen-18 to determine bond cleavage in National Medal of Science, among other honors, but the phosphate reactions. She revealed many details about the Women’s Hall of Fame is the first organization not specifi- nature of enzymes with organic phosphate substrates, cally involved in science to recognize her achievements, including discovering that oxidative phosphorylation was which she embraces with some fondness. mechanistically different than glycolytic phosphorylation. “And when I saw that Hilary Clinton and Oprah Win- Further efforts to deduce the detailed phosphate-water frey were also members,” Cohn adds, “I decided this could exchange reactions behind the formation of ATP in oxida- be a good place for me.” tive phosphorylation proved intractable though (this was If you are interested in learning more about Mildred Cohn’s before Peter Mitchell developed his chemiosmotic hypoth- research, read her JBC Reflection comparing research life in the esis), so Cohn decided to move into another area. 1930s and 1940s to that of today (http://tinyurl.com/ksf2yy) That area would be analyzing the reactions that used or watch her JBC Centennial video on the ASBMB web site ATP as a substrate and particularly their requirements for (www.asbmb.org/video.aspx). divalent metal ions. She took up new technologies, first electron paramagnetic resonance (EPR) of manganese Nick Zagorski is a science writer at ASBMB. He can be complexes and later nuclear magnetic resonance (NMR) contacted at [email protected]. and produced one of her most memorable experiments, a seminal study demonstrating the effects of metal ions on References du Vigneaud, V., Cohn, M., Chandler, J. P., Schenck, J. R., and Simmonds, S. the 31P spectrum of ATP—particularly memorable for (1941) The Utilization of the Methyl Group of Methionine in the Biological Synthesis of Choline and Creatine. J. Biol. Chem. 140, 625–641. her because the paper was initially rejected by the Journal du Vigneaud, V., Kilmer, G. W., Rachele, J. R., and Cohn, M. (1944) On the of the American Chemical Society but has since become a Mechanism of the Conversion In Vivo of Methionine to Cystine. J. Biol. Chem. 155, 645–651. Current Contents Citation Classic and a JBC Classic fol- Cohn, M. (1953) A Study of Oxidative Phosphorylation with O18-labeled Inorganic lowing its publication in 1962. Phosphate. J. Biol. Chem. 201, 735–750. Cohn, M., and Hughes, T. R. (1962) Nuclear Magnetic Resonance Spectra of Adenosine Di- and Triphosphate II. Effect of Complexing with Divalent Metal A Chapter Finished, a New One Begun Ions. J. Biol. Chem. 237, 176–81. Cohn, M., and Hu, A. (1978) Isotopic (18O) Shift in 31P Nuclear Magnetic Resonance Applied to a Study of Enzyme-catalyzed Phosphate-Phosphate In 1960, Cohn followed her husband after he received a Exchange and Phosphate (oxygen)-Water Exchange Reactions. Proc. Natl. position at the University of Pennsylvania, and though this Acad. Sci. U.S.A. 75, 200–3. move was not of her choosing, it ended up being a tremen- dous boon. Taking a position at the Johnson Foundation, Cohn was now in the same department as Britton Chance, Commander-in-Chief who was also interested in the EPR and NMR techniques that Cohn had initiated at Washington University. Much Considering her own long uphill battle in advancing her like a kid in a candy store, Cohn and her lab had access to scientific career, one might think Mildred Cohn would have some of the finest instruments and expertise in magnetic found a great platform to advance women’s issues when resonance, and over the next two decades, she used them she became the first female ASBMB president in 1978. to look at numerous enzyme-substrate complexes like cre- However, she decided to take a gender-neutral approach to atine kinase, pyruvate kinase, and adenylate cyclase. the presidency and not carry any specific agenda, although Though Cohn closed down her laboratory about 10 years ago, she still maintains an office at the university she still managed to distinguish herself from her male where she occasionally advises graduate students or predecessors in an unusual fashion. “One of the duties postdocs and remains active in a number of organiza- of president was to preside over a business meeting at tions, including the Chemical Heritage Foundation and each year’s conference, and I remember after mine, one the American Philosophical Society. And, while reflecting of my colleagues came up to me and complimented my back on her unusual career is nothing new to her—she’s efficiency,” she says. “He told me that the members were written several reflections for journals and has recently so used to presidents rambling on and on that they often completed a 500-page memoir that she will present to her family—she’s not finished looking ahead either. This wandered in late, but today, he wandered in, and the meet- October, Cohn will be formally inducted into the National ing was already over; apparently, the meeting I presided Women’s Hall of Fame in Seneca Falls, New York. Acco- over was the shortest on record.” lades are not foreign to Cohn, who has received both

September 2009 ASBMB Today 21 asbmb history The ASBMB Annual Meeting* BY RALPH A. BRADSHAW, Society Historian

he recent ASBMB annual meeting in New Orleans The First Meeting Twas an important milestone for the Society because The society’s first meeting was held in Washington, D.C., it was the 100th in the series of annual meetings that have at the downtown campus of George Washington Univer- been occurring since 1907. (The 3-year gap between this sity on May 8 and 9, 1907 (Fig. 1), just over 4 months after centennial celebration and that of the Society was caused the Society was formed. The meeting was attended by 26 by a period during World War II (1943–1945) when no of the 81 charter members. meetings were held.) The decision to hold the first meeting so soon after The annual meeting has always been an integral part of the formation of the Society resulted from a mail ballot the Society’s activities. Indeed, one of the main reasons for to the members of the Society’s council. In it, William forming a separate society in 1906 had been the perceived J. Gies, the Society’s first secretary, argued that it would problems of accommodating the growing number of provide an opportunity to consider the new constitution biochemical research papers in the American Physiologi- and “enable… a prompt beginning of the scientific career cal Society’s (APS) annual meeting, which, prior to the of the society.” (As it turned out, the new constitution was formation of the American Society of Biological Chemists not considered until the second annual meeting, held in (now ASBMB), had been the principal forum for their December 1907/January 1908.) presentation. The time and place for the meeting were selected to allow attendees to also take part in the Congress of Ameri- can Physicians and Surgeons, the meeting of the Wash- ington section of the American Chemical Society, and the APS annual meeting. The ASBC meeting had four sessions spanning two days. Two sessions were held jointly, one with APS and one with the American Chemical Society (ACS). A total of 43 papers were read, mostly by charter members of the Society, and the abstracts were published in a special section of Volume 3 of the Journal of Biological Chemistry (JBC), titled Proceedings of the American Society of Biological Chemists. This addendum to the journal, which sup- plied meeting abstracts and information of general interest to Society mem- bers, including recommendations on various aspects of nomenclature and Council delib- erations, contin- ued into the early 1940’s when it was replaced by the Fed- Fig. 1. The front and back of the program eration Proceedings. for the Society’s first annual meeting.

22 ASBMB Today September 2009 asbmb history

It is interesting to note that on the back of the pro- American Bacteriolo- gram (Fig. 1) there is an invitation to a reception at the gists (now the American White House for the attendees and guests of the meeting. Society for Microbiology) This reflects a more open access to high U.S. government in addition to the APS officials in those days, in particular those of the Theodore and the ACS. This policy Roosevelt administration. not only reflects the broad Holding an annual meeting in conjunction with those interests that were (and of other scientific societies would become a hallmark of still are) commonly held by ASBC/ASBMB. In the earliest days, meetings were held many ASBMB members, with various sections of the American Association for but it also underscores the the Advancement of Science (AAAS) and the Society of central role that biochem- istry plays in all biological sciences. After the Federa- tion of American Societies for Experimental Biology (FASEB) was founded in Fig. 3. Howard Hiatt, Jerard Hurwitz, and Herbert Tabor December 1912, the Soci- at an Atlantic City meeting. ety met regularly as part of this group for the next 60 years. However, in the period from 1971 to 2005, only some of the Society’s meetings were held with FASEB; other joint meetings were held with societies not affiliated with FASEB. In 2005, after a thirty- year hiatus, the ASBMB began meeting with FASEB again on a regular basis and continues to do so today (Fig. 2.).

Meeting Places The Society’s meetings prior to WWII were relatively small and generally took place in the eastern United States (and Canada) at academic institutions. In 1946, at the first meeting to be held after a 3-year wartime hiatus, attendance was large enough to warrant using a conven- tion center. This meeting was held in Atlantic City, NJ and began a 30-year period during which this was the favored venue. Between 1946 and 1975, the Society met in Atlan- tic City 18 times, all as part of the larger FASEB meeting. (Chicago was the next most popular site, and the Federa- tion met there six times during the same period.) Thus, for several generations of biochemists, Atlantic City, which was also the location of the Society’s 50th Anniversary Golden Jubilee in 1956, was synonymous with ASBMB (and FASEB) meetings, and many still fondly recall impor- tant discussions and exchanges on the boardwalk (Fig. 3). It took nearly 50 years for the Society to move the annual meeting beyond sites in the East and Midwest. The first meeting west of the Mississippi (discounting St. Louis) was in 1955 when the ASBC met in San Francisco for the first time. This was the th46 annual meeting. The Fig 2. The 2009 ASBMB Annual Meeting Guide. eastern dominance of annual meetings would continue

September 2009 ASBMB Today 23 asbmb history continued the latest research findings shared, but the “dealings” of the biological research com- munity were accomplished as well. The Federation meeting was so significant to all the member societies that every- one, from upper level graduate students to the most senior investigators, attended faith- fully. This would continue to be true well into the 1970s.

