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“A“A MolecularMolecular ExplorationExploration ofof thethe Cell”Cell” ASBMB Annual Meeting and 8th IUBMB Conference JuneJune 12-16,12-16, 20042004 Boston, Massachusetts Dr. Roderick MacKinnon ASBMB Members Share Nobel See Page 8

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AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY NOVEMBER 2003, Volume 2, Issue 8 features

3 Marc Kirschner to Head Harvard’s New Systems Biology Department

4 Seeking Balance in Age of Terrorism

6 Texas Stem Cell Advocates Meet, Organize 13 10 Life Scientist Salaries Reported

12 Protein Modifications and Turnover

ON THE COVER: 14 Cellular Organization and Dynamics

8 ASBMB Members 16 Integration of Signaling Mechanisms Share Nobel Prize 18 Lasker Award Honors Robert Roeder

20 Harvard’s Jack Strominger to Receive ASBMB-Merck Award

departments 22 NIH News 14 24 Biotech Business 27 Career Opportunities 28 Calendar

BRONZE AWARD WINNER 2003 LETTERS

ASBMB Today is a monthly publication of The American Society for Biochemistry and Molecular Biology A Crisis Developing in Biology Officers Bettie Sue Masters President n a recent publication, ASBMB virtue of the guidelines used and publi- Judith S. Bond President-elect Albert E. Dahlberg Secretary Today, August 2003, Sydney cized in making the awards and by the Kenneth E. Neet Treasurer I Brenner contends, quote, fact that the Nobel Committee has Thomas Blumenthal Councilor “there is now a crisis developing in high regard for the merit of the Lasker William R. Brinkley Councilor biology, in that completely unstruc- Award. Could a criteria of merit for the Lila M. Gierasch Councilor Frederick P. Guengerich Councilor tured information does not achieve Lasker Award address not only the dis- William J. Lennarz Councilor understanding.” The Scientist, in an covery meriting the Award but also the Alexandra C. Newton Councilor editorial describes the problem collation and integration of data Merle S. Olson Councilor Peter J. Parker Councilor as, quote, “data overload, absence which led to the discovery? William L. Smith Councilor of reproducibility, and lack of an A recent review which I wrote was Non-Voting Members appropriate conceptual framework.” published in Cardiovascular Engineering, George M. Carman Another recent article defines the prob- An International Journal, Vol. 2, No. 3, Chair, Meetings Committee lem as, quote, “Separating the Curd September 2002. That review, Athero- John D. Scott from the Whey.” Still another article genesis: Historical Perspective, Bio- Alexandra C. Newton Julio Celis has the heading, “Databases Grow, and chemical Mechanism, and Current Co-chairs, 2004 Program Committee Grow, —- and GROW.” Status, provides examples of discovery Marion H. O’Leary J. Ellis Bell I recently wrote to Dr. Brenner on based on collation and integration of Co-chairs, Education and Professional this problem and defined it by stating unstructured data. Also, see Naturwis- Development Committee that all of us are literally drowning in senschaften 80:547-555, 1993. William R. Brinkley Chair, Public Affairs Advisory Committee data because this immense mass of With best regards, I am, Peter A. Rubenstein uncollated and non-integrated data Sincerely, Chair, Publications Committee does not permit understanding biolog- Laurence Pilgeram, Ph.D. Phillip A. Ortiz Chair, Minority Affairs Committee ical mechanisms or function. The crux PO Box 1583 Herbert Tabor of the problem seems to be that we Goleta Station Editor, JBC have developed a current generation of Santa Barbara, California 93116 Ralph A. Bradshaw scientists with a mind set on automa- Editor, MCP Edward A. Dennis tion who use this generation of data as Editor, JLR a substitute for thinking and the hard Tell Us What difficult mental work required for mak- Editorial Advisory Board You Think Irwin Fridovich ing sense out of the data. We seem to Richard W. Hanson have forgotten that computers do not Bettie Sue Masters think. Garbage in, garbage out. We appreciate receiving let- Evan J. Sadler In wrestling with this problem, the Robert D. Wells ters that are suitable for publica- question arose as to how can we cope tion from ASBMB members Comments with this problem of re-orienting our regarding issues of importance Please direct any comments or questions thinking and that of students back to or commenting on articles concerning ASBMB Today to: the essence of scientific discovery, appearing in ASBMB Today. Let- John D. Thompson rather than mindless generation of ters should be sent to the editor, Editor, ASBMB Today data. It has become so bad that our 9650 Rockville Pike John Thompson, at the address Bethesda, MD 20814-3996 current generation of editors consider found at left. Letters must be Phone: 301-634-7145; Fax: 301-634-7126 data to be outdated or meaningless if it E-mail: [email protected] signed and must contain the is more than five years old. writer’s address and telephone For information on advertising It seems to me that the members of contact FASEB AdNet at 800-433-2732 number. The editor reserves the ext. 7157 or 301-634-7157, or the Lasker Award Jury are in a unique right to edit all letters. email [email protected]. position to address this problem by

2 ASBMBToday NOVEMBER 2003 Marc Kirschner to Head Harvard’s New Systems Biology Department arvard Medical School has eling and quantitative measurement. ics, computer sciences, physics, and made a significant commit- In its modern guise it attempts to yield engineering, as well as traditional bio- H ment to the emerging field of molecular descriptions of complex cel- medical fields; talent from broad disci- systems biology in the creation of the lular and multicellular systems. It fills plines that can develop the theoretical Department of Systems Biology (DSB), an important current gap in both framework for complex systems biol- one of the first such department-levels teaching and research.” ogy problems. More than 20 fulltime in the nation. The Department of Sys- “It is worrying that we do not under- faculty will be recruited and the new tems Biology will be Harvard Medical stand how most drugs work and essen- Systems Biology Department will School’s first completely new depart- tial that we know in detail how both receive significant initial funding from ment in more than two decades and, genetic mutations and the environ- Harvard University and Harvard Med- with more than 20 faculty recruit- ment contribute to disease,” said ical School. The new department will ments expected, will be one of its Joseph B. Martin, Dean, Harvard Med- have special programs for the educa- largest departments. ical School. “Answering such questions A quantitative understanding of an requires building predictive models of “Systems biology is a entire subcellular, cellular, or organism cells, organs, and ultimately, organ- system could dramatically speed drug isms. And this requires not only logical extension of discovery, by allowing one to predict advanced computational models but physiology and the effects of attacking a specific target the acquisition of new quantitative within the context of the complex cel- data, often with new methods capable biochemistry...” lular circuits. New drugs often fail after of interrogating the activity of a large Dr. Marc Kirschner the expenditure of millions of dollars, number of genes within whole cells or because the effect on a single gene or whole organisms. In evaluating this protein target in the test tube fails to challenge, we reached the conclusion tion of physical scientists in biology have the predicted effect when tested that the scale of the effort required and special core facilities to promote in the human body. demands a new department.” interaction between disciplines. DSB “As we understand more about the “This type of focused, department- will also be inter-institutional, linking tiniest pieces that we are made of, it based program will help to define and faculty from the Medical School with becomes increasingly clear that we do stimulate the exciting interdisciplinary faculty at its affiliated hospitals and not understand how they work field of systems biology, which needs Harvard University. together as systems,” said ASBMB strong leadership right now,” said member Dr. Marc Kirschner, the first Bruce Alberts, President of the National About the new chair of the new department. “We Academy of Sciences and a member of department’s leader need to build on the foundation of the outside review panel that helped Dr. Kirschner, a pioneering biological molecular biology to construct an Harvard Medical School decide on pri- scientist, has extensive experience understanding of the architecture of orities for the coming years. “With the both developing new departments and the cell and how cells cooperate across guidance provided by Marc Kirschner, creating interdisciplinary efforts. He organ systems, with a predictive model a proven builder of new departments, I has received Canada’s Gairdner Award, of physiology as the ultimate goal. would expect this new endeavor to Israel’s Shacknai Prize, and ASBMB’s “In many ways systems biology is a have a profound impact on biology William C. Rose Award (2001), and in logical extension of physiology and over the long term.” December of this year, will receive the biochemistry and like these fields it The new department will include American Society for Cell Biology’s E.B. has strong roots in mathematical mod- faculty from areas such as mathemat- Wilson Medal.

NOVEMBER 2003 ASBMBToday 3 Seeking Balance in an By John D. Thompson, Editor or life science researchers, a to lead a new oversight system. Made Recombinant DNA Advisory Com- balanced approach is neces- up of top scientists and national-secu- mittee (RAC). With their expanded F sary in order to defend rity experts, the board would provide duties, it is anticipated that there against bioterrorism without hindering expert scientific advice on the relative would be only rare cases in which research that is essential to the health risks and benefits of new technologies, IBCs could not decide whether a pro- of the nation’s people. and alert the government to new posed experiment should proceed. That is the conclusion of a report, opportunities for the development of Such cases would be referred to the Biotechnology Research in an Age of Ter- vaccines and antibiotics. It also would RAC, and possibly to the NIH Direc- rorism: Confronting the Dual Use promote ongoing dialogue between tor, who could consult with the Dilemma, released last month by the scientists and security experts, and National Science Advisory Board for National Academies’ National Research advise the government on how life sci- Biodefense. Council (NRC). entists could mitigate the risks of The NRC report rejected the estab- bioterrorism. Reviewing and lishment of a “top-down,” system Publishing Research requiring mandatory review of Reviewing Planned Results experiments, due to concern that Experiments The new system also would include this would slow the progress in The report proposes a tiered system the review of study results from any biotechnology, “which has revolu- of review to identify experiments that experiments of concern that are tionized the practice of medicine,” raise concerns due to their high poten- approved. However, it states that deci- according to Gerald Fink, Professor tial for misuse. These are experiments sions on whether results should be of Genetics at the Whitehead Insti- that would: published need to be within the tute for Biomedical Research, Massa- ❖ demonstrate how to render human purview of the scientific community chusetts Institute of Technology, or animal vaccines ineffective; and not, the committee emphasized, who chaired the committee that ❖ confer resistance to therapeutically the federal government. wrote the report. useful antibiotics or antiviral agents This self-governing approach is dif- The report also rejects restrictions on for humans, animals, or crops; ferent from the federal government’s the freedom of journal editors to pub- ❖ enhance the virulence of human, restriction on public access to “sensi- lish federally funded fundamental animal, or plant pathogens, or make tive but unclassified” information in research, unless the federal govern- nonpathogens virulent; the life sciences. Experience shows, ment had previously given it a ❖ increase the transmissibility of the report noted, that vague cate- national security classification. pathogens; gories of this kind generate great “The challenge is for the scientific ❖ alter the host range of pathogens; uncertainties among both scientists community to develop a system that ❖ enable the evasion of diagnostic or and government officials, and permits fundamental research to pro- detection methods; or inevitably stifle scientific creativity— ceed unimpeded, while identifying ❖ enable the weaponization of biologi- and weaken national security. research with great potential for mis- cal agents or toxins. Ongoing discussion among people use,” according to the NRC report. The first tier of review begins with involved in publishing scientific jour- The report recommends that the a research establishment’s Institu- nals–and between journal editors and Department of Health and Human Ser- tional Biosafety Committee (IBC). national-security experts–is essential to vices create an independent National IBCs conduct their reviews using creating an effective system of review Science Advisory Board for Biodefense guidelines developed by NIH’s and oversight, the committee said. The

4 ASBMBToday NOVEMBER 2003 Age of Bioterrorism proposed National Science Advisory that has not received national security committee’s proposed oversight sys- Board for Biodefense could be a classification, except as provided in tem for the United States, ultimately resource for producers of journals in applicable U.S. statutes.” promoting greater security around the life sciences by, for example, pro- the world. viding access to examples of review Engaging the The study was sponsored by the procedures currently in use. Scientific Community Sloan Foundation and the Nuclear The general principle of the federal To bring about significant and last- Threat Initiative. Copies are available government’s National Security Deci- ing change, the NRC report concludes, from the National Academies sion Directive 189 remains valid and the American scientific community Press; tel. 202-334-3313 or 1-800- should continue to be the basis for U.S. must become more deeply engaged in 624-6242 or on the Internet at policy, the report says. That directive this issue. At the same time, a commit- http://www.nap.edu. The cost of the states, “No restrictions may be placed ment is needed from the international report is $40 plus shipping charges of upon the conduct or reporting of fed- scientific and policymaking commu- $4.50 for the first copy and $.95 for erally-funded fundamental research nities to develop a counterpart to the each additional copy.