A Break from FASEB An occurrence not related to science eventually altered the pattern of the Society holding its meeting with the Federation. In reaction to the antiwar demonstrations during the 1968 Democratic convention in Chicago and the city’s responses to them, the Council received letters and petitions signed by over 400 members objecting to the FASEB meeting scheduled for Chicago in 1971. The situation was exacerbated by the fact that the Council was already unhappy with the Society’s relationship with FASEB. A Fig. 4. Exhibit booths as the 1966 (top) and 2006 (bottom) FASEB meetings. poll of the membership was conducted, and although no until the early 1980s, when the annual meetings began to clear majority opinion on the question was obtained, the take place in alternating West Coast, Midwest, and East Council subsequently decided to meet separately from Coast cities. FASEB in San Francisco in June 1971 for the first time It is important to note that the Society’s annual meet- since 1912. In 1972, the Society met with FASEB again, but ing, particularly in the first 75 years, had a similar atmo- a pattern of meeting separately from FASEB on occasion sphere to a reunion, as it was a meeting place of old was established and continued for another 3 decades. friends who otherwise saw each other infrequently. It was also a place for young people to make new friends and The Winds of Change acquaintances, known in today’s parlance as “network- Although the primary purpose of the annual meeting is ing.” It should be remembered that cross-country travel scientific communication, exhibitions by vendors of services prior to jet transportation was slow and infrequent. As a and commodities important to researchers have always been result, there were fewer competing meetings. Add to this a major part of the event (Fig. 4). Not only did this longstand- the absence of facile electronic communication such as ing arrangement provide opportunities for meeting attendees fax, email, and teleconferencing, and it is easy to see why and companies to exchange information about the availability the social content of the meeting was vital. The informal of new reagents and equipment, it also helped underwrite the science discussions held outside the formal presentations cost of the meeting and provided income to support other made attendance of paramount importance. Not only were Society activities.

24 ASBMB Today September 2009 asbmb history continued However, by the mid-1980s, the Society began to look popular venues for meetings. The city demanded guar- at the net meeting income resulting from the cyclical antees of 1,800 hotel rooms sold before the convention separate meeting format (two “stand-alone” meetings out center could be rented. As the size of the national meeting of every three) and realized that significant changes were shrank, this guarantee became impossible to fill. Thus, by occurring. First and foremost, there was a decline in atten- the mid-1990s, the Society was forced to reevaluate its dance. While this was likely due to a number of factors, meeting philosophy and to begin making decisions on the predominant one was competition. The Society was, to when and where to meet on a year-to-year basis. a degree, a victim of its own success. As biochemistry rap- It should be noted that FASEB’s meeting strategy was idly expanded into what is commonly called “molecular also changed in 1993. Because the number of FASEB biology,” there was a concomitant rapid expansion of all societies had been rapidly increasing since 1990 and many of the biological sciences of the newer member in general. New societies societies met separately, formed in areas that were …the Society’s annual the “FASEB Meeting” was traditionally part of bio- now a misnomer. A new chemistry, and there was a meeting, particularly in the meeting called “Experi- proliferation of meetings, “ first 75 years, had a similar mental Biology” was both large and small, some atmosphere to a reunion. created to replace the old associated with new soci- one, and societies were eties and some with other free to meet as much or as non-profit organizations. (FASEB itself started a series of little within the Experimental Biology umbrella as served very successful smaller meetings around this time.) The their own needs. Because” plans for the Experimental resulting effect on the Society’s annual meeting was dra- Biology meeting had to be made about 4 years before the matic; by the 1990s, it had decreased considerably in size actual meeting, the ASBMB Council had to forecast par- from the first stand-alone meeting in 1971. ticipation well ahead of time. Finally, in 2002, a decision Exhibitors were, of course, looking at the number was made to meet with Experimental Biology every year of attendees at a particular meeting compared with the beginning in 2005. This strategy provided a more or less costs of booth rental, shipment of equipment and materi- steady revenue stream that did not depend on the vagaries als, and the salaries of employees necessary to staff the of attendance and exhibit booth rental. In addition, the booths. Although attending both the FASEB meeting and logistics of the meeting were left to the meeting manage- the ASBC/ASBMB meeting had been an annoyance to the ment specialists of FASEB, so that the Society would only exhibitors, they realized that the ASBC/ASBMB meetings have to worry about scientific content. were the best way to reach biochemists and molecular Thus, in 2009, at the 100th anniversary of the annual biologists. But, by the early 1990s, with the decrease in meeting, the ASBMB has returned to meeting with other attendance and the fact that many of the exhibitors were FASEB societies, including some of its original 1912 having financial problems due to a downturn in the gen- partners. Although this has proven to be a very workable eral economy and several mergers within the biomedical arrangement for the past several years, it is, of course, equipment industry, the ASBMB annual meeting became not known whether this will remain the case. As yet less attractive. This, in turn, affected the number of booths unforeseen changes in science may force new formats and they rented and hence the bottom line of meeting revenue. arrangements in the annual meeting and bring about new The resultant decline in registration income, combined changes. with a reduction in booth rentals by exhibitors, led to decreased net income from the annual meetings. Because Ralph A. Bradshaw is a professor of chemistry and pharmaceutical meeting locations had to be contracted several years in chemistry and deputy director of the NCRR Mass Spectrometry advance, the Council was increasingly forced to make Facility at the University of California, San Francisco. He is also the hard decisions on which societies to meet with and where ASBMB Society Historian and can be reached at [email protected]. to meet. Complicating this situation was the fact that cities began demanding minimum attendance numbers *This article is part of a series based on the book, “The at the meeting (evaluated by the numbers of hotel rooms ASBMB Centennial History: 100 Years of the Chemistry rented by attendees) before they would rent the conven- of Life.” by R.A. Bradshaw, C. C. Hancock, and N. Kresge. tion centers that were vital for exhibit and meeting space. To learn more about ASBMB’s history or to order the book, An example was San Francisco, which was one of the most go to www.asbmb.org/history.

September 2009 ASBMB Today 25 2010 annual meeting The Chemistry of Life BY PETER J. TONGE AND ADRIAN WHITTY

hemical biology involves the use of chemical perspec- genase (IMPDH) from the protozoan Ctives and techniques to explore biological processes, parasite Cryptosporidium parvum whereas drug discovery constitutes the direct application of and is using mechanistic differences

designed, discovered, or engineered molecules to achieve between the protozoan and human Tonge specific perturbations in human biology. The Annual Meet- enzymes to develop specific inhibi- ing theme “Chemical Biology and Drug Discovery” thus tors. Jessie M. English (Merck & Co., encompasses a very broad range of science. Rather than Inc.) will discuss the growing impor- attempting to cover this vast area evenly—and therefore, tance of polypharmacology in drug by necessity, superficially—we instead identified as ses- discovery and highlight both the sion topics four specific subjects that benefits and represent areas of rapid progress that drawbacks of we believe will be of interest to a broad Rather than compounds cross-section of the field. These topics “attempting to that inhibit WHitty are “Mechanisms of Drug Action,” multiple “Dissecting Cellular Processes,” “Drug cover this vast kinases. Peter J. Tonge (Stony Brook Resistance,” and “Evolution, Engineer- University) is developing compounds ing, and Design.” Although two of the area evenly... that target fatty acid and menaqui- sessions are nominally designated as we instead none biosynthesis in pathogens “Drug Discovery,” and the other two such as Mycobacterium tuberculosis, are called “Chemical Biology,” they are identified as Francisella tularensis, and Staphylo- to a significant extent complementary session topics coccus aureus and will the discuss the and, in all cases, give a molecular and importance of designing slow-onset mechanistic perspective on the prob- four specific enzyme inhibitors that have long lems discussed. residence times on the target. Our speakers include representa- subjects that Session 2, “Dissecting Cellular tives from both industry and aca- represent Processes,” includes three distinct demia, due to their common interest perspectives on the development in the theme, which allows us to areas of rapid of chemical and biochemical tools include problems and examples from for probing cellular processes. Tom the most fundamental to the directly progress that Wandless (Stanford University) applied. After each talk, we aim to we believe will will illustrate his group’s work on actively foster open and substantive engineering conditional protein discussion of the issues raised by each be of interest to stability and using it to interrogate presentation, with the goal that par- a broad cross- biological function in cultured cells ticipants will leave with an enriched as well as organisms ranging from understanding of the current chal- section of the yeast and Apicomplexan parasites to lenges and opportunities in the field. mice. Joanna S. Fowler (Brookhaven Details of the sessions, speakers, and field. National Laboratory) will describe topics are as follows. ” the development and application of Session 1, titled “Mechanisms of Drug Action,” focuses radiotracers labeled with short-lived positron emitters and on methods to determine the molecular basis for drug their application to problems in neuroscience including action and how this information is exploited to develop and drug addiction. Adrian Whitty (Metcalf Center for Sci- optimize lead compounds. Lizbeth Hedstrom (Brandeis ence and Engineering) will discuss the activation mecha- University) is targeting inosine monophosphate dehydro- nism of the RET tyrosine kinase receptor and how the