NOVEMBER 2003 ASBMBToday 5 Texas Stem Cell Advocates Meet, By Peter Farnham, ASBMB Public Affairs Officer he stories came quietly, matter- face a similar fight in the next legisla- has asked for an interim study on stem of-factly, one by one around tive session and called the October 5 cell research—a clear signal that the T the room, each one from a meeting to organize for the next battle. ban will be revisited. family member with a child or other TAMR is made up of individual During the organizational portion of loved one suffering from a chronic and patient advocates, most suffering from the meeting, ASBMB President Masters so far incurable illness. Most poignant of one or more of the worst scourges of the and several of her scientific colleagues all was this comment from a mom—“I human condition still extant, as well as said that they would continue to sup- was the mother of a juvenile diabetic.” representatives of Texas chapters of such port TAMR, as ASBMB and FASEB did This and other stories were heard dur- groups as the Parkinson’s Action Net- last spring. ing a meeting in Austin, Texas on Octo- work, the Juvenile Diabetes Research TAMR’s efforts were spearheaded by ber 5, that marked the first formal steps Foundation (JDRF), the Parkinson’s Beckie McCleery and Judy Haley, both of grass roots research advocates in Advocacy Coalition, Texans to Cure active in their local chapters of the Texas to organize themselves into some- Paralysis, and others. Also present at the Juvenile Diabetes Research Foundation. thing more than a loose collection of meeting were members of the Texas leg- “This meeting was very successful,” individuals and smaller organizations islature who helped defeat the ban, as Mrs. McCleery said. “We need to take with a common letterhead—Texans for well as representatives of ASBMB—Presi- TAMR to the next level to ensure that the Advancement of Medical Research dent Bettie Sue Masters and a staff vital research into regenerative medi- (TAMR)—but not much else in the way member—and representatives of FASEB, cine is not put at risk.” TAMR is form- of tangible assets. including Dr. Ellen Kraig, a member of ing an organizing committee to Not that the group hasn’t been effec- AAI and the FASEB Science Policy Com- identify its future shape and address tive up to now—far from it. TAMR was mittee, and Jill Adleberg, with the such issues as tax status, incorporation, formed just last spring and, operating on FASEB Office of Public Affairs. and fund-raising. TAMR also gave Rep. heart, energy, and hard work to make up A videotape of the floor debate on the Eissler an award recognizing his efforts for an almost non-existent budget, its SCNT ban in the Texas legislature was to defeat the proposed ban. accomplishments in the state legislature shown at the meeting, and the debate Both women spoke with ASBMB were little short of amazing. revealed a number of scientific miscon- Today after the meeting. Judy Haley From a standing start, this collection ceptions about stem cell research as well became involved in diabetes advocacy of ordinary people enduring extraordi- as what the federal anti-cloning legisla- in 1990, when two of her three chil- nary suffering managed to defeat legis- tion proposed by Senator Sam Brown- dren were diagnosed with Type-1 dia- lation that would have outlawed back (R-KS) actually says. Nevertheless, betes. “They were 10 and 12 when somatic cell nuclear transfer—so-called an observer was struck by the overall they were diagnosed,” she said. “The research cloning. Even more remark- quality of the videotaped debate, con- only way our family could cope with able, the victory was won despite the ducted with a level of comity often lack- this disease was to proactively go after fact that the well-financed and organ- ing in political discussions on such it. It wasn’t enough to give them ized effort to pass it was backed by the emotional topics. insulin shots; we had to try to fix the politically powerful right-to-life move- The videotape was followed by a disease. So, every way we can, we are ment, introduced by a rising star in panel led by Rob Eissler, a freshman out there fighting.” Republican politics in the Lone Star Republican state legislator and a key Beckie McCleery had her own story. State—Rep. Phil King, chair of the state ally against the ban. “We’ve bought “My son has juvenile diabetes. He’s 18 Regulated Industries Committee—and two years,” he said of the victory. How- now, and was diagnosed when he was supported by the Republican leadership. ever, he cautioned that the proposed 14. Our world literally turned upside TAMR’s weeks of hard work literally ban would certainly come up again. down. There’s no history of the dis- did not end until the last few hours of The Texas legislature meets every two ease in our family and we were com- the 2003 legislative session, when its years, and during the off-year members pletely unprepared for it. We know allies won the final showdown by a can commission “interim studies” on juvenile diabetes is an autoimmune vote of 75-65. TAMR leaders expect to issues they expect to revisit. Rep. King disorder, but we don’t know what

6 ASBMBToday NOVEMBER 2003 Organize Texas state legislator Rob Eissler (R-Wood- lands) receives an award on October 5 in Austin from TAMR organizers (L to R) Judy Haley, Melinda Rose, and Beckie McCleery. Eissler was recognized for his efforts on behalf of stem cell research in Texas. causes it. That’s why it’s so important that research continue on all fronts so we had instant credibility when we ues on federal legislation in Washington. we can understand its origin, and learn walked into a legislator’s office. And we The two moms both said they were how to treat and cure it.” had this incredible network. When we self-taught advocates. Judy Haley said, The illness in their children motivated needed to have letters written, calls “Our national organizations helped us both of them to get involved in grass made, or people at the capitol, we understand what was going on at the roots advocacy. Last winter when the could send one e-mail or make a series federal level, and our volunteer lobby- anti-stem cell research legislation was of phone calls and have people here in ist Ellen Arnold and others helped us introduced, Mrs. Haley began seeking Austin to get what we needed very at the state level.” advice from the national office of JDRF, quickly. The legislators don’t pay much Beckie McCleery added, “Ellen which suggested she contact other local attention to one or two people, unless helped us find champions in both par- JDRF chapters in Texas. “That’s how you bring lots of money. But if a lot of ties in the legislature who would take Beckie came in,” she said. The two of constituents call, then we get their our fight forward. Then we could go to them, along with Dr. Bill Rainey, a plastic attention. And that’s what we did.” legislators and tell them that there surgeon and himself a victim of a spinal Unfortunately, many states may be were people in their party supporting cord injury, and Terry Bowers, with the facing similar battles in the next several our position.” She laughed, “The last Texas chapter of the Parkinson’s Action years. As of last spring, 22 state legisla- time I was in the state capitol building Network, “started getting together via tures were considering stem cell legisla- before this year was when I took my telephone and e-mail and we realized tion in some form. The number is only son there on a field trip. Believe me, if I that there were many of us who could expected to grow as a stalemate contin- can do this, anyone can do this.” fight on this issue.” Further contacts led to their joining forces with Ellen Arnold, a state lobbyist in Austin who has a niece with diabetes. “Ellen got in it with her heart,” Judy said, “because she was so touched by how incredibly difficult dia- betes was for her niece. She didn’t want to see some potential cure disappear because of the whim of a legislator who perhaps didn’t understand the issue.” Beckie McCleery got active in JDRF through her husband, but had no idea she was soon to be involved in such a tough legislative struggle. “This fight was probably the most controversial topic having to do with research Texas had ever faced. After the first hearing, I realized that the best thing for us to do was join together and be represented by one strong voice rather than by five or six different voices. And it worked—

NOVEMBER 2003 ASBMBToday 7 Two ASBMB Members Selected to Share 2003 chemistry and it could never have hap- eter Agre, Professor pened as fast as it did without the P in the Department of wonderful resources and collaborators Biological Chemistry at available at Johns Hopkins. This is an Johns Hopkins University honor for the entire Hopkins family.” Medical School, and Rod- “This is a great day for the school of erick MacKinnon, John D. Medicine and the University at large,” Rockefeller Jr. Professor said Edward D. Miller, Dean of the Medical Faculty and CEO of Johns and Howard Hughes Med- Hopkins Medicine. “There are few hap- ical Institute (HHMI) pier occasions to celebrate at an aca- Investigator at Rockefeller demic medical center.” University, will share the “This is a terrific day for Peter and a 2003 Nobel Prize in Chem- tremendous day for the Hopkins com- Dr. Peter Agre istry for discoveries con- munity,” added Chi Dang, M.D., Vice cerning channels in cell Dr. Agre Dean for Research at Johns Hopkins. membranes. The pair, That the body’s cells must contain “The prize is not only a recognition of both medical doctors, were specific channels—aquaporins—for the important discoveries on how honored for discoveries transporting water was suspected as materials are transferred into and out clarifying “how salts (ions) early as the middle of the nineteenth of cells, but it’s also symbolic—in the and water are transported century. However, it was not until case of Peter Agre—of being rewarded 1988 that Dr. Agre succeeded in isolat- out of and into the cells of for a job superbly done with great ing a membrane protein that, a year or depth, without fanfare. This should be the body,” according to the so later, he realized must be the long- an encouragement for the young sci- Royal Swedish Academy of sought-after water channel subse- entists that persistence and dedication Sciences. At the December quently named aquaporin. This will yield the joy of discoveries and 10 Prize Award Ceremony decisive discovery opened the door to occasionally, fringe benefits. It also in Stockholm, the King of a whole series of biochemical, physio- highlights that the prepared mind can Sweden will present the logical and genetic studies of water turn serendipity, as in the case of the Awards. channels in bacteria, plants and mam- discovery of water channels, into a par- The Academy recognized mals. Today, researchers can follow in adigm breaking moment.” Dr. Agre for his labora- detail a water molecule on its way William R. Brody, President of the tory’s 1991 discovery of the through the cell membrane and under- Johns Hopkins University, com- long-sought “channels” stand why only water, not other small mented, “The worldwide Johns Hop- that regulate and facili- molecules or ions, can pass. kins community joins with the School “It is a remarkable honor to receive a tate water molecule trans- of Medicine in congratulating Peter for Nobel Prize, because it not only recog- his laboratory’s great achievement.” port through cell nizes discoveries, but also their useful- Since a 1992 paper in Science by Dr. membranes, a process ness to the advancement of Agre and Hopkins Physiologist Bill essential to all living fundamental science,” said Dr. Agre. Guggino, which documented the dis- organisms. Dr. MacKinnon “It is amazing and gratifying that the covery of the very first water channel was cited for “structural Nobel committee feels our work has protein, 10 more have been found in and mechanistic studies of accomplished that milestone in just 12 mammals, and hundreds more in ion channels.” years. That’s warp speed in molecular plants, bacteria and other forms of life.