26 ASBMB Today September 2009 molecular interactions involved correlate with functional Hilvert (Swiss Federal Institute of Technology) will dis- outcomes at the cellular level. cuss engineering of enzymes and what it reveals about the Session 3, “Drug Resistance,” addresses this important complex interplay between structure, stability, and function problem using examples from antibacterial, antiviral, in these delicately balanced and highly optimized molecules. and anticancer drugs, encompassing both the molecular Frances H. Arnold (California Institute of Technology) will mechanisms responsible for drug resistance as well as the depict how directed evolution can be used to generate highly current thinking on approaches to avoid or circumvent efficient new biocatalysts and what those studies have taught drug resistance. John Blanchard (Albert Einstein College us about natural protein evolution and the complex interplay of Medicine of Yeshiva University) will explain the mecha- between protein sequence, structure, and function. Alexey nisms of drug resistance in tuberculosis chemotherapy. Lugovskoy (Biogen Idec, Inc.) will describe the application Celia Schiffer (University of Massachusetts-Amherst) will of protein engineering to developing protein drugs with describe the “substrate envelope hypothesis” and its use in improved properties, which will be illustrated with specific designing inhibitors of HIV protease that avoid resistance examples of drugs that are currently in development. mutations. Joseph Wu (Pfizer, Inc.) will present recent work In addition to the presentations by the invited speakers, on mechanisms of drug resistance involving mutations in 12 short talks will be chosen from the submitted abstracts to cKit in gastrointestinal cancer patients. allow for the presentation of new and exciting results. The final session, “Evolution, Engineering, and Design,” aims to explore recent progress and current thinking on Peter J. Tonge is a professor in the Department of how directed evolution of proteins and organisms can Chemistry at Stony Brook University and can be contacted be exploited to achieve desired functional outcomes, the at [email protected]. Adrian Whitty is an associate engineering principles that relate protein structure to protein professor in the Department of Chemistry of Boston University function, and how these principles are being applied to at Metcalf Center for Science and Engineering and can be engineer proteins for therapeutic use in humans. Donald contacted at [email protected].

Chemical Biology Symposium: Drug Resistance and Drug Discovery Drug Resistance Mechanisms in Mycobacterium Symposium: tuberculosis, John Blanchard, Albert Einstein College of Mechanisms of Drug Action Medicine of Yeshiva University Kinase Inhibitor Specificity and Targeting Human Combating Drug Resistance: The Balance Between Disease, Jessie M. English, Merck & Co, Inc. Inhibition and Substrate Recognition, Celia Schiffer, University of Massachusetts-Amherst Targeting a Prokaryotic Enzyme in a Eukaryotic Pathogen, Lizbeth Hedstrom, Brandeis University Molecular Mechanisms of Resistance to Imatinib or Sunitinib in KIT Mutants from Patients with Slow-onset Enzyme Inhibition, Residence Time, Gastrointestinal Stromal Tumors, Joseph Wu, and in Vivo Drug Activity, Peter J. Tonge, Stony Brook Pfizer, Inc. University Symposium: Symposium: Chemical Biology: Chemical Biology: Evolution, Engineering, and Design Dissecting Cellular Processes How Proteins Adapt: Lessons from Directed Imaging Brain Chemistry in Diseases of Addiction, Evolution, Frances H. Arnold, California Institute of Joanna S. Fowler, Brookhaven National Laboratory Technology General Methods to Conditionally Regulate Teaching Old Enzymes New Tricks, Donald Hilvert, Protein Function, Tom Wandless, Stanford University Swiss Federal Institute of Technology Towards an Integrated View of Receptor Signaling, Engineering of Monovalent, Multivalent, and Adrian Whitty, Metcalf Center for Science and Bispecific Antibodies for New Therapeutic Engineering Applications, Alexey Lugovskoy, Biogen Idec, Inc.

September 2009 ASBMB Today 27 2010 annual meeting continued New Frontiers in Genomics and Proteomics BY DAVID N. ARNOSTI AND MICHAEL WASHBURN

odern biochemistry and molecular biology com- cellular systems. Post-translational Mmonly call on many tools to generate novel biologi- modifications of histones, for exam- Arnosti cal insights and new hypotheses. Genomics and proteom- ple, are critical regulatory modifica- ics technologies have often been thought of as discovery tions that define the transcription driven and high throughput approaches. Over the past state of chromatin and DNA. All the several years, however, this has changed. Genomics and presenters in this symposium are proteomics tools are being increasingly used by a wider developing and applying exciting new variety of biological researchers. These applications will proteomics tools for the analysis of be the subject of the 2010 ASBMB meeting theme, “New post-translational modifications. For- Frontiers in Genomics and Quantitative Proteomics.” rest M. White (Massachusetts Insti- Washburn The first proteomics symposium, “Quantitative Pro- tute of Technology) and his group teomic Analysis of Protein Complexes,” is designed to focus on the quantitative analysis of highlight how protein mass spectrometry can be used protein phosphorylation events in signal transduction in a quantitative fashion to provide new insights into cascades. They have analyzed the epidermal growth factor multi-protein complexes. Up until recently, there have reception signaling networks and T cell signaling using been few tools available to study these dynamic molecular advanced proteomics tools. Yingming Zhao (University of machines in a systematic and quantitative way. Lan Huang Chicago) and his group have characterized novel histone (University of California, Irvine) will describe her studies modifications like lysine propionlyation and butylation. on the dynamics of the proteasome. This critical molecu- They have also used proteomics approaches to character- lar machine is involved in the regulation of a variety of ize the widespread nature of lysine acetylation in cells, processes, the most widely studied being the degrada- revealing that this modification is more common than tion of ubiquitinylated proteins. Major questions remain previously thought. Joshua J. Coon (University of Wiscon- regarding how the proteasome itself is regulated and how sin, Madison) has been a leader in the development of a it changes with cellular states and stimuli. Lan Huang and novel protein mass spectrometry system named “electron her colleagues are taking an innovative approach to begin transfer dissociation” that has excellent capabilities for the to address these questions. Michael Washburn (Stow- analysis of long portions of proteins. This technology has ers Institute for Medical Research) has been developing particular application in the analysis of histone tails and straightforward quantitative proteomics tools for quan- phosphorylation patterns. titative analysis of multiprotein complexes and protein The first genomics symposium, “Model Organisms and interaction networks. He will talk about how his group New Frontiers I,” will feature speakers who have contrib- uses these tools to analyze transcriptional regulatory com- uted significant insights on mechanisms of gene expres- plexes and characterize new interactions of well known sion in vertebrates, the role of microbial communities in complexes like RNA Polymerase II. Carol V. Robinson human health, and the diversity of microbial microbiomes (University of Cambridge) will explain a new area of mass that are resistant to conventional methods of characteriza- spectrometry that analyzes whole protein complexes. Rob- tion. Nearly three decades ago, transcriptional enhancers inson has published ground breaking mass spectrometry- were characterized as small viral regulatory segments that based structural studies on the COP9 signalsome and the drove gene expression in a distance- and orientation-inde- translation factor eiF3. pendent fashion. Over the years, the roles of these tran- The second proteomics symposium, “Quantitative scriptional control elements in development and disease Analysis of Post Translational Modifications,” is designed have been intensively explored, but fundamental ques- to highlight the exciting applications of new protein mass tions remain. Using comparative genomics and molecular spectrometry techniques for the analysis of post-transla- genetics, Edward M. Rubin (U.S. Department of Energy tional modifications. These modifications play important Joint Genome Institute) has tackled some of the most roles in the regulation of proteins, protein complexes, and enigmatic of these elements—ultraconserved sequences

28 ASBMB Today September 2009 that show little variation throughout the entire vertebrate genome based on the extensive sequencing and analysis of lineage. His group has shown how discrete changes in diverse species, including the origin of the Y chromosome, other developmental enhancers drive species-specific the evolution of the immune system, and overall mutation changes important for facets of human gene expression. rates that underlie these processes. Bing Ren (University Many specialized microbial communities populate of California, San Diego) is a leader in the application niches that support human health or lead to disease. Meta- of genome-wide analysis of chromatin features to iden- genomic analysis of these communities, based on large- tify transcriptional regulatory elements; his studies have scale sequencing of DNA extracted from complex mix- provided a complementary method to identify functional tures of genomes, has provided quantitative representation DNA elements that drive gene expression in eukaryotes. of elusive microbes, many of which have yet to be cultured To interpret the quantitative output of such regulatory independently. Claire M. Fraser-Liggett (University of elements, one needs a sophisticated understanding of the Maryland School of Medicine) has pioneered the applica- cis-regulatory “grammar” that dictates how particular tion of metagenomics to diverse areas relating to human sets of binding sites generate precise outputs. David N. health. Phillip Hugenholtz (U.S. Department of Energy Arnosti (Michigan State University) studies this language Joint Genome Institute) has extended these approaches of transcriptional control using quantitative measurements to the most diverse, and least understood environments, of gene expression and fractional occupancy modeling, a including the termite gut, sludges, and prehistoric depos- method adapted from statistical physics. its, whose microbes may be the key to understanding In addition to these invited presentations, 12 short talks climate change as well as paths to a new energy future. will be chosen from the submitted abstracts. In the second genomics session, “Model Organisms and New Frontiers II,” we look at how the genomics of model David N. Arnosti is a professor of biochemistry and molecular systems paves the way to understanding the complex biology at Michigan State University and can be contacted transcriptional workings of metazoans. Expert compara- at [email protected]. Michael Washburn is the director of the tive genomicist Andrew G. Clark (Cornell University) Proteomics Center at the Stowers Institute for Medical Research has provided insights on the evolution of the Drosophila and can be contacted at [email protected].

New Frontiers in Genomics Symposium: Model Organisms and Quantitative Proteomics and New Frontiers I Symposium: The Role of Microbial Communities in Health Quantitative Proteomic and Disease, Claire M. Fraser-Liggett, University of Analysis of Protein Complexes Maryland School of Medicine Exploring the Dynamics of the Proteasome Sludges, Termite Hindguts, and Lake Vostok Interaction Network by Quantitative Proteomics, Lan Accretion Ice: What Metagenomics Can Tell Us Huang, University of California, Irvine About Microbial Communities, Phillip Hugenholtz, U.S. Department of Energy Joint Genome Institute MS Analysis of Protein Complexes, Carol V. Robinson, University of Cambridge Genome Regulation from a Distance, Edward M. Rubin, U.S. Department of Energy Joint Genome Dynamics of Protein Complexes, Michael Washburn, Institute Stowers Institute for Medical Research Symposium: Symposium: Model Organisms Quantitative Analysis of Post- and New Frontiers II translational Modifications Genomic Predictions of Regulatory Information: New Technologies for the Large-scale Analysis of Modeling and Measurements, David N. Arnosti, Proteins and Their Post-translational Modifications, Michigan State University Joshua J. Coon, University of Wisconsin, Madison Genomic Insights on Population Genetics, Biological Insights from Quantitative Analysis of Andrew G. Clark, Cornell University Tyrosine Kinase Signaling Networks, Forest M. White, Massachusetts Institute of Technology Decoding the Human Epigenome, Bing Ren, University of California, San Diego Identification and Initial Characterization of Histone Lysine Propionylation and Lysine Butyrylation Pathways, Yingming Zhao, University of Chicago

September 2009 ASBMB Today 29 2010 annual meeting continued Hypertension: Molecular Mechanisms, Treatment, and Disparities BY CRAIG E. CAMERON AND ROBERT HOOVER

CAMERON pproximately 1 billion people around the world suf- will consist of three symposia discuss- Afer from hypertension. According to a study by the ing these key subjects of “Molecular World Health Organization, hypertension was the risk fac- Mechanisms, Treatment, and Dispari- tor that contributed the most to worldwide mortality, with ties of Hypertension.” more than seven million deaths per year. Investigating the In the “Molecular Mechanisms of diagnosis, treatment, variability in patient populations, Hypertension” session, the seminars and underlying molecular mechanisms of hypertension will focus on mechanisms of regula- will likely be the key to controlling this disease. tion of salt reabsorption in the kidney. HOOVER Despite the longtime existence of multiple therapeutic The epithelial sodium channel (ENaC) agents for hypertension, the treatment of this complex dis- and the sodium chloride cotrans- ease continues to evolve. In the latter part of the previous porter (NCC) are key ion transport proteins that mediate century, this evolution centered on developing important salt reabsorption in the kidney. Hyperactivity disorders new classes of anti-hypertensive reagents. Now, changes involving either of these proteins result in hypertension in in treatment have begun to focus on defining the blood humans and animal models. Conversely, disorders involv- pressure at which treatment should be initiated, using the ing decreased activity result in hypotension. Thomas R. most efficacious combinations of therapeutic agents and Kleyman (University of Pittsburgh School of Medicine) determining the differ- will discuss how altera- ences between diverse tions in ENaC activity patient populations. The The recognition that affect blood pressure recognition that different “ as well as the impact of patient populations may different patient proteolytic cleaving on have different optimal populations may have activity of the channel. therapeutic regimens David Pearce (Univer- and rates of adverse out- different optimal sity of California, San comes is an important Francisco) will discuss factor toward improv- therapeutic regimens and how kinases and regula- ing the treatment of this rates of adverse outcomes tors of kinases impact disease. the activity of the Much of the drug is an important factor in channel. Robert Hoover development from the (University of Chicago) latter half of the previous improving the treatment will examine the role century was driven by a of this disease. of hormonal regulation greater understanding ” of NCC in the develop- of the molecular mecha- ment of hypertension. nisms underlying the regulation of blood pressure. All In the “Diagnosis and Treatment of Hypertension” ses- of the monogenic hypertension disorders that have been sion, John M. Flack (Wayne State University) will provide identified have involved disruption of sodium chloride an overview of the present paradigms for developing handling in the kidney. Understanding the regulation of individual treatment regimens for hypertensive patients. these salt reabsorptive pathways at the molecular level will Kenneth A. Jamerson (University of Michigan Health be important to developing future therapeutic interven- System) will discuss recent clinical studies focusing on the tions. The ASBMB Minority Affairs Committee has orga- efficacy and importance of combination therapies in the nized a hypertension theme for the Annual Meeting that treatment of hypertension. Treatment of what was previ-

30 ASBMB Today September 2009 ously described as “mild” hypertension results in improved African American patients. Jackson T. Wright, Jr. (Case morbidity and mortality. Shawna D. Nesbitt (University of Western Reserve University) will examine the evidence Texas Southwestern Medical Center) will discuss studies concerning the use of these key therapeutic agents in this indicating that even earlier treatment of “pre-hypertension” patient population. In addition to disparities in treatment is beneficial. of hypertension, there are also large differences in the rate In the “Disparities in Hypertension Treatment and and severity of complications of hypertension between dif- Sequelae” symposium, Lawrence Agodoa (National Insti- ferent patient populations. Janice P. Lea (Emory University tutes of Health) will address differences in the diagnosis School of Medicine) will discuss these differences in car- and treatment of hypertension based on gender and age. diovascular and renal outcomes and the potential reasons Many clinicians have developed biases concerning the use for these differences. of ACE inhibitors and angiotensin receptor blockers in MAC-sponsored Session on Mentoring Traditionally, the Minority Affairs Committee organizes Hypertension: Treatment, an issues-based session to contribute to the professional Disparities, and development of the ASBMB membership. This year’s theme is mentoring. Topics will include: mentoring stu- Molecular Mechanisms dents (Sydella Blatch, National Institutes of Health), men- Sponsored by the ASBMB Minority Affairs Committee toring at a distance (David Porush, MentorNet), mentor- ing women (Marilee Benore, University of Michigan), and Symposium: mentoring non-traditional students (Phillip Ortiz, Empire Molecular Mechanisms State College). of Hypertension Hormonal Regulation of the Sodium Chloride Craig E. Cameron is the Paul Berg professor of biochemistry Co-transporter, Robert Hoover, University of Chicago and molecular biology at Pennsylvania State University and can Epithelial Sodium Channels and Hypertension, be contacted at [email protected]. Robert Hoover is an assistant Thomas R. Kleyman, University of Pittsburgh School professor of medicine at the University of Chicago and can be of Medicine reached at [email protected]. Regulation of ENaC Trafficking, David Pearce, University of California, San Francisco

Symposium: Mentoring Diagnosis and Treatment Mentoring Students from Undergrads until of Hypertension Tenure, Sydella Blatch, National Institutes of Health The Importance of Combination Therapy in Neither Teacher, Parent, Friend, nor Boss: the Treatment of HTN, Kenneth A. Jamerson, MentorNet and Mentoring at a Distance, David University of Michigan Health System Porush, MentorNet Paradigms for the Diagnosis and Treatment of Mentoring Women- Strategies and Success HTN, John M. Flack, Wayne State University Stories, Marilee Benore, University of Michigan Pre-hypertension: Diagnosis and Treatment, Reaching out to Nontraditional Students, Phillip Shawna D. Nesbitt, University of Texas Southwestern Ortiz, Empire State College Medical Center

Symposium: Disparities in Hypertension Treatment and Sequelae Gender and Age Disparities in Hypertension, Compete For Best Poster Lawrence Agodoa, National Institutes of Health Awards at the Disparities in Cardiovascular and Renal Complications of Hypertension, Janice P. Lea, Emory University School of Medicine ASBMB Annual Meeting RAAS Inhibitor Containing Antihypertensive in Anaheim, California Regimens in African Americans: A Look at the Evidence, Jackson T. Wright, Jr., Case Western April 24-28, 2010 Reserve University