8 ASBMBToday NOVEMBER 2003 Nobel Prize in Chemistry In Dr. Agre’s lab alone, aquaporins and within a year had cloned its com- Potassium channels are part of the have been discovered to be part of the plementary DNA. In dramatic experi- apparatus that maintains the normal blood-brain barrier and also associated ments with frogs’ eggs, the scientists ionic balance across the cell mem- with critical water transport in skeletal next proved that the unknown protein brane. In excitable cells, like those in muscle, lung and kidney. Members of was in fact biology’s elusive cellular reg- nerves and muscles, for example, the his lab also have found aquaporins in ulator of water transport. channels help re-establish the electrical the eye and in salivary and tear Although Dr. Agre started his career difference between the inside and out- glands. Researchers around the world in medicine, he gradually shifted to side of the cells after excitation. With- now study aquaporins in many laboratory research so that he could out potassium and sodium channels, species of plants, bacteria and animals, investigate fundamental biological neurons could not generate electrical and have linked aberrant water trans- questions whose answers would have signals and hearts could not beat port to a multitude of human diseases clinical relevance. rhythmically. and conditions. “I am certain that in the future, we HHMI researchers at the University “I am so pleased that Peter has been will be able to capitalize on our under- of California, San Francisco were the recognized for his outstanding work standing of aquaporins to benefit med- first to determine the DNA sequence of on aquaporins,” said Dr. Gerald Hart, icine, biotechnology and even a potassium channel—the Shaker Director of Biological Chemistry, the agriculture,” he says. “We still have channel in fruit flies—in 1987. But much to learn, and the possibilities of even with that information in hand, it “We still have much where aquaporins will take us are took several years for Dr. MacKinnon to learn, and the unlimited.” and his colleagues to figure out which amino acids actually formed the tun- possibilities of Dr. MacKinnon nel through which the ions passed. By where aquaporins In 1998, Dr. MacKinnon and his col- using site-directed mutagenesis— leagues determined the three-dimen- painstakingly altering the protein by will take us are sional structure of a pore that allows one amino acid at a time to determine unlimited.” cells to control their intake of potas- the effects of such changes—the Mac- Dr. Peter Agre sium ions. By determining the struc- Kinnon group eventually identified a ture of the potassium pore, or channel, “signature sequence” of eight amino division housing Dr. Agre’s laboratory. he and his colleagues at Rockefeller acids that were key to the channel’s “He has been part of the Johns Hop- University had function. They also demonstrated that kins family for more than 20 years, solved a riddle potassium channels must consist of and we just couldn’t be prouder.” that has per- four subunits, each one contributing The discovery of aquaporin is an plexed bio- its signature-sequence amino acids to example of luck favoring the well-pre- physicists for form a selectivity filter. pared. Beginning in the mid-1980s, he decades: How “We used mutagenesis for nearly 10 and his colleagues, including techni- does a potas- years to study how the potassium cian Barbara Smith and then post-doc sium channel channel works without getting the Gregory Preston, were searching for admit millions answer we needed,” says Dr. MacKin- proteins that are part of the Rh-factor of potassium non. Finally, though, he and his col- when they happened across an abun- ions per sec- leagues produced large quantities of dant and much smaller protein. The ond, while Dr. Roderick MacKinnon the potassium channel from a bac- researchers pursued the unexpected allowing only one smaller sodium ion terium named Streptomyces lividans. protein visitor—they isolated it and dis- to slip through for every 1,000 potas- Then, they isolated the potassium covered that it was widely expressed— sium ions? Continued on page 19

NOVEMBER 2003 ASBMBToday 9 Life Scientist Salaries Reported he median annual income 12,600 individuals. The results are con- reported in a recent survey of tained in the in-depth, 785-page sur- Chemists Moving T the compensation of life scien- vey report, Compensation of Life tists was $65,000, according to a survey Scientists in the United States of Amer- into Life Sciences conducted by Abbott, Langer & Associ- ica - 2003, available for $375 from With unemployment in chem- ates, Inc., Crete, Illinois, and sponsored Abbott, Langer & Associates, Inc., istry at an all-time high, chemists by ASBMB. The composite highest- Dept. NR, 548 First Street, Crete, IL are increasingly turning to indus- income practitioner in this field (salary 60417 (www.abbott-langer.com). Simi- tries in the life sciences, such as plus cash bonus and/or cash profit shar- lar editions are available for Canada pharmaceuticals, that are not as ing), taking into account the size of the and the United Kingdom. hard-hit by economic woes. organization, is the president with a Income data are reported by region, Speaking at the American Chemi- median income of $120,000. Far toward state, and metropolitan area; type of cal Society Annual Meeting in Sep- the other end of the income spectrum, employer; size of organization; level of tember, President-elect Charles P. laboratory assistants have a median education; length of experience; primary Casey said that recent mergers and annual income of $23,600. area of specialization; primary job activ- acquisitions among chemical and E-mail invitations to participate in ity; level of professional responsibility; petrochemical companies have led the survey were sent to subscribers of industry or service of employer; gender; to downsizing and fewer traditional The Scientist magazine, registrants on age; years since highest degree; level of jobs for chemists. In fact, employ- The Scientist web site who identified supervisory/managerial responsibility; ment among chemists is the weak- themselves as U.S.-based professional and numerous cross-tabs of the variables. est it has been since the ACS started life scientists, members of and sub- Median incomes are highest in phar- consistently measuring it 30 years scribers to the American Institute of maceutical, consulting, and manufactur- ago, he said, so ACS members are Biological Sciences and the American ing firms ($89,500, $87,000, and $82,500 turning to careers in biology and Society for Biochemistry & Molecular respectively); and lowest in primary pharmaceuticals, which appear Biology. An invitation to participate schools ($34,970), secondary schools “vital” enough to absorb “displaced was also printed in The Scientist. Usable ($45,775), and colleges/universities grant- chemists.” responses were received from over ing only 2-3 year degrees ($50,006). ACS surveys show that, in 1990, Median total cash compensation from the survey report just over one quarter of ACS Research Vice Presidents/Directors $ 142,000 chemists under 40 years of age who Research Managers $ 139,000 were employed full-time in manu- Chief Operating Officers $ 129,000 facturing were working in pharma- College/University Department Heads $ 129,000 ceuticals. But by 2000, that figure “Distinguished” Researchers $ 126,000 had risen to almost one half. Professors (12-month appointment) $ 118,000 The ACS President-Elect said that Research Section Heads $ 108,387 this shift in employment among Government Section Heads $ 98,000 chemists does not necessarily mean Laboratory Directors $ 90,000 that chemists and life scientists are now competing for the same jobs, Research Unit Supervisors $ 85,000 since each group does very different Professors (9-10 month appointment) $ 85,000 work. However, he said, the influx Laboratory Managers $ 53,000 of chemists into the world of life sci- Interrnediate Researchers $ 50,250 ences does mean that both sides Assistant Professors (9-10 month appointment) $ 49,713 need to learn from each other and Post-Doctoral Researchers (12-month appointment) $ 36,366 how best to interact, in order to Laboratory Technicians $ 35,000 benefit from the change. Intermediate Research Technicians $ 33,000

10 ASBMBToday NOVEMBER 2003 Undergraduate students proudly display their winnings at the Annual Biomed- ical Research Conference for Minority Students (ABRCMS-www.abrcms.org) held October 15-18 in San Diego, California. ASBMB sponsored prizes for the best oral and poster presentations in the biochemical sciences. Each student received $250.00 and complimentary one-year student membership in ASBMB. from l to r: Dr. Phillip A. Ortiz, Empire State College; Oral presenta- tion winner, Junior, Isaac Kinde, University of Maryland, Baltimore County; Senior poster winner, Jessae Carrington, Chicago State University, Junior poster winner, Juliette Sandifer, Tougaloo College; Sophomore poster winner, Annie Arguello, St. Mary’s University, San Antonio, TX Dr. Phillip A. Ortiz of Empire State College, Chair of the ASBMB Minority Affairs Committee, explains the benefits of student membership and the Undergraduate Affiliate Network at the Society for Advancement of Chicanos and Native Ameri- cans in Science (SACNAS-www.sacnas.org) meeting held in Albuquerque, New Mexico, October 2-5.

Second RGS Protein Colloquium Saturday, April 17, 2004 Renaissance Hotel, Washington, DC 9:00 am - 6:00 pm Chairs: Vadim Arshavsky and David Siderovski

RGS proteins: Past, present, future, David Siderovski, UNC - Chapel Hill Mechanisms of feedback inhibition by RGS protein induction and turnover, Henrik Dohlman, UNC - Chapel Hill RGS protein control of centrosome movement during mitosis in C. elegans embryos, Michael Koelle, Yale U. Role of the RGS domain in G protein-coupled receptor kinase function, Jeffrey Benovic, Thomas Jefferson U. RGS insensitive G proteins as probes of physiological RGS function, Richard Neubig, U. Mich Regulation of vascular smooth muscle relaxation and blood pressure by RGS2, Michael Mendelsohn, Tufts U. Investigation of RGS proteins toward modulation of neurobiological disorders, Kathleen Young, Wyeth Research Functional analysis of RGS proteins in intact cells: Lessons from photoreceptors, Marie Burns, UC-Davis Building RGS protein specificity through its domain composition, Vadim Arshavsky, Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston Registration Deadline: March 31, 2004 Registration information is available online at www.aspet.org/public/meetings. Select Second RGS Colloquium. Or contact Margie Arkin, 301-634-7989, [email protected] Presented by: The Division for Molecular Pharmacology of the American Society for Pharmacology and Experimental Therapeutics. This is a satellite meeting to Experimental Biology 2004. Separate registration is required. Protein Modifications and Turnover Organizer: W. J. Lennarz, Distin- Dr. Chris Kaiser, on the formation of The last three symposia will focus guished Professor and Chair, Department disulfide bonds, and by Dr. Shelley on the very active area of protein of Biochemistry and Cell Biology, State Berger on histone modifications. degradation. Session I will be chaired University of New York at Stony Brook There are many post-translational by Dr. Tom Rapoport and will deal modifications and Dr. Gerald Hart will with protein entering and exiting his meeting will consist of six chair the second symposia which will from the ER. Dr. Tadashi Suzuki will symposia between June 13 focus on post-translational modifica- deal with the question of the fate of T and 16, 2004. The overall tion. He will talk about O-N-acetyl glu- the oligosaccharide chains once mis- theme of the meeting will be an inten- cosamine modifications of proteins. folded proteins are exported out of the sive review of the current state of Dr. Robert Haltiwanger will then dis- ER. Dr. Hidde Ploegh will consider understanding of some of the major cuss the various means by which gly- other aspects of the degradation of modifications carried out either co- cosylation affects signal transduction, misfolded proteins. translationally or post-translationally. and Dr. Rui-Ming Xu will describe the The second session focusing on the This subject will be covered in the first structure of some of the enzymes proteosome, will be chaired by Dr. two sessions. In the last three symposia involved in modification of the struc- Daniel Finley, who will talk about the the processes controlling protein ture of histones. mechanisms that regulate proteosome degradation will be presented. In the The third symposium, to be chaired activity, whereas Dr. Alfred Goldberg figure below some of these processes by Dr. Mark Lehrman, will deal with will talk about the proteosome and the are depicted diagrammatically. protein folding in The ER and will fea- unfolding process. Dr. Peter-Michael Symposium 1: This symposium will ture talks by Dr. Armando Parodi and K1oetzel will discuss antigen processing. be chaired by Dr. Lennarz. who will Dr. Avadhesha Surolia on various All of the symposia will be comple- discuss the complexities of the enzyme aspects of the folding process that mented by talks by scientists who have oligosaccharyl transferase. This meet- involves chaperones and lectin-like been chosen to speak based on their ing will also include presentations by interactions. abstracts.