September 2009 ASBMB Today 31 minorityaffairs Patching the Pipeline BY REGINA STEVENS-TRUSS

n 1992, an issue of Science featured a series of MUST play a bigger role in mentoring and either move Iarticles called “Minorities in Science: The Pipeline the pipeline entry to an earlier point in education or be Problem” (1). The introductory report began with the more mindful of the leaky points. As college educators, following excerpt: we expend tremendous amounts of energy on the few “For 20 years, science has been wrestling with the minorities that remain in the pipeline and are already in pipeline problem: how to keep minorities from turn- college. But it is my belief that we can become patches ing off the obstacle-strewn path to careers in science, in the pipeline much sooner. mathematics, and engineering. Thousands of programs It is astounding that 17 years after the Science have been started since the late 1960s to bring diver- article was published this is still a conversation we are sity to the scientific workforce.” having. Nonetheless, we must continue to make the Fourteen years later, The Scientist published a sup- issue known and the problem heard and truly com- plement devoted to diversity. In it, there was an article mit to being the plugs in the pipeline. Albert Einstein by Kirsten Weir (2), who wrote, “It’s clear that many defined insanity as “doing the same thing over and over factors conspire to push underrepresented groups again and expecting different results.” The conventional out of the pipeline…There’s been a lot of noise [about wisdom of initiating programs that target students increasing diversity] for years, but there has been no solely at the college level has not been successful. systematic change.” As noted by Weir, “Failure to question conventional As a black Latina woman (or, as I like to think of wisdom contributes to persistent leaks in the scientific myself, a triple-cripple or a Trifecta), I often think about pipeline.” As science educators, we need to revisit cur- why and how I remained in the game despite my odds. rent practices and devise new ways of attacking this I am an immigrant from Central America and have lived continuing problem. in the United States for 35 years. My father strongly As a chemistry/biochemistry professor, I have made believed in education and its power and constantly an effort to patch the pipeline. By devising outreach/ emphasized its importance. Despite his preaching, mentor programs that make me and my college there were many societal influences that pulled me and students visible to the K-12 community, I believe that divided my attention; my peers, the media, and many we are imparting to children a sense of belonging, a adults in my life. So how did I end up in science? The sense of seeing themselves in the picture. We can and answer is two-fold: 1) my genuine love of science and MUST commit to devising ways in our communities to 2) the right role models at the right time. My eighth help patch the pipeline. From serving as mentors and grade math and art teachers had me convinced that encouraging our protogées to be mentors, to speaking I could do anything I wanted to. I already believed in out at every opportunity, we must not become compla- the power of education; they just convinced me that I cent and comfortable in our “successes” and allow this could excel at science and math. conversation about diversity to continue to fester. Why am I telling my story? Because it shows the Let’s patch that leaky pipeline now; there may not incredible role that mentoring plays in shaping young be a better time than the present. lives. What if all along the educational pipeline, minority students encountered mentors that served as “moni- Regina Stevens-Truss is an associate professor of chemistry tors” and helped them along? What if they were con- at Kalamazoo College and a member of the ASBMB Minority vinced at a young age that they “could do it?” All stud- Affairs Committee. She can be reached at [email protected]. ies point to the fact that by the time minority students get to high school, they have already been turned off References science. In fact, as pointed out by Weir, “Kids from 1. Culotta, E., and Gibbons, A., eds. (1992) Minorities in Science: The Pipeline underrepresented groups often give up before they’ve Problem 1st Annual Report. Science 258, 1175–1237. 2. Gallagher, R., ed. (2006) Diversity 2007: Measuring Effectiveness. The even entered the pipeline…” So, we as educators Scientist Supplement (November 2006).

32 ASBMB Today September 2009 lipid news Lipid Research in Australia BY STUART PITSON

ustralian biomedical science has long been known regulation by sphingolipids, lysophospholipids, phospha- Afor its seminal contributions to immunology, apop- tidic acid, and other lipids across a number of institutions, tosis, and protein biochemistry. The summary below, including the Centre for Cancer Biology in Adelaide, the written by Stuart Pitson, illustrates that there are underap- Garvan Institute, and the Centenary Institute in Sydney. preciated centers of excellence in lipid biochemistry and Quality work also continues on the regulation and biologi- biology as well. cal roles of the phosphoinositides at centers such as With a population one-fifteenth the size of the U.S. (21 Monash University in Melbourne, the University of Queen- million), the current lipid research in Australia represents sland, and the Garvan Institute. A few isolated pockets of a mere microcosm of the larger international effort. In resistance remain, however, such as acceptance in some particular, Australian research has played a significant and parts to the role of ceramide and sphingosine in apopto- longtime role in understanding the function and regulation sis. Again, this is almost certainly due to the pivotal initial of lipids such as cholesterol in cardiovascular disease (for and continuing work from Australian researchers in dis- example at the Heart Research Institute and University of covering and deciphering the role of Bcl-2 family proteins New South Wales (UNSW) and the Baker IDI Heart and in apoptosis instilling a natural bias toward this regulatory Diabetes Research Institute in Melbourne). Much of the model. With such strength in this area (most notably at strength in this area has been in response to increasing the Walter and Eliza Hall Institute in Melbourne), the cur- obesity rates that place Australia not far behind the U.S. rent lack of widespread collaborative efforts in Australia and has stemmed from support provided by the National to better understand the interplay that exists between the Health Priority Area framework of the National Health and Bcl-2 family and sphingolipid components of apoptotic Medical Research Council (the Australian equivalent of the regulation remains somewhat of a lost opportunity. U.S. National Institutes of Health). Lipid research in Australia has certainly diversified in Australia has also had longstanding strength in vesicu- the last decade, and, similar to the situation in the U.S., lar trafficking research at centers such as the Institute for is set to hold center stage like never before. Lipids have Molecular Bioscience (IMB) in Brisbane and the Garvan long been a focus in cardiovascular disease-related Institute in Sydney. While much of this research has conferences, but lipid-centric themes are now included traditionally focused on protein regulators, considerable in most Australian conferences, including ComBio (the work is now being carried out on the important role lipids annual conference of the Australian Society for Biochem- play in these processes. Considerable expertise in mem- istry and Molecular Biology—the other ASBMB), the brane biology (for example at the IMB and UNSW) and, Hunter Valley Cell Biology meetings, the Barossa Valley more recently, membrane microdomains as platforms for and Garvan Cell Signaling meetings, and the Lorne Can- signaling and mediators of diverse cellular functions has cer meetings. Notably, Australia will also host two other existed for some time in Australia. significant lipid meetings in the next year: the 28th World With the exception of phosphoinositides, the notion Congress and Exhibition of the International Society for of cellular signaling by other lipids was slow to be widely Fat Research (September 2009) and the 19th International accepted in Australia, especially compared with the U.S. Symposium on Plant Lipids (July 2010). This was probably due to the depth of Australian research The current strong interest in lipid research in Australia in deciphering the role of protein phosphorylation cas- and the recent development of a number of lipidomics cades in cellular regulation as well as the local strength facilities as well as the ever-increasing expertise in various and long history in proteomics in this country (the term lipid analyses bodes well for the future of the field in this “proteomics” was first coined in Australia), which naturally country. predisposed local researchers toward a protein-centric view of signal transduction. The concept of lipid signal- Stuart Pitson is a senior research fellow at the Centre ing is now commonplace, however, with considerable for Cancer Biology in Adelaide. He can be reached at Australian research efforts now being devoted to cellular [email protected].

September 2009 ASBMB Today 33 biobits asbmb journal science

Simple Heparan A CRAC Reporter Sulfate Purification The Ca2+ release- activated Ca2+ channel Glycosaminoglycan heparan sulfate (HS) is a com- (CRAC) is a well-known ponent of cell surface proteoglycans that is critical example of a store-op- in many biological and disease processes. How- erated channel system ever, the current methods of purifying HS are labori- in which intracellular ous, time consuming, and can sometimes result in depletion of an essen- alteration of native structure. This study, however, tial ion indirectly trig- puts forth a simple and rapid extraction and pu- gers channel activity. rification protocol employing phenol/guanidine/ A key intermediary in chloroform reagents known as RIP (rapid isolation the CRAC cascade is of proteoglycans). The authors demonstrated that stromal interaction mol- using a BODIPY fluorescent label in conjunction ecule 1 (STIM1), which with RIP purification allowed for structural analy- Removing the CMD of STIM1, senses ER calcium either through deletion (top panel, sis of HS at up to 100-fold higher sensitivity than depletion and then blue) or alanine substitution previous fluores- (bottom panel, blue) inhibits the binds to ORAI1, the fast inactivation of ORAI1 currents. cence detection pore-forming subunit of methods and CRAC. A cluster of seven negatively charged residues in 1000-fold higher the cytosolic part of STIM1 act to modulate ORAI1 bind- sensitivity than ing and activity, and, in this study, the researchers used standard UV de- patch-clamp analysis to examine this CRAC modulatory tection. With this domain (CMD). Deletion of CMD or substitution of the new technique seven negative residues with alanines severely reduced in hand, the au- or even abolished channel inactivation, whether in cells thors managed expressing exogenous ORAI1 or endogenous CRAC. RIP strategy for the rapid isolation of to observe novel heparan sulfate from tissues and cells. Interestingly, this reduction was not as pronounced for insights into HS endogenous CRAC or the homologous ORAI3, suggest- structural changes in Sulf1 (glucosamine endo- ing these two systems have additional factors that con- sulfatase) knock-out mice in vivo, which had been tribute to their inactivation processes. The researchers previously unattainable. RIP should emerge as a also found that decreasing intracellular Ca2+ chelators significant contributor in the field of glycomics and could promote ORAI1 inactivation, while substituting will enable better understanding of the structure- Ba2+ for extracellular Ca2+ completely abrogated activa- function relationships of HS and other glycosamino- tion, indicating this STIM1 feedback signal works in a glycans in complex biological systems. calcium-dependent manner.

Rapid Purification and High Sensitivity Analysis A CRAC Modulatory Domain (CMD) within of Heparan Sulfate from Cells and Tissues: STIM1 Mediates Fast Ca2+-dependent Toward Glycomics Profiling Inactivation of ORAI1 Channels Scott E. Guimond, Tania M. Puvirajesinghe, Mark Isabella Derler, Marc Fahrner, Martin Muik, A. Skidmore, Ina Kalus, Thomas Dierks, Edwin Barbara Lackner, Rainer Schindl, A. Yates, and Jeremy E. Turnbull Klaus Groschner, and Christoph Romanin J. Biol. Chem., published online July 13, 2009 J. Biol. Chem., published online July 21, 2009

34 ASBMB Today September 2009 biobits asbmb journal science For more ASBMB journal highlights go to www.asbmb.org

Caveolins Gather Alternative Approach Up the Fat to Biomarker Caveolins are small integral membrane proteins that Verification are responsible for forming surface invaginations While unbiased searches for known as caveolae in a variety of cell types. They are disease-associated proteins also involved in lipid storage and movement, as evi- can uncover hundreds (or more) denced by ectopic expression of caveolin-1 enhanc- differentially expressed proteins, ing fatty acid (FA) sequestration in membranes. In this comprehensive validation stud- study, the researchers further characterized the effect ies are required to weed out the of caveolin-1 and -3 expression on transmembrane false positives that constitute FA movement and distribution by labeling the outer most of these discoveries. Im- membrane leaflet of HEK293 cells with a fluorescent munoassays are a standard veri- marker (FPE) whose emission is quenched by the fication approach, but because presence of FA anions. Their real-time measurements MRM quantification reagents for clinical grade immu- indicate that caveolins-1 and -3 promote localiza- of the low abundance protein cardiac troponin noassays often exist for only a tion of FA anions I in six patients 0–24 handful of potential candidates, on the inner leaflet hours post-injury. alternative methods that are membrane through able to screen large protein sets are required. In this interactions with study, the researchers used multiple reaction monitor- basic amino acid ing (MRM) coupled with stable isotope dilution mass residues on their spectrometry (SID-MS), to develop a quantitative, mul- C termini. This tiplex assay that could detect low abundance plasma localization resulted proteins without the need for antibody enrichment. in enhanced cellular Next, they used their technique to assay six proteins of Imaging HEK293 cells labeled triglyceride ac- with FPE or BCECF shows that clinical relevance to cardiac injury (CRP, MRP14, MPO, cumulation and in- treatment with 20 μm oleate cTnI, cTnT, and NT-proBNP, which vary 3–4 levels of decreases fluorescence intensity creased protection due to fatty acid binding (FPE) and magnitude in their abundance) in six patients undergo- against FA-induced transmembrane diffusion (BCECF). ing alcohol septal ablation for hypertrophic obstruc- toxicity. Together tive cardiomyopathy. The researchers found that the with data from caveolin-deficient animal models, assays had a high degree of precision, reproducibility, these findings suggest an important role for caveolins and sensitivity in both inter- and intra-assay analysis, in modulating FA flux and storage, likely due to the indicating that SID-MRM-MS technology can be valu- ability of caveolin to facilitate the formation of lipid able in verifying novel or uncharacterized candidate rafts to buffer high FA levels. protein biomarkers.

Caveolins Sequester Fatty Acids on the Quantification of Cardiovascular Biomarkers Cytoplasmic Leaflet of the Plasma Membrane, in Patient Plasma by Targeted Mass Augment Triglyceride Formation, and Spectrometry and Stable Isotope Dilution Protect Cells from Lipotoxicity Hasmik Keshishian, Terri Addona, Jeffrey R. Simard, Tova Meshulam, Biju K. Pillai, Michael Burgess, D. R. Mani, Xu Shi, Eric Kuhn, Michael T. Kirber, Kellen Brunaldi, Su Xu, Marc S. Sabatine, Robert E. Gerszten, and Paul F. Pilch, and James A. Hamilton Steven A. Carr , published online July 15, 2009 J. Lipid Res. Mol. Cell. Proteomics, published online July 13, 2009

September 2009 ASBMB Today 35 firstcareersecond insights words From Lab Work and Genetics to Toxic Chemicals and Public Policy BY HOLLY DAVIES

don’t know whether my career path I spoke to the dean, he asked me to Ihas been a logical extension of my teach nutrition. That led to teaching varied interests or random happen- nutrition at another community college, stance. Five years ago, I never would and then the dean at that school asked have expected to be where I am today, me to teach environmental science working on chemical policy for the at the last minute for one quarter. I Washington State Department of Ecol- wouldn’t have applied to my current ogy. Instead, I thought I would be doing position at the Department of Ecology academic research in genetics. if I hadn’t been teaching environmental I went to Cornell University and got science. an undergraduate degree in biology with a concentration in genetics and My Current Job development. I also worked in several My current job is at the intersection of genetics labs while I was in college. what we know about chemicals and After college, I entered a Ph.D. program what we should do to protect human in the Department of Genetics at the health and the environment. I mainly Davies University of Washington (UW). I rotated work on persistent, bioaccumulative, Holly Davies received a B.S. in Biol- through several labs and chose to work and toxic chemicals (PBTs). These ogy with a concentration in genetics on RNA and translational control during chemicals last in the environment for and development from Cornell Uni- mouse spermatogenesis. For my post- a long time, build up in organisms and versity in Ithaca, NY in 1993 and a doc, I went to the National Institutes ecosystems, and are toxic. It has been Ph.D. in genetics from the University of Health to work on transcription and really interesting to learn about PBTs, of Washington in Seattle in 2000. mouse oogenesis. where they come from, and what we She worked as a postdoc at the I left NIH earlier than I expected and can do to get rid of them. My first proj- National Institutes of Health from went back to Washington when my ect was on lead, which can be found 2000 to 2004. In 2004, she moved husband was offered a job manag- everywhere. I now know more than to Washington State and taught ing salmon populations for a group of I ever thought I would about lead in biology at different schools before tribes. His job is in Olympia, the state consumer products and in the environ- joining the Washington Department capital. There is no genetics research in ment. I tagged along on a compliance of Ecology in 2007. At Ecology, she Olympia. visit to a local organ factory, as organ is working on reducing PBTs. Shortly after moving to Washington, pipes are made of lead. I was afforded I saw an ad for the perfect job teach- the opportunity to tour a prison to see ing genetics and molecular biology at its shooting range and what it does agencies. I also interact with the state a private university in Tacoma, about with lead ammunition. I learned more legislature, industry, environmental 30 miles away. I got the job, and it was than you can imagine about balancing groups, and others. During the last great, but it was only a 1-year visiting car tires with lead wheel weights. legislative session, I amended part assistant professor position. After that My agency is full of knowledgeable of a bill that was passed and signed was up, I started saying “yes” to every and helpful people, and I love learning by the governor. It’s satisfying to see job that came my way. I heard about an new things all of the time. I work with my words in law. We have also been opening to teach cell biology at a com- a lot of people doing different things working with other states on reforming munity college as an adjunct, but when within my agency and in other state chemical policy, especially for harmful

36 ASBMB Today September 2009 firstcareersecond insights words

chemicals in children’s products. Do but it is different when I am not talk- get a faculty position. I’ve always been you realize how little you know about ing to a group of Ph.D.s. It has also interested in law, so I looked into patent what is in your household products? been challenging to learn how a state law. If we hadn’t moved across the In the U.S., chemicals are presumed agency works and interacts with the country, I might have applied for a job safe until proven harmful. We often talk rest of state government. Even after as a patent agent at the U.S. Pat- about chemicals that cause can- 2 years, I still ask my boss all the time ent and Trademark Office in Virginia. cer, but it’s also important to look at about what group does what and what I spoke to some lawyers and patent developmental toxicity and endocrine the acronyms mean. After I had been agents in Seattle and Portland, but the disruption. I find my training in devel- at Ecology for a year, I saw an ad for a jobs are scarce, and both Portland and opment and reproductive biology is similar visiting assistant professor posi- Seattle are far from Olympia. I applied useful for that. tion at the university where I had taught for a human genetics policy fellowship While nobody asks me about genet- previously, and I couldn’t believe such a in Washington, D.C. Looking back, I ics anymore, and I haven’t run a gel or position had ever looked good to me. see it would have been crazy to leave looked through a microscope in almost my husband and two young children 5 years, I still use my training. As the Ideas That Did Not Work Out for a year, especially during the year our senior scientist in my section, I read a I did not take a direct path to my cur- oldest child started elementary school. lot of scientific papers and look at a lot rent job. I meandered a bit and started I applied for a job in management of data. I also use the logic and way down paths that did not work out. At consulting. In hindsight, I am glad that I of thinking that I learned in graduate some point, I realized that I didn’t feel did not get a job that requires so much school and my postdoc. I use my public strongly enough about my research to travel. Somehow, I ended up in the speaking and writing skills all the time, move my family to anywhere I could perfect place.