ASBMB Welcomes New Ph.D.s ASBMB extends its congratulations to these individuals who recently received their Ph.D. degrees. In recognition of their achievement, ASBMB is presenting them with a free one-year membership in the Society. The new Ph.D.s are listed below with the institution from which they received their degree. Steven A. Jacobs University of Virginia Jacob D. Mulligan University of Wisconsin, Madison

12 ASBMBToday NOVEMBER 2003 PROTEIN MODIFICATIONS AND TURNOVER MEETING

Organized by William J. Lennarz SUNY at Stony Brook

Co/Post-translational Degradation of Proteins I Modification of Proteins Protein transport in and out of the endoplasmic N-glycosylation reticulum Chair, William J. Lennarz, SUNY at Stony Brook Chair, Tom Rapoport, Harvard Med. Sch. Disulfide bond formation Cytoplasmic PNGase implicated in proteosome- Chris A. Kaiser, MIT mediated degradation of misfolded glycoproteins Tadashi Suzuki Histone modifications , Univ. of Tokyo Shelley L. Berger, The Wistar Inst. Degradation of misfolded proteins Hidde Ploegh, Harvard Med. Sch.

Post-translational Protein Modifications Degradation of Proteins II Additional Speakers will be Function of addition of O-linked GlcNAc to proteins Regulation of proteosome activity chosen from the abstracts Chair, Gerald W. Hart, Johns Hopkins Univ. Sch. of Chair, Daniel Finley, Harvard Med. Sch. Med. submitted to the ASBMB Proteosome and protein unfolding Protein Modifications and Regulation of signal transduction with glycosylation Alfred Goldberg, Harvard Med. Sch Turnover topic categories. Robert Haltiwanger, SUNY at Stony Brook Proteosome and antigen processing Structure of histone modifying enzymes Peter-Michael Kloetzel, Univ. of Berlin Rui-Ming Xu, Cold Spring Harbor Lab. Travel Awards Available for Undergraduates, Graduates, Degradation of Proteins III Postdoctoral Fellows and Folding in the ER Undergraduate Faculty Transcriptional control and the ubiquitin-proteosome Control of N-glycosylation by the unfolded protein system response Chair, William P. Tansey, Cold Spring Harbor Lab. More Information: Chair, Mark A. Lehrman, Univ. of Texas Ubiqutin and protein degradation ASBMB Meetings Office Southwestern Med. Ctr. Aaron J. Ciechanover, Technion-Israel Inst. for 9650 Rockville Pike The interplay of chaperones, lectins and enzymes in Tech. Bethesda, MD 20814 the ER folding process Tel: 301-634-7145 Armando J. Parodi, Fundacion Instituto Leloir Lysosomal cysteine proteinases as key players in Fax: 301-634-7126 protein degradation Carbohydrate substrate recognition by calreticulin Vito Turk, Josef Stefan Inst., Ljubljana, Slovenia Email: [email protected] and calnexin and its role in protein folding in the ER www.asbmb.org Avadhesha Surolia, Indian Inst. of Sci.

www.asbmb.org/meetings Abstract Deadline: February 4, 2004 Cellular Organization and Dynamics Organizer: Harald Stenmark, Schwartz) will zoom out to investigate the dynamic relation- Norwegian Radium Hospital ship between various cytoplasmic organelles using fluorescently tagged proteins. The functional subcompart- he subdivision of eukaryotic cells into function- mentalization of the nucleus will be investigated in a min- ally separate organelles ensures that complex isymposium on “Sub-nuclear Organization” (Chair: Maria T reactions such as receptor signaling, transciption, Carmo-Fonseca). And how are proteins and lipids trans- RNA processing and translation are compartmentalized. ported between different organelles? This will be discussed This compartmentalization, which is considered crucial in a minisymposium on “Vesicular Trafficking” (Chair: Har- for the development of higher organisms, has historically ald Stenmark). been revealed by several techniques, among which electron Finally, two dramatic examples of changes in cellular microscopy has provided the strongest contribution. While dynamics, those of cell division and programmed cell death, the main functional compartments within a cell have proba- will be highlighted in minisymposia on “Meiosis/mitosis” bly been identified by now, we are still learning more about (Chair: Erich Nigg) and “Apoptosis” (Chair: Suzanne Cory), subcompartments within the nucleus and within the respectively. We are happy that top scientists in their respec- endomembrane system. tive fields have accepted to speak at this meeting, which Moreover, recent technical advances in light microscopy should be of interest for anyone who wants to understand have enabled us to study the organellar and molecular more about the organization and molecular/organellar dynamics in living cells. But how is the subcompartmental- dynamics of the cell, and for those who need the tools to ization of eukaryotic cells maintainted, and how do the bio- learn even more. chemical reactions within each subcompartment contribute to cellular functions and intercellular communication? The meeting on “Cellular Organization and Dynamics” will provide a state of the art view of how the cell is organ- ized and highlight the dynamics of important cellular reac- tions. It will also provide our latest insight into the molecular mechanisms that regulate these processes. Fluorescence microscopy has provided a powerful tool for detecting specific molecules within a cell. Not only can this technique be used for determining the subcellular localization of various gene products—in itself a crucial task in the postgenomic era. Recent improvements of fluo- rescence microscopy technicques, including the use of con- focal laser-scanning microscopes and autofluorescent proteins such as the jellyfish green fluorescent protein (GFP), have paved the way for following specific molecules in living cells. Furthermore, it is now possible to detect protein-protein interactions at the subcellular level using fluorescence resonance energy transfer–a great leap in our efforts to understand how molecular machines work. In the plenary talk of the meeting, Roger Tsien will describe how fluorescence microscopy can be used in ingenious ways to unravel the secrets of the cell. There will also be a minisymposium on “Biosensors” (Chair: Mark Philips), which will feature some of the latest tools to study molecular processes in situ. A minisymposium on “Organelle Visualization” (Chair: Jennifer Lippincott-

14 ASBMBToday NOVEMBER 2003 CELLULAR ORGANIZATION AND DYNAMICS MEETING

Organized by Harald A. Stenmark The Norwegian Radium Hospital

PLENARY LECTURE: Unlocking cell secrets with photons and molecular spies Roger Y. Tsien, HHMI, UCSD

Biosensors Organelle Visualization Visualization of Ras signaling Transport through the Golgi apparatus Chair, Mark R. Philips, New York Univ. Sch. of Chair, Jennifer Lippincott-Schwartz, NICHHD, NIH Med. Characterization of the steps in Visualizing calcium signaling vesicle-membrane fusion Tullio Pozzan, Univ. of Padova, Italy Gary Banker, Oregon Health Science Center Local and global reactions in chemotactic gradient Membrane trafficking and neuronal polarity sensing Sanford Simon, Rockefeller Univ. Peter Devreotes, Johns Hopkins Univ. Sch. of Med. Additional Speakers will be chosen from the Apoptosis Vesicular Trafficking abstracts submitted to Making life and death decisions for cells the ASBMB Cellular Endocytosis in receptor down regulation Chair, Suzanne Cory, The Walter and Eliza Hall Inst. Organization and Chair, Harald A. Stenmark, Norwegian Radium of Med. Res., Melbourne, Australia Dynamics topic Hosp., Oslo categories. The Bcl-2 family and mitochondrial membrane Signal-mediated protein sorting in the endosomal- permeability in apoptosis lysosomal system Don Newmeyer, La Jolla Inst. for Allergy and Juan S. Bonifacino, NICHHD, NIH Immunology Travel Awards Available for Undergraduates, Graduates, Phosphoinositides and membrane traffic in neurons Physiological role of apoptotic DNA degradation Postdoctoral Fellows and Pietro De Camilli, HHMI, Yale Univ. Sch. of Med. Shigekazu Nagata, Osaka Univ. Med. Sch., Japan Undergraduate Faculty Meiosis/Mitosis Sub-Nuclear Organization More Information: The centrosome cycle, chromosome segregation The biogenesis of messenger RNA in the nucleus ASBMB Meetings Office and cell division Chair, Maria Carmo-Fonseca, Instituto de 9650 Rockville Pike Chair, Erich A. Nigg, Max Planck Inst. of Medicina Moleular, Lisboa, Portugal Bethesda, MD 20814 Biochemistry Tel: 301-634-7145 The cell biology of genomes Fax: 301-634-7126 Regulation of the microtubule cytoskeleton Tom Misteli, NCI, NIH Yixian Zheng, HHMI Carnegie Inst. of Washington Email: [email protected] Silencing to gene expression: real-time analysis in www.asbmb.org The role of the synaptonemal complex during male living cells and female meiosis David Spector, Cold Spring Harbor Lab Christer Höög, Karolinska Inst., Stockholm, Sweden

www.asbmb.org/meetings Abstract Deadline: February 4, 2004 Integration of Signaling Mechanisms Organizer: Kjetil will discuss signal pathways that Signaling by adaptor molecules in Taskén, Professor involve small G proteins regulating immune cells and Director, the cellular adhesion. André Veillette, Laboratory of Molecular Biotechnology Signal convergence at the serum Oncology, Montreal Centre of Oslo. response element University of Oslo, Richard Treisman, Cancer Research UK Genetic and Norway London Research Institute Molecular Resolution of Signaling Signalling by Ras-like small GTPases f the more than 30,000 genes Structural basis for regulation of pro- and integrin-mediated cell adhesion in the human genome, over tein phosphatases and protein kinases Johannes Bos, University Medical Center O 20% of encode proteins Chair, David Barford, Institute of Can- Utrecht involved in cellular signaling at various cer Research, London Molecular resolution of structures levels. The large fraction of the Spatiotemporal genome devoted to cellular signaling Organization of of kinases and phosphatases has illustrates the fundamental importance Signaling Events been instrumental in understanding function. The increasing through-put of these processes. Likewise, signaling A concept that has developed over of new structures resolved provides molecules are often perturbed in dis- a little more than a decade is the basis for structural comparisons ease and are major targets for drug compartmentalization of signalling across genomes and across classes of developments. The overview of signal- pathways via anchoring and scaffold- molecules and this opens up for ing molecules provided by completion ing proteins and docking and adaptor structure-based drug design on large of a number of genomes combined molecules, the observation that local classes of enzymes. Similarly high- with a toolbox of new techniques in pools of diffusible messengers are suf- throughput techniques for analysis proteomics and functional genomics ficient for signaling and the idea that of protein-protein interactions and that can address interactions and sub- many down-stream substrates appear genetic resolution of signaling path- strates, now leads to an exponential to have their own, private anchored ways makes it feasible to progress growth in understanding of signaling pool of signalling enzymes and effec- into building of signal networks. Dr. and is taking the field from focus on tors. Chair of this symposium will be Pawson will discuss how modular linear pathways to understanding Dr. Taskén who will discuss specific protein interaction domains that complex and integrated intracellular signalling pathways that are localized interact with other proteins, phos- signaling networks which will be high- to lipid rafts and how the timing of pholipids, nucleic acids and small lighted in this meeting. signalling events proceeds in these molecules contribute to building of membrane microdomains. Dr. Scott regulatory systems such as protein Signal Integration will discuss developments in the field complexes and signal networks. Dr. Control of Cell Death Pathways in of anchoring and scaffolding proteins Emr will discuss mapping of phos- Mammary Epithelial Cells that assemble signal effectors together phoinositide signal pathways by Chair Joan Brugge, Harvard Medical with signal terminators of different genetic systems. School signaling pathways into multiprotein Assembly of cell regulatory systems This symposium will focus on signaling complexes that serve as through protein interactions how integration of signals from a crossroads on the highways of cell sig- Tony Pawson, Mt. Sinai Hospital, number of pathways converge upon naling. Dr. Veillette will go into the Toronto down-stream effectors and cell func- world of signaling by docking and tions such as control of cell death adaptors that provide spatiotemporal Phosphoinositide kinase signaling in pathways by various signal inputs. organization of signaling events. membrane trafficking and receptor Dr. Treisman will discuss the signal The Molecular Archetecture of Signal down-regulation networks that come together and Transduction complexes Scott Emr, UCSD, San Diego regulate gene expression and Dr. Bos John Scott, HHMI and Vollum Institute Continued on page 26

16 ASBMBToday NOVEMBER 2003 INTEGRATION OF SIGNALING MECHANISMS MEETING

Organized by Kjetil Taskén University of Oslo, Norway

Signal Integration Genetic and Molecular Resolution of Signaling Control of cell death pathways in mammary epithelial cells Structural basis for regulation of protein Chair, Joan Brugge, Harvard Med. Sch. phosphatases and protein kinases Chair, David Barford, Inst. of Cancer Res., London Signal convergence at the serum response element Richard Treisman, Cancer Res. UK London Res. Assembly of cell regulatory systems through Inst. protein interactions Tony Pawson, Samuel Lunenfeld Res. Inst., Mt. Signaling by Ras-like small GTPases and integrin- Sinai Hosp. mediated cell adhesion Johannes L. Bos, Univ. Med. Ctr.–Utrecht, The Phosphoinositide kinase signaling in membrane Netherlands trafficking and receptor down-regulation Scott D. Emr, HHMI, UCSD

Additional Speakers will Informatics and Modeling of be chosen from the Signaling Pathways Signal Termination abstracts submitted to the ASBMB Integration Signaling through tyrosine phosphorylation Termination of Protein Kinase C signaling Chair, Tony Hunter, Salk Inst. Chair, Alexandra Newton, UCSD of Signaling Mechanisms topic Cue-Signal-Response analysis of cell decision Scaffold interactions involving arrestin, ERK, categories. processes RACK1, AKAPs and XAP2 confer Douglas A. Lauffenburger, MIT compartmentalized regulation of cAMP signaling by distinct PDE4 phosphodiesterase isoforms Modeling MAPK-cascades – robustness and Miles Houslay, Univ. of Glasgow, UK Travel Awards Available for feedback loops Undergraduates, Graduates, Hanspeter Herzel, Humboldt Univ., Berlin Signal termination by protein phosphatase-1 Postdoctoral Fellows and Mathieu Bollen, Katholieke Univ. Leuven, Belgium Undergraduate Faculty Spatiotemporal Organization of Signaling Events Mechanisms of Cytoskeletal More Information: Signaling cAMP signal pathways in membrane microdomains ASBMB Meetings Office regulate Src kinase signaling Signals that regulate epithelial mesenchymal 9650 Rockville Pike Chair, Kjetil Taskén, Univ. of Oslo, Norway transition and invasion Bethesda, MD 20814 Chair, Morag Park, McGill University Health Centre, The molecular architecture of signal transduction Tel: 301-634-7145 Royal Victoria Hospital, Montreal Fax: 301-634-7126 complexes Email: [email protected] John Scott, HHMI, Vollum Inst. Regulation of cell and neuronal growth cone motility Frank Gertler, MIT www.asbmb.org Signaling by adaptor molecules in immune cells André Veillette, IRCM, Montreal The logic of modular signaling proteins Wendell A. Lim, UCSF

www.asbmb.org/meetings Abstract Deadline: February 4, 2004 MEMBERS IN THE NEWS

Lasker Award Honors Rockefeller University Biochemist for Pioneering Studies of Gene Activation obert G. Roeder, Professor definition of the ton University School of Medicine, he and Chair of the Laboratory first of many hun- showed that these three enzymes rec- R of Biochemistry and Molecu- dreds of DNA- ognize and read the messages encoded lar Biology at Rockefeller University binding regulatory in distinct classes of genes in eukary- and a biochemist whose research has proteins, called otes, organisms whose cells contain led to major advances in understand- activators and DNA in a nucleus: RNA polymerase I ing how human genes are switched on repressors, that converts or transcribes DNA into ribo- and off, is this year’s recipient of the control the rate of somal RNA (rRNA); RNA polymerase II prestigious Albert Lasker Award for gene transcription. Lasker Prize winner transcribes DNA into messenger RNA Robert Roeder Basic Medical Research. Over the last (mRNA); and RNA polymerase III tran- Dr. Roeder, an ASBMB member who decade at Rockefeller University, Dr. scribes DNA into transfer RNA (tRNA). shared the 2002 ASBMB-Merck Award Roeder and his colleagues have identi- Both rRNA and tRNA aid in the pro- for outstanding contributions to fied several coactivators, thereby usher- duction of proteins, while mRNA itself research in biochemistry and molecu- ing in a modern age in biology. He says, provides the recipe for a new protein. lar biology with Stanford University’s “We have uncovered a third layer of This last discovery was particularly Dr. Roger D. Kornberg, says, “We need complexity in the transcription remarkable considering that, at the to understand not only the mecha- process.” His laboratory demonstrated time, the tools of molecular biology nisms underlying normal gene activa- that coactivators can be both ubiqui- had yet to be invented. tion, but to relate these to important tous, monitoring many genes in a vari- In the late 1970s, Dr. Roeder devel- medical problems. As we become ety of cells, or specific to one particular oped cell-free systems that allowed familiar with the fundamentals of how cell type. This latter concept of cell- him and others to study the function genes work, we get closer to under- specificity was first introduced by Dr. of individual genes and transcription- standing diseases like cancer or viral Roeder and his colleagues after they related proteins outside of living cells, infections such as HIV.” demonstrated that the coactivator in effect recreating transcription in a For the last 30 years, Dr. Roeder’s OCA-B, first isolated in his laboratory, test tube in a way that faithfully mim- research has provided more than the was unique to B cells, a type of immune ics the real process in cells. Using this beginnings of an answer to the ques- system cell that makes antibodies. powerful test-tube technique, com- tion of how cells control or regulate “What began to emerge,” says Dr. posed of purified RNA polymerases transcription, and how this process Roeder, “is that these coactivators, like and components extracted from cell breaks down in certain diseases, such the RNA polymerases, are incredibly nuclei, he identified distinct sets of as cancer. In addition to outlining vir- complicated machines.” proteins essential for the individual tually all of what we know today about His pioneering work in transcription RNA polymerases to recognize start the basic principles of transcription began while he was a graduate student sites on specific target genes. and its regulation by proteins in ani- in the laboratory of Dr. William J. Rut- He simultaneously identified the first mal cells, he and his colleagues have ter, also an ASBMB member, at the gene-specific activator, TFIIIA, in eukary- created the model from which scien- University of Washington in the late otes. TFIIIA and similar proteins bind to tists throughout the world continue to 1960s. While working on his own specific DNA sequences and enhance study this basic mechanism of life. independent project, Dr. Roeder identi- the “reading” of corresponding target His research includes: discovery of the fied in animal cells three different RNA genes by the appropriate subset of the enzymes— RNA polymerases—that polymerases, as well as specific loca- general transcription machinery. Repres- directly read out and copy the messages tions within the cell’s nucleus that pro- sors perform the opposite task by encoded in DNA; identification of these vided an early indication of the inhibiting a gene’s activity. enzymes’ associated helper factors, the polymerases’ distinct functions. Hundreds of these transcription acti- general transcription machinery; and In subsequent research at Washing- vators and repressors have subse-