Systems Biology for Biochemists An ASBMB Sponsored Special Symposium October 22-25, 2009 Tahoe City, California Late Breaking Abstract Deadline: September 20, 2009

Organizer: Arcady Mushegian Stowers Institute for Medical Research education and training Changing Course: How Faculty Can Better Engage Students BY SHAWN R. DREW

“I hear, and I forget; I see, and I Uri Treisman, a graduate student at the University of remember; I do, and I understand.” California, Berkeley, wanted to understand why African Chinese Proverb American students were not doing as well in calculus as their Asian American counterparts. Through extensive here is a paradigm shift in the traditional role of a observations and careful data analysis, Treisman con- Tprofessor, from that of the “sage on the stage” provid- cluded that the major difference was that African American ing instruction in didactic lecture format to that of the students typically worked in isolation, while Asian Ameri- facilitator or the “guide on the side.” The transformation can students worked together and learned from each away from the teacher-centered approach to the student- other. Treisman then emphasized group learning and a centered approach is due, in large part, to advances in sense of community in his teaching, and the results were communication technology (e.g. the Internet) (1). However, dramatic—the African American participants outperformed many faculty members today have limited experience in not only other underrepresented minority students, but modern pedagogical skills that confer an engaged learning their Caucasian and Asian American classmates as well. environment since they, as students The Treisman model of peer collabo- themselves, were taught in the tra- ration is widely used today and exists ditional form of didactic instruction. Because of the in many closely related forms on some Below are various strategies that nature of discovery- 200-plus college campuses. science faculty can use to engage Providing challenging work and their students. “ based disciplines, fostering peer collaboration are science faculty useful strategies that engender an Strategies for academic atmosphere in which Engaging Students members have two students thrive. However, they should There are many strategies that additional tools to be considered with some degree of faculty from any academic disci- caution, as faculty members recog- pline can use to promote student engage students: nize that there are subtle caveats. For engagement for high academic i) active learning example, challenging curricula may achievement. One approach is lead to disengagement and stu- providing students with challeng- and ii) the research dents feeling overwhelmed if it is not ing work. This enables students to classroom. tempered with an appropriate level think critically about new concepts, of support where the learning goals explain their reasoning, defend are clear and achievable. Likewise, their conclusions, and explore alternative strategies and if peer collaboration is inappropriately conducted, it may solutions. Student engagement and achievement are pro- undermine” engagement if it threatens students’ self-effi- moted when instruction is rigorous (and yet still achievable) cacy and/or trust in peers. The student who is known as to allow students to develop and maintain their intellectual the “teacher’s pet” may not be well received among his ability. Intuitively, students become disengaged when the or her classmates for a collaborative project; therefore, work seems unchallenging and boring. faculty must be mindful of the interpersonal relationships Another method for student engagement is peer col- between students and dispel favoritism. laborative assignments, where students work in groups for shared interactions instead of working in isolation. Active Learning and Laboratory Research Research shows that peer collaborations provide better Because of the nature of discovery-based disciplines, learning experiences (2). For instance, in the late 1970s, science faculty members have two additional tools to

38 ASBMB Today September 2009 education and training

engage students: i) active learning and ii) the research followed by discussions and the opportunity to work classroom. Active learning comes in various forms, includ- collaboratively with one or two other students with similar ing problem-based learning (PBL) (3). Here, students are interests (employing the peer collaboration engagement presented with a problem and are asked to define an strategy). Faculty carefully designed each project to be approach for addressing the problem that is based on completed in a single semester, accommodating suf- their current knowledge of the subject. Students then ficient time for students to prepare an adequate literature learn the content of the subject matter and later partici- review (3–5 weeks), collect and analyze data (6 weeks), pate in exercises designed to determine how much they and perform written and oral assessments (4–6 weeks). learned. A key to the success of PBL is that the problem To accomplish the tasks in the time allowed, projects must be open-ended and were narrow in scope and not strictly defined. As such, employed proven laboratory this creates situations similar …to achieve dynamic methodologies (for example, to those that real world learning environments, some of the student research scientists face which yield “ faculty must go beyond projects were “subcloning unexpected results that can a gene encoding a bacte- be a source of new hypoth- the status quo of the rial lipase” and “cloning eses and major theoretical conventional didactic a gene encoding a novel insights (4). thermostable esterase”). The Although many proven delivery approach and students’ projects were not methods for incorporating incorporate various designed as a techniques active learning into postsec- course for conducting labora- ondary courses are available strategies that purposefully tory experiments, but rather (5), they are far from the engage students in the activities in which students norm as faculty struggle to took ownership of their learn- implement them. The barri- learning process. ing. Grades were not based ers to incorporation include on specific research findings inflexible curricula, insufficient time to prepare lessons, at the end of the semester, but on the level of effort and concern about the potential for not accomplishing speci- application” that students bestowed through the scientific fied learning goals, and fear of the unknown. Researchers process. The result was nearly a three-fold increase in at Cornell University (6) have shown that when educators independent research enrollment and the exposure of 80 are able to address these concerns and become increas- percent of biology graduates to research (10). ingly comfortable with this approach, a range of benefits Another institution (with a grant from National Sci- ensue; e.g. increased student motivation and interest in ence Foundation’s Course Curriculum and Labora- science and a greater degree of critical thinking leading tory Improvement) which assessed outcomes from its to deeper understanding. research classroom courses found that science majors Many science faculty members recognize that a good had a deeper appreciation and understanding of science way to supplement pedagogy is for students to conduct that guided their career trajectory post-undergraduate extracurricular laboratory research. However, due to training (11). This is an important concept, as many limitations in human and fiscal resources, most institu- science undergraduates, in particular those majoring in tions can only offer this type of training to a small subset biology, often view graduate school as a last resort if they of students, typically those in an externally funded sci- do not get accepted into medical school. As a conse- ence program. quence, such students enter graduate programs under- There are well documented and strongly supported motivated, under-prepared, and uninformed about the benefits of research exposure, in particular for undergrad- nature of academia. Providing research training through uate students (7-9). For example, the United States Air the research classroom strategy during the undergradu- Force Academy developed a classroom-based research ate years better prepares science students for the rigors program in their biology department. Students were of graduate school. presented with a range of potential research projects, In summary, to achieve dynamic learning environments,

September 2009 ASBMB Today 39 educationand training continued

faculty must go beyond the status quo of the con- ventional didactic delivery approach and incorporate various strategies that purposefully engage students in the learning process. Science faculty members Department of Health and Human Services who have used the various engagement strategies National Institutes of Health presented in this paper have witnessed increased National Heart, Lung, and Blood Institute student motivation, interest in science, and a deeper Division of Intramural Research understanding of the subject matter. Such students Bethesda, MD are motivated to learn as they pursue higher order Tenure Track/Tenured Position learning; they also experience other benefits, such Basic Biomedical Research as improved communication and problem-solving The Division of Intramural Research (DIR) of the National Heart, Lung and Blood skills, heightened critical thinking and inquiry, and Institute (NHLBI) is seeking an outstanding scientist to initiate and direct an inde- increased confidence. The benefits outweigh any pendent research program in basic science on the NIH campus in Bethesda, implementation challenges faculty faced incorporat- MD. The area of expertise of the candidate is less important than his/her dem- ing these modern pedagogical modalities. Through onstrated ability to conduct outstanding independent research in areas within the broad biomedical research interests of the DIR. The areas of expertise may implementation of these engagement strategies, include but are not limited to: cell biology, developmental biology, molecular biol- students may provide a modern take on the Chi- ogy, immunology, stem cell biology, genetics, genomics, physiology, biochem- nese proverb: “Because I hear, see, and do, I am istry, bioenergetics and metabolic regulation, biophysics, biomolecular struc- engaged, and I understand.” ture and dynamics, systems and synthetic biology, and biomedical engineering. Technical approaches may include: high-resolution microscopy, x-ray spectros- Shawn R. Drew is the MARC Program Director of the copy and imaging, clinical robotics, nanotechnology, chemical biology, compu- tational, and theoretical methods. The existing faculty is an outstanding group MORE Division, Program Director of Biostatistics Training, of internationally recognized biomedical researchers covering a wide range of and Chair of the Committee to Maximize Representation basic and clinical research topics (please see http://dir.nhlbi.nih.gov/) comple- at the National Institute of General Medical Sciences mented by the other research institutes within the DIR (please see http://www. (National Institutes of Health). She can be contacted at nih.gov/science/#campus). [email protected]. The DIR environment provides the opportunity to perform creative and innova- tive science unconstrained by traditional support systems available at academic or private research institutions. This is enhanced by outstanding research core facilities in optical and electron microscopy, transgenic and knockout mouse References production, mouse phenotyping, proteomics, genomics, and flow cytometry/cell 1. Garrison, D. R., and Vaughan, N. (2008). Blended Learning in Higher sorting as well as world-class seminar series and symposia. DIR faculty can Education: Framework, Principles, and Guidelines. Jossey-Bass, San Francisco, CA. participate in Graduate Partnerships Programs (http://gpp.nih.gov) with many 2. Goodsell, A., Maher, M., Tinto, V., Smith, B. L., and MacGregor, J. academic programs around the world as a means of recruiting graduate stu- (1992). What Is Collaborative Learning? Collaborative Learning: A Sourcebook for Higher Education, National Center on Postsecondary dents, and extensive career guidance and development resources are available Teaching, Learning, and Assessment; Pennsylvania State University. on campus for post-doctoral trainees. 3. Allen, D. E. (1996). Bringing Problem-based Learning to the Introductory Biology Classroom in Student-Active Science: Models Candidates must have an M.D., Ph.D., or both and have an outstanding of Innovation in College Science Teaching, ed. A. P. McNeal and C. record of research accomplishments as evidenced by publications in major D’Avanzo. Phil.: Sauders College Publishing, 259–278. peer-reviewed journals. The position can be filled as a tenure-track or tenured 4. Dunbar, K. (2000) How Scientists Think in the Real World: Implications for Science Education. Journal of Applied Development position, but preference will be given to senior post-doctoral fellows or faculty Psychology 21, 49–58. who are still in the early stages of their research careers. The successful can- 5. Handlesman, J., Ebert-May, D., Beichner, R., Bruns, P., Chang, A., DeHann, R., Gentile, J., Lauffer, A., Stewart, J., Tilghman, S. S., and didate will be offered a competitive salary commensurate with experience and Wood, W. B. (2004) Scientific Teaching. Science 304, 521-522. qualifications, and will be assigned ample research space, supported positions, 6. Trautmann, N., MaKinster, J., and Avery, L. (2004) What Makes Inquiry so Hard? (And Why Is It Worth it?) Proceedings of the NARST and an operating budget. Appointees may be US citizens, resident aliens, or 2004 Annual Meeting, Vancouver, BC, Canada. non-resident aliens with or eligible to obtain a valid employment authorized visa. 7. Halaby, R. (2001). Promoting Undergraduate Research in Science. Complete applications must be received by November 1, 2009. Please submit Scientist 15, 35. 8. National Research Council (1996). From Analysis to Action: a curriculum vitae, brief (not to exceed 3 pages) statement of research interests Undergraduate Education in Science, Mathematics, Engineering, and three letters of reference in .pdf or MS word format only (no paper applica- and Technology. Washington, D.C.; National Academy Press. Also available online at www.nap.edu/catalog/9128.html. tions will be accepted) to: 9. National Research Council (2003). BIO2010: Transforming Undergraduate Education for Future research Biologists. National Robert S. Balaban, Ph.D., Scientific Director, NHLBI Academy Press, Washington, D.C. c/o Michelle Renehan, [email protected] 10. Snellman, E., Krueger, J. A., and Unangst, E. T. (2005) Moving Research into the Classroom: Successful Adaptations at a Service Academy. Journal of College Science Teaching, March/April, 24–28. DHHS and NIH are Equal Opportunity Employers. Application from women, 11. Kight, S. Gaynor, J. J., and Adams, S. D. (2006) Undergraduate minorities and persons with disabilities are encouraged. Research Communities: A Powerful Approach to Research Training. Journal of College Science Teaching, July/August, 34-39.