18 ASBMBToday NOVEMBER 2003 MEMBERS IN THE NEWS

quently been identified, and many more are expected for the regulation of genes during such physiological Nobel Prize continued ... processes as cell growth and division, Continued from page 9 sional structures have been solved, pri- hormonal processes, virus infection, channel protein in pure form and fig- marily because it is difficult to amass and tumor growth. ured out how to use it to make well- enough of a given transmembrane pro- “The challenge we now face is ordered crystals, a prerequisite for tein to make crystals large enough to understanding the differential regula- determining a molecule’s structure. study. tion of about 30,000 human genes,” After bombarding the crystals with Dr. MacKinnon hopes that the bac- says Dr. Roeder. x-rays, Dr. MacKinnon and his col- terial potassium channels will be useful leagues were able to deduce that the for screening potential new drugs. Two Current Projects potassium channel is made up of four human potassium channels have Between 1991 and 1996, Dr. Roeder’s identical subunits assembled in the immediate medical importance: KATP, lab discovered the major conduit for shape of an inverted teepee. They which is located in the beta cells of the communication between gene-specific found that the wide end of the teepee pancreas that secrete insulin, and activators and the general transcrip- contains the signature-sequence amino tion machinery in animal cells: the acids, which are arranged to form a “It’s as if nature researchers elaborated the biochemical tunnel into which an ion must fit pre- details of a giant coactivator cisely in order to enter a cell. If an ion settled on one way to (TRAP/SMCC) consisting of about 25 is too large, it cannot fit into the tun- make a potassium different protein chains and referred to nel; if it is too small, it does not enter channel.” as the “the human Mediator” after its the tunnel because it cannot align cor- counterpart in yeast. rectly to the tunnel’s sides. Dr. Roderick MacKinnon Currently, the Roeder laboratory is However, he and his co-workers did homing in on precisely how this mas- not stop with the bacterial ion chan- sive protein complex regulates tran- nel: They also conducted experiments HERG, which helps the ventricles of scription. Many of their projects look that showed that the fly Shaker chan- the heart recharge so they can contract at the interaction between it and spe- nel is similarly shaped. The researchers again. HHMI Investigator Dr. Mark cific activators such as nuclear hor- determined that an exquisitely specific Keating of Children’s Hospital in mone receptors, proteins involved in toxin isolated from scorpion venom Boston has linked mutations in HERG development and homeostasis, and binds to the fly Shaker channel and with a disorder called long QT syn- p53, a protein implicated in at least 60 mammalian potassium channels just drome that can lead to deadly heart percent of human cancers. The as tightly as it does to the bacterial arhythmias. Drugs that regulate the researchers previously revealed that potassium channel. Because scorpion activity of these channels might be thyroid hormone receptor and p53, toxins are known to fit the channels useful as treatments for diabetes and in which both are known to activate sev- they block exactly, like a lock and key, preventing sudden death from long eral genes as part of their normal cellu- this suggests that the bacterial, mam- QT syndrome. But many more potas- lar activity, require separate malian and fly channels share the sium channels are likely to become tar- components of the human Mediator same structure. “It’s as if nature settled gets for drug development in the near to properly function. on one way to make a potassium chan- future. Diseases such as hypertension “More precise knowledge of coacti- nel,” he says. and epilepsy, for example, should be vators could offer the potential to The potassium channel is only one treatable through pharmacological design more specific drugs with fewer of a dozen or so proteins that span the control of potassium channel func- side effects,” says Dr. Roeder. cell membrane whose three-dimen- tioning.

NOVEMBER 2003 ASBMBToday 19 Harvard’s Jack Strominger Named ack L. Strominger, Higgins responders in the early innate immune structures of both Professor of Biochemistry in system response. He discovered around classes of MHC J the Department of Molecular 30 specific enzymes required for the proteins and their and Cellular Biology, Harvard Univer- biosynthesis of bacterial cell walls. As bound peptides. sity, will be the 2004 recipient of the the result of emergence of drug resist- He recently also ASBMB-Merck Award. This Award rec- ant bacteria, many of these are now showed that the ognizes outstanding contributions to under investigation as possible targets recognition of the research in biochemistry and molecu- for new chemotherapeutic agents. He class I MHC pro- lar biology. Recipients over the past showed that the last steps are catalyzed tein, III A-C, has a five years have been Stephen Benkovic by a set of bifunctional transglycosy- different func- Dr. Jack Strominger in 2003, Robert G. Roeder and Robert lase/transpeptidases, the penicillin tion. It is the dominant inhibitory ligand D. Kornberger who shared the Award binding proteins that are inactivated whose recognition regulates the activity in 2002, Avram Hershko and Alexan- by penicilloylation resulting from of human natural killer cells. der J. Varshavsky who shared the enzymatic cleavage of the β-lactam Most recently, the ASBMB-Merck Award in 2001, Robert L. Baldwin in ring. His remarkable 1965 and 1980 awardee has focused on the applica- 2000, and Alexander Rich in 1999. The publications on the penicillin mecha- tion of the knowledge gained to the Award consists of a stipend, plaque, nism were shown this past year to be study of human autoimmune diseases, and transportation and expenses of the correct in even their most detailed as illustrated by many recent papers. recipient and spouse to the 2004 hypotheses.” One of these has the potential for Annual Meeting, at which Dr. Stro- Over the past 30 years, Dr. Stro- developing an important new therapy minger will present a lecture. minger pioneered in the discovery of for multiple sclerosis. In this work he In nominating him for this Award, the structures of both class I and class utilized the biochemical and structural Alexander Rich, William Thompson II human major histocompatibility information derived from his studies Sedgwick Professor of Biophysics, complex antigens and their recogni- of MHC II to design an important new Department of Biology, Massachusetts tion of self and foreign peptides for copolymer for therapy of this disease. Institute of Technology, cited Dr. Stro- presentation to the immune system. In First he realized that a random minger’s pioneering contributions to two truly groundbreaking papers, both amino acid copolymer now used for our understanding of the biochemical published in the Journal of Biological therapy (but with limited effective- basis of molecular recognition in infec- Chemistry, he reported the isolation of ness), Copaxone, had been developed tion and immunity. During his career two classes of histocompatibility pro- without reference to the structure of he made seminal contributions in two tein, and showed that they were HLA-DR2, the MHC II allele with different fields. closely related structurally, differing in which this disease is associated. He “In his early career (1960-1980),” the linkage of their four domains. They then redesigned the copolymer to wrote Dr. Rich, “he elucidated the are the Class I and Class II MHC pro- obtain one that binds many fold better chemical structure of bacterial cell teins (MHC I and MHC II). Only a sin- to HLA- DR2 and showed that the new walls and the mechanism of recogni- gle class had been known previously. copolymer was far more effective than tion of penicillin by bacterial enzymes. In each case the separation of closely Copaxone in the treatment of experi- This field is now having a renaissance related isotypes was accomplished and mental autoimmune encephalomyelitis, based on his early work. The bacterial several MHC I and MHC II proteins the mouse model of the human dis- cell wall components that he identified were crystallized. ease. The new copolymer is now under (and many of whose structures he elu- Dr. Strominger also initiated a collabo- development for clinical trial in the cidated) are now under investigation ration with his Harvard colleague, the human disease. It is an elegant exam- as the ligands for the Toll- like recep- late Dr. Don Wiley, that resulted in the ple of the application of biochemistry tors on dendritic cells, the primary elucidation of the three-dimensional to human therapeutics.

20 ASBMBToday NOVEMBER 2003 to Receive ASBMB-Merck Award In each of the two fields in which he Rich. “His early discoveries are a mile- with a study of the mechanism of worked, Dr. Strominger opened up an stone in microbiology. The later dis- penicillin action. entirely new area of research of great coveries are arguably the most “About 30 years ago he completely importance. A brief examination of the important contribution to the molecu- changed his interests and carried out number of investigators now working lar basis of immune recognition in the critical experiments on the structures in these two fields and the number of past few decades.” of the human major histocompatibil- published papers demonstrates the Said Herbert Tabor, Editor of the ity antigens and their role in the impact of his work. In the case of his- Journal of Biological Chemistry, “I would immune system. He carried out a large tocompatibility proteins, an impres- like to enthusiastically support the number of critical investigations in sively large number of his students and nomination of Dr. Strominger for the this field, including, with Dr. Wiley, postdoctoral fellows have gone on to ASBMB-Merck Award. I have followed the crystallization and three-dimen- make independent seminal contribu- his work closely since we first worked sional study of several MHCI and tions to various aspects of this field and in the same laboratory at NIH about MHCII proteins. He clearly is one of to hold distinguished professorships. 50 years ago. At that time he started the most productive and imaginative “No other biochemist has pioneered his monumental studies on the struc- investigators in the fields of biochem- more broadly in our science” said Dr. ture of bacterial cell walls, starting istry and immunology.”

NOVEMBER 2003 ASBMBToday 21 NIH NEWS

$85 Million Awarded for Research on better understanding of the Human Immunology and Biode- “A particular emphasis of these human immune response to fense. Approximately $85 million cooperative centers will be moving A potential agents of bioterror over four-and-a-half years will sup- new findings about immune system and rapid development of counter- port research at Baylor Research function out of the lab and into clini- measures such as vaccines and thera- Institute, Dallas; Dana-Farber Cancer cal trials,” said NIAID Director pies are among the objectives of a Institute, Boston; Emory University Anthony S. Fauci. “The flexibility of new National Institute of Allergy and School of Medicine, Atlanta; Stan- the program will allow research proj- Infectious Diseases (NIAID) program. ford University School of Medicine; ects to be redirected quickly as new NIAID has named five Cooperative and University of Massachusetts information is generated in the lab and Centers for Translational Research on Medical School, Worcester. the clinic.” NIGMS to Fund Stem Cell Exploration To elucidate the basic biology of NIGMS. “We also want to help the ogy, developmental genetics and tis- stem cells, the National Institute of research community overcome some sue biology to the study of human General Medical Sciences (NIGMS) is of the technological barriers that have embryonic stem cells. The group will funding three Exploratory Centers for prevented biologists from developing establish a core laboratory for main- Human Embryonic Stem Cell stem cells into a powerful model sys- taining and distributing human Research. NIGMS is awarding $2.2 tem for probing health and disease.” embryonic stem cells to the Univer- million for the first year of funding The new awards are: sity of Michigan scientific commu- for the three 3-year awards, which University of Washington, Fred nity, develop research tools to study over their lifetime are expected to Hutchinson Cancer Research Cen- stem cells, and support education total more than $6.3 million. ter: $753,000 for the first year of and training on the use of the cells. A key goal is to train basic scientists to funding to improve methods to WiCell Research Institute in Madi- learn how to work with the finicky cells. culture, maintain, manipulate, dif- son, Wisconsin: $669,000 for the According to NIGMS, many researchers ferentiate and compare the 12 fed- first year of funding to create a cen- have had a difficult time getting stem erally approved human embryonic tral core facility to provide cell tissue cells to thrive in an undifferentiated stem cell lines. The group will also culture support, including media state in the laboratory. The shortage of seek to identify the molecular sig- preparation, quality control and rou- scientists with expertise in stem cell nals that enable stem cells to self- tine chromosomal analysis of cul- research and the lack of molecular tools renew, evaluate methods for tured stem cells. The group will to study stem cells are currently limiting genetically modifying stem cells, examine in detail how stem cells advances in the progress of embryonic and study how stem cells choose make the transition from primitive stem cell research. to become specialized cell types cells to becoming neurons, and study “NIGMS recognizes a critical need such as neurons and heart cells. how certain signals cause stem cells to increase the scientific workforce in University of Michigan Medical to lose their ability to self-renew, as this important area of 21st century School in Ann Arbor: $778,000 for well as how molecules produced by biomedical research,” said Judith H. the first year of funding to apply “feeder cells” support the self- Greenberg, Ph.D., Acting Director of knowledge and expertise in cell biol- renewal process.

22 ASBMBToday NOVEMBER 2003 NIH NEWS

Human Immunity and Biodefense Investigators funded through the information from single immune “One of the key features of these new new program will form a biodefense cells, so that very small tissue and centers will be the high degree of infor- research network with a focus on the blood samples can be tested. Imaging mation-sharing by all the members,” human immune system. technologies will also be developed to noted Daniel Rotrosen, Director of The absence of necessary technolo- allow non-invasive, real-time views of DAIT. “Ultimately, we hope to gies is a significant barrier in human the body as it reacts to vaccine or fully characterize human immune immune function research, according infection, Dr. Quill notes. The responses to disease-causing organisms to Dr. Helen Quill, of NIAID’s Divi- improved techniques could help and develop therapies that strengthen sion of Allergy, Immunology and researchers determine the immune these responses, whether the organisms Transplantation (DAIT). To overcome mechanisms responsible for strong are deliberately released or arise natu- this obstacle, researchers at the coop- versus weak vaccine responses. The rally in the environment. The coopera- erative centers will, among other information will be useful in develop- tive centers will encourage the kind of measures, develop new ways to get ing novel vaccines. synergy needed to meet this goal.”

CHAIR DEPARTMENT OF MICROBIOLOGY Meharry Medical College seeks a nationally recognized individual with a Ph.D. degree, M.D. degree or both to serve as Chairman of the Department of Microbiology. Meharry Medical College has Schools of Medicine, Dentistry, Graduate Studies and Research, and Allied Health Professions. Current funded research in the Department includes, cellular and molecular microbiology, immunology, microbial pathogenesis, and molecular parasitology. The successful candidate will have a distinguished national reputation and a record of scholarly activities, including a strong track record in microbiology and/or immunology research with strong extramural funding. In addition, he or she must have impressive evidence of academic leadership, and must be able to motivate and mentor faculty and staff. He or she must have recognition and expertise in teaching in the field of Microbiology and/or Immunology relevant for education and research in the medical, dental, and graduate schools. Furthermore, the individual should have a vision that sup- ports the mission of Meharry Medical College. In effect, we are seeking an exemplary individual who can lead the department, build a strong research program and provide excellent educational programs. The academic rank for this position will be commensurate with either an associate or full professor level based on qualifications and experience. Applications will be reviewed immediately, and the search process will continue until the position is filled. Please, send full application including Curriculum Vita and a brief statement of interest to: Dr. Samuel Evans Adunyah, c/o Ms. Cassandra Ward, Dean's Office, Meharry Medical College, School of Medicine, 1005 D. B. Todd Boulevard, Nashville, TN 37208.

NOVEMBER 2003 ASBMBToday 23 BIOTECH BUSINESS NEWS

by John D. Thompson, Editor Is Biotechnology Coming to ill Fairfax County in North- is a worldwide communications and GMU’s National Center for Biode- ern Virginia become a transportation hub. The county’s trans- fense will be leading counter-terrorism W Mecca for biotechnology formation as a business and technology research with partners from private business? “Location, location, loca- center can be seen through a few statis- industry. tion” has long been the guiding star tics: The county is home to 4,800 tech- Inova Fairfax Hospital, a tertiary-care for retailers, and it could well prove to nology companies, has been responsible center, has been designated a Top 100 be the key to further boosting the for 40 percent of the job growth in the National Benchmark Hospital. economy for Fairfax and Northern Vir- Washington, D.C., area for the last five The American Type Culture Collec- ginia as a whole. years, and county residents alone tion is the nation’s main repository of As the Fairfax County Economic account for 24% of the income tax col- cell lines for life-science research and Development Authority sees it, when lected in Virginia annually. However, business. you look at a map of the Atlantic Coast now the county hopes to capitalize on Ely Lilly plans a $425 million, states, Northern Virginia is a biotech- the growing application of information 600,000 square foot insulation manu- less gap in the Middle Atlantic. To the technology to biotechnology and bio- facturing plant in Northern Virginia. north, there are concentrations of medical processes. The opportunities are MITRE, a federally funded and biotech business and research centers enhanced by a large and growing array research and development company, is in the Boston, New York, Philadelphia, of bioscience resources in northern Vir- a member of the International Consor- Wilmington, and Baltimore/Washing- ginia and the immediate area. tium for Brain Mapping. ton areas, and then nothing much all The Howard Hughes Medical Insti- Industry organizations encouraging the way down to Research Triangle in tute, one of the world’s top privately- the development of Northern Virginia North Carolina. owned biomedical research centers, is as center of bioscience business include In Northern Virginia, on the other building a $500 million campus at the Virginia Biotechnology Associa- hand, there is a gap. However, county Janelia Farm just minutes away from tion, Bio IT Coalition, and the Bio- officials do not see it is a gap in terms of Fairfax County; Johns Hopkins Univer- MedTech Committee of the Northern the infrastructure—research and educa- sity receives more federal research-and- Virginia Technology Council. tion institutions, a highly educated work- development dollars than any other Virginia Commonwealth Univer- force, plenty of available land, close university in the nation; and NIH, NSF, sity’s Medical College of Virginia has proximity to the federal government and and FDA are among the dozens of fed- established a program with Inova its potential as a source for business and eral research institutions and regulatory Health Systems to train third- and research grants, and a location at the cen- agencies in the Washington, DC area. fourth-year medical students at Inova ter of a worldwide communications and The new Fairfax County BioAccelera- Fairfax Hospital. The 50 residents in transportation hub. According to the Fair- tor, which opened in 2002 as an incuba- healthcare/medicine at Inova Fairfax fax County Economic Development tor for bioscience business serves as a now, will be 100 a year come 2005. Authority (FCEDA), which serves not just focal point and catalyst for growth in the Chantilly Academy, a Fairfax County the county but all of Northern Virginia, life-science area. Its 7,500 square foot high school, has launched a bioinfor- the gap is not a gap but an abundant field complex is located near the Northern matics course. of opportunity to be harvested. Virginia Community College Medical High-end research in biotechnology Fairfax County EDA officials do not Education campus the will open this fall. is just one of the reasons why Fairfax’s see a gap in infrastructure. They note George Mason University (GMU) Thomas Jefferson High School has that Fairfax is home to research and edu- has three bioscience institutes to help been the top school in the National cational institutions, a highly educated educate the biotech workforce of the Merit Scholarship program for 11 of workforce, plenty of available land, is future: the Krasnow Institute, Center the last 12 years. next door to the federal government for Bioresource Development, and Among biotechnology and bioinfor- and its business and research grants, and School of Computational Sciences. mation firms that have found opportu-

24 ASBMBToday NOVEMBER 2003 BIOTECH BUSINESS NEWS

Virginia’s Fairfax County? Gerald L. Gordon, tion was found in Teradata, a data ware- neurs throughout the Washington, DC, President and CEO of house platform common to banking area start or grow their businesses. the Fairfax County and retail but new to life sciences. Now, The University of Virginia and Vir- Economic Develop- ment Authority, says the resulting database is in production ginia Polytechnic Institute (Virginia “We see the bio- and IMC is busily building similar data Tech) share a 105,000-square-foot facil- sciences as one of the warehouses for customers overwhelmed ity in Falls Church and offer under- building blocks to an with gene expression data. graduate and graduate programs in a even more diversified Other major Northern Virginia firms wide range of disciplines. Also in the and stable economy in the biotech and bioinformatics area immediate area is the University of Vir- for Fairfax County. We know that building that sector will be take time, but this is a great are American Medical Labs, Biotraces, ginia’s Darden School of Business and location for biotech companies looking to Cel-Sci, Covance Laboratories, Old Dominion University, which oper- exploit an IT infrastructure, a highly educated FOCUS/MRL, and Quintiles. ates an interactive distance learning workforce, and federal government resources.” Companies such as these benefit program from its Annandale campus. nity in Northern Virginia are from Fairfax County and the adjoining A major factor in providing an edu- Healthtechnomics, Inc., a developer of area’s highly educated and growing cated and skilled workforce is North- computer-based health education mate- workforce. Over 30% of Fairfax resi- ern Virginia Community College rials for such federal agencies as NIH; dents hold a master’s or professional (NVCC), which serves over 60,000 Digital Reasoning which has developed level degree, and almost 60% have a students in credit courses and more analytical software that allows health- bachelor’s degree compared to just 25% than 300,000 in non-credit courses care practitioners to share realtime drug of the total U.S. workforce. This is and this fall is opening, in Springfield, interaction and toxicity data with phar- hardly surprising; the county is a its sixth campus. In 2001, Community maceutical firms and use the resulting national leader in education and Fairfax College Week named NVCC as one of data for clinical trials; HealthRx.com students consistently rank well above the top-ranked community colleges in which provides software products and the national average in SAT scores. the number of associate degrees con- research tools to the healthcare and life The three major universities and ferred in business management, sciences community, SmartBead Tech- community college whose campuses administrative services, and health- nologies, a developer of multiplexed are located in, or immediately adjacent care professions. Those two-year grad- assays and technologies for drug devel- to, Fairfax County have equally uates of NVCC who specialized in opment and diagnostics; and ElCare impressive credits, and not only pro- biotechnology or bioinformatics, but Innovations, a medical device and vide a technically-attuned pool of opted not to go on to a four-year col- development company that focuses on potential employees but also serve as a lege, represent a great resource for emergency rescue devices. valuable resource for needed research. incoming biotech companies, particu- Information Management Consul- George Mason University (GMU) is larly in data mining. tants (IMC), a company headed by home to the first engineering school in Northern Virginia Technology Chair the nation to focus on information Affordable Real Estate and FCEDA Commissioner Sudhakar technology—the School of Information A particular attraction in this era of Shenoy, which developed a new bioin- Technology and Engineering. The uni- soaring prices, is ample office space— formatics application for the Salk Insti- versity’s 24,000 students can choose some 100 million square feet—and tute. Salk Neurologist Carrolee Barlow from over 100 programs leading to highly competitive leasing. At the end and her team, were working on a gene bachelors, masters, or doctoral degrees. of 2001, the average rate for a square expression atlas for the mouse brain GMU’s Mason enterprise Center, part foot of office space in Fairfax County when they were confronted with the of the Northern Virginia Small Business was $28.20 per year, compared to problem of too much data to store and Development Center, offers consulting $47.33 in San Jose/Silicon Valley, $40.06 analyze. With IMC’s assistance the solu- and training services to help entrepre- in Boston, and $32.49 in San Diego.