40 ASBMB Today September 2009 Journal of Biological Chemistry New P450 Collections

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Moving science forward scientific meeting calendar

SEPTEMBER 2009 OCTOBER 2009 2009 Swiss Group for Mass Spectrometry Meeting 50th International 3rd ESF Functional OCTOBER 28–29, 2009 Conference on the Genomics Conference BEATENBERG, SWITZERLAND Bioscience of Lipids OCTOBER 1–4, 2009 www.sgms.ch SEPTEMBER 1–5, 2009 INNSBRUCK, AUSTRIA REGENSBURG, GERMANY www.esffg2008.org NOVEMBER 2009 www.icbl2009.de 3rd Central and Eastern Annual Biomedical British Atherosclerosis European Proteomics Research Conference Society Meeting on Conference for Minority Students Genetics of Complex OCTOBER 6–9, 2009 NOVEMBER 4–7, 2009 Diseases BUDAPEST, HUNGARY PHOENIX, AZ SEPTEMBER 17–18, 2009 www.chemres.hu www.abrcms.org/index.html CAMBRIDGE, United kingdom www.britathsoc.org SACNAS National Mass Spec Europe Conference: Improving NOVEMBER 5–6, 2009 MWLA Annual the Human Condition: BARCELONA, SPAIN Scientific Forum Challenges for www.selectbiosciences.com SEPTEMBER 25–27, 2009 Interdisciplinary Science CINCINNATI, OH OCTOBER 15–18, 2009 7th Annual World www.lipid.org DALLAS, TX Congress on the Insulin www.sacnas.org/confnew/confclient Resistance Syndrome HUPO 8th Annual World NOVEMBER 5–7, 2009 Congress 7th Euro Fed Lipid Congress SAN FRANCISCO, CA SEPTEMBER 26–30, 2009 OCTOBER 18–21, 2009 www.insulinresistance.us TORONTO, CANADA GRAZ, AUSTRIA www.hupo2009.org/default.htm www.eurofedlipid.org/meetings/graz/ Annual Meeting of the Society for Glycobiology World Congress on 36th Federation of NOVEMBER 12–15, 2009 Oils and Fats and Analytical Chemistry and SAN DIEGO, CA 28th ISF Congress Spectroscopy Societies www.glycobiology.org SEPTEMBER 27–30, 2009 (FACSS) SYDNEY, AUSTRALIA OCTOBER 18–22, 2009 American Heart Association www.isfsydney2009.com LOUISVILLE, KY Scientific Sessions 2009 www.facss.org NOVEMBER 14–18, 2009 5th Congress of the ORLANDO, FL Portuguese Proteomics Systems Biology www.scientificsessions.org Network and 1st for Biochemists th International Congress 4 Barossa Meeting: OCTOBER 22–25, 2009 Cell Signaling in Cancer on Analytic Proteomics TAHOE CITY, CA SEPTEMBER 30– Organizer: Arcady Mushegian, and Development OCTOBER 3, 2009 Stowers Institute for Medical NOVEMBER 18–21, 2009 CAPARICA, PORTUGAL Research BAROSSA VALLEY, SOUTH AUSTRALIA www.cqfb.fct.unl.pt www.asbmb.org/meetings sapmea.asn.au/conventions/ signalling09/index.html 6th International Congress Bioactive Lipids in 20th International on Heme Oxygenases in Cancer, Inflammation, Biology and Medicine Symposium on and Related Diseases Glycoconjugates SEPTEMBER 30– (11th International OCTOBER 4, 2009 NOVEMBER 29– MIAMI BEACH, FL Conference) DECEMBER 4, 2009 www.hemeoxygenases.org OCTOBER 25–28, 2009 SAN JUAN, PR CANCUN, MEXICO www.glyco20.org www.bioactivelipidsconf.wayne.edu scientific meeting calendar

DECEMBER 2009 APRIL 2010 11th International Symposium on the Genetics 49th Annual Meeting Keystone Symposium— of Industrial Microorganisms of the American Society Diabetes JUNE 28–JULY 1, 2010 for Cell Biology APRIL 12–17, 2010 MELBOURNE, AUSTRALIA DECEMBER 5–9, 2009 WHISTLER, CANADA www.gim2010.org SAN DIEGO, CA www.ascb.org/meetings 4th ESF Functional AUGUST 2010 Genomics Conference th JANUARY 2010 APRIL 14–17, 2010 9 International Mycological DRESDEN, GERMANY Congress (IMC9): Keystone Symposium— www.esffg2010.org The Biology of Fungi Adipose Tissue Biology AUGUST 1–6, 2010 JANUARY 24–29, 2010 ASBMB Annual Meeting EDINBURGH, UNited Kingdom KEYSTONE, CO APRIL 24–28, 2010 www.imc9.info www.keystonesymposia.org Anaheim, CA www.asbmb.org/meetings.aspx 14th International 5th Human and Medical Congress of Immunology Genetics Meeting AUGUST 22–27, 2010 JANUARY 28–30, 2010 MAY 2010 KOBE, JAPAN www.ici2010.org STRASBOURG, FRANCE 6th International www.assises-genetique.org/fr Atherosclerosis Society Workshop on High Density sEPTEMBER 2010 FEBRUARY 2010 Lipoproteins British Mass Spectrometry 15th Annual Proteomics MAY 17–21, 2010 Society Meeting Symposium WHISTLER, CANADA SEPTEMBER 5–9, 2010 www.athero.org FEBRUARY 4–7, 2010 CARDIFF, WALES LORNE, AUSTRALIA www.bmss.org.uk www.australasianproteomics.org JUNE 2010 HUPO 9th Annual AAAS Annual Meeting 3rd European Workshop World Congress FEBRUARY 18–22, 2010 on Lipid Mediators SEPTEMBER 19–24, 2010 SAN DIEGO, CA JUNE 3–4, 2010 SYDNEY, AUSTRALIA www.aaas.org/meetings PARIS, FRANCE www.hupo.org www.workshop-lipid.eu Biophysical Society OzBio2010 th 53rd Annual Meeting 8 International Conference SEPTEMBER 26– FEBRUARY 28–MARCH 4, 2009 on Hyaluronan of the OCTOBER 1, 2010 BOSTON, MA International Society for MELBOURNE, AUSTRALIA www.biophysics.org/Default. Hyaluronan Sciences www.asbmb.org.au/ozbio2010 aspx?alias=www.biophysics. JUNE 6–11, 2010 org/2009meeting KYOTO, JAPAN www.ISHAS.org APRIL 2011 MARCH 2010 SEB Annual Main Meeting ASBMB Annual Meeting Keystone Symposium– JUNE 30–JULY 3, 2010 APRIL 9–13, 2011 PRAGUE, CZECH REPUBLIC Biomolecular Interaction WASHINGTON, D. C. www.sebiology.org/meetings Networks: Function and www.asbmb.org/meetings.aspx Disease Keystone Symposium— MARCH 7–12, 2010 QUEBEC CITY, CANADA Bioactive Lipids: www.keystonesymposia.org Biochemistry and Diseases JUNE 6–11, 2010 KYOTO, JAPAN www.keystonesymposia.org