NOVEMBER 2003 ASBMBToday 25 Integration of Signaling Mechanisms continued ... Continued from page 18 confer compartmentalized regulation part of a number of cell signaling Informatics and of cAMP signalling by distinct PDE4 pathways. Dr. Morag will discuss Modeling of Signaling phosphodiesterase isoforms synergistic action of signaling path- Pathways Miles Houslay, University of Glasgow ways in regulation of invasion and morphogenesis whereas Dr. Gertler Signaling through tyrosine Signal termination by protein will go into how signal regulation of phosphorylation phosphatase-1 cytoskeletal dynamics and remodel- Chair Tony Hunter, Salk Institute Mathieu Bollen, Katholieke Univ. ing of actin is required to coordinate Handling and combination of large Leuven experimental data sets and the use of cell movement, adhesion and shape bioinformatics and biostatistics in sys- Mechanisms of change. Dr. Lim will show how tems biology has facilitated that we Cytoskeletal cytoskeletal regulatory proteins can begin to understand the com- Signaling composed of modular domains may confer multi-input signal integra- plexity of integrated signal inputs, Signals that regulate epithelial tion and participate in complex cel- build models and gain an integrated mesenchymal transition and invasion lular circuits. understanding that go well beyond Chair Morag Park, McGill University Regulation of Cell and Neuronal the summarization of the input data. Health Centre, Montreal Growth Cone Motility Whereas Dr. Hunter will address sig- Cytoskeleton encompasses numer- Frank Gertler, Massachusetts Institute of naling networks that involve tyrosine ous dynamic structures that con- Technology, Cambridge phosphorylation, Dr. Lauffenburger stantly are being remodeled and will talk about analysis of cell deci- reshaped. Furthermore, cytoskeleton The Logic of Modular Signaling sion processes and Dr. Herzel will is subject to regulation by signal Proteins share with us the modeling of stress- inputs as well as being an integral Wendell A. Lim, UCSF, San Francisco signaling pathways. Cue-Signal-Response Analysis of Cell Decision Processes Doug Lauffenburger, Massachusetts Institute of Technology, Cambridge Renew Your 2004 Membership Online Modeling MAPK-Cascades – Robust- ness and Feedback Loops Hanspeter Herzel, Humboldt Univer- ASBMB 2004 dues renewal notices have sity, Berlin been mailed to all members. You can now make payment online at the ASBMB web- Signal Termination site: www.asbmb.org, by clicking on Termination of Protein Kinase C “Renew Now” in the “What’s New” box. Signalling The renewal notice includes your 2004 ASBMB membership card. And Chair Alexandra Newton, UCSD, San don’t forget, your membership includes a free subscription to our Diego monthly magazine, ASBMB Today, plus free subscriptions to JBC Online Equally important as signal initia- and MCP Online. You also receive special member rates for tion, is signal modulation and termi- Biochemistry and Molecular Biology Education, The Journal of Lipid nation by the molecular machinery Research and Trends in Biochemical Sciences, as well as the print versions that limits specific signals both in of JBC and MCP. duration and extension. The speakers in this session will address signal termi- ASBMB members may also register for the Annual Meeting at dis- nation of protein kinase C signaling, of counted rates. In addition, you can order your 2004 edition of the cAMP signaling by phosphodiesterases Annual Review of Biochemistry and of protein phosphorylation by through ASBMB. specific phosphatases. If you have any questions, please email [email protected]. Scaffold interactions involving bar- restin, ERK, RACK1, AKAPs and XAP2

26 ASBMBToday NOVEMBER 2003 Career Opportunities

EXECUTIVE OFFICER interpersonal and administrative skills JOHN W. HEIN POSTDOCTORAL American Society for Biochemistry with a record of achievement and RESEARCH FELLOWSHIP AWARD and Molecular Biology (ASBMB) leadership in management of The Forsyth Institute academic, association or other non- A Member Society of the Federation profit organizations. Experience in The Forsyth Institute is a private, of American Societies for Experimental communication with leaders in the Harvard affiliate, world-renowned for Biology (FASEB) scientific, philanthropic and scientific excellence in oral disease and The ASBMB is a leading publishing communities is desirable. developmental biology. We invite international scientific society Applicants should provide a résumé, applicants for the John W. Hein Research representing over 11,000 research the names of three or more references Fellowship. The fellowship provides scientists, academicians and scientists and a cover letter indicating their in training. The ASBMB seeks an generous salary compensation, benefits, strengths for this position. and infrastructure to develop a research Executive Officer due to the imminent Applications will be reviewed program mentored by a Forsyth retirement of Charles C. Hancock, Jr., beginning November 1, 2003. researcher. Support will be for 2 years following 24 years of outstanding Applications provided as electronic service. attachments are preferred. Please with the possibility of an additional year. The mission of the ASBMB is to email application materials to: Applicants should have a Ph.D., MD, or promote understanding of the [email protected] and mail DDS degree, and be US citizens, molecular nature of life processes. This materials to: ASBMB Executive Officer permanent residents, or holders of J1 or mission is accomplished through: Search, Human Resources, Federation H1 visas with the view to obtaining US • publication of the Journal of Biological of American Societies for Experimental residency. Candidates who develop Chemistry, Molecular & Cellular Biology, 9650 Rockville Pike, Bethesda, innovative and productive research Proteomics, Journal of Lipid Research, Maryland 20814-3998. programs have the potential to become Biochemistry and Molecular Biology Education and its magazine, ASBMB ASBMB is an Equal Opportunity Forsyth faculty members. Applicants Today. Employer. should visit the Forsyth web site • organization of an annual scientific (http://www.forsyth.org) for information meeting and specialized meetings. regarding research activities, and to • science advocacy and POST-DOCTORAL RESEARCH FELLOW identify a potential mentor(s). A cover communication with public and (Job $4096) letter indicating research interest and private agencies. A position is available at the Puget mentor, together with a CV that includes • support of scientific education and Sound Blood Center in Seattle, WA to contact information for 3 referees should training at all levels and promoting study megkaryocyte development be sent to Dr. Margaret Duncan, diversity. and thrombopoiesis. Project will Chairman, JWH Committee, The The Executive Officer is responsible focus on signal transduction in Forsyth Institute, 140 Fenway, Boston, for the management of business affairs hematopoietic cells and genetic MA 02115. Affirmative Action/Equal and implementation of actions studies of inherited platelet disorders. initiated by ASBMB Council. Opportunity Employer. Candidates must have a Ph.D. or Responsibilities include coordination of M.D. degree, a background in Council and other ASBMB meetings, elections, interactions with FASEB and hematopoiesis, genetics, or signal Place your Career other professional societies, transduction, and a valid Visa congressional committees, scientific permitting work in the United States. Ads in ASBMB Today meeting coordination, budgetary and Experience with tissue culture, Recruitment advertising is regulatory aspects of publication and molecular biology techniques, and available in ASBMB Today for $12 contract negotiations. Offices of the protein analysis is desirable. Salary is per line, 10 line minimum. Copy is ASBMB are located on the FASEB in accordance with NIH post-doctoral due by the first of the month prior Campus in Bethesda, Maryland. The pay scale. Qualified applicants should to the issue month. For recruitment advertising information call Executive Officer directs a staff of send their curriculum vitae and the Veronica at FASEB AdNet, 800-433- approximately twenty full-time names of three references to: Human employees resident in the ASBMB 2732 ext. 7791 or 301-634-7791, Resources, Puget Sound Blood Center, Offices. Frequent travel to scientific and email: [email protected] 921 Terry Avenue, Seattle, WA 98104- society-related meetings is expected. Display space is also available for Qualified applicants should have 1256, or email to those desiring greater visibility. excellent communication, [email protected].

NOVEMBER 2003 ASBMBToday 27 Calendar of Scientific Meetings

NOVEMBER 2003 Biophysical Society 48th Annual Meeting Biomedical Information Science and Technology February 14–18 • Baltimore, Maryland Abstract Deadline: October 5, 2003 Initiative (BISTI) 2003 Symposium Early Registration Deadline: December 12, 2003 Digital Biology: The Emerging Paradigm Ph: 301-634-7114; Fx: 301-634-7133 November 6–7 • Natcher Conference Center, NIH, Bethesda, MD Website: http://www.biophysics.org/annmtg/site-index.htm Contact: Saundra Bromberg, Capital Consulting Corporation Ph: 301-468-6004, ext. 406 50th Anniversary Gordon Conference on Isotopes in Email: [email protected]. Biological and Chemical Sciences February 15–20 • Ventura, California Protein Symposium and Joint Meeting of the Chair: David N. Silverman, Vice Chair: Charles L. Perrin Argentinean Biophysical Society (SAB) and the Email: [email protected] Argentinean Society for Research in Biochemistry and Website: http://www.grc.org/programs/2004/isotopes.htm Molecular Biology (SAIB) The 1st Gordon Research Conference on The Biology of November 17-21 • San Carlos de Bariloche, Argentina This meeting is sponsored by: The National Agency for the 14-3-3 Proteins Promotion of Science and Technology (ANPCyT), The National February 22–27 • Ventura, California Research Council of Argentina (CONICET), Fundación Chairs: Haian Fu & David Klein, Vice-Chair: Alastair Aitken Antorchas, Fundación Instituto Leloir, University of Buenos Email: [email protected] Aires, University of Quilmes, and The Protein Society. Website: http://www.grc.org/programs/2004/14-3-3.htm Contact: Prof. José M. Delfino ([email protected]) Prof. Fernando A. Goldbaum ([email protected]) Prof. Gonzalo de Prat Gay ([email protected]) APRIL 2004 Prof. Alejandro J. Vila ([email protected]) Experimental Biology 2004 Fx: (54 11) 4962 5457 Website: http://www.biofisica.dna.uba.ar/pssabsaib April 17–21 • Washington, DC Deadline for Submission of Abstracts: November 12, 2003 Website: http://www.faseb.org/meetings/eb2004/ DECEMBER 2003 American Society for Cell Biology 43rd Annual Meeting Xth International Symposium on Amyloid and Amyloidosis December 13–17 • San Francisco, California Late Abstract Submission/Revision Deadline: October 14, 2003 April 18-22 • Tours, France Ph: 301-347-9300; Fx: 301-347-9310 A transdisciplinary meeting that will Website: http://www.ascb.org/meetings/am2003/main03mtg.htm address basic as well as clinical aspects of this field Deadline for Receipt of Abstracts: December 15th, 2003 Abstracts must be submitted in English and only via the web FEBRUARY 2004 via http://www.colloquium.fr/isaa2004 where you will find all the necessary information for submission. Second International Conference on Ubiquitin, COLLOQUIUM-ISAA2004, 12 rue de la Croix-Faubin Ubiquitin-Like Proteins, and Cancer 75557 PARIS cedex 11 (France); Ph: +33 (0)1 44 64 15 15 February 5-7 • University of Texas M. D. Anderson Cancer Fx: +33 (0)1 44 64 15 16; email: [email protected] Center, Houston To allow for the optimal exchange of ideas, the conference will be limited to 175 attendees, who will be selected based on JUNE 2004 past contributions and/or newly developed interests in this field. In addition to the invited speakers, all attendees are American Society for Biochemistry and Molecular encouraged to present posters and some will be invited to Biology Annual Meeting and 8th IUBMB Conference present them at the podium. June 12–16 • Boston, Massachusetts Due to the limited number of attendees, you are encouraged Contact: Kelly Gull; Ph: 301-634-7145; Fx: 301-634-7126 submit online applications prior to the November 15, 2003 Email: [email protected]; Website: www.asbmb.org/meetings deadline. Contact: Amy Heaton; Ph: 713-745-6826 email: [email protected]; website: http://www.sentrin.org

28 ASBMBToday NOVEMBER 2003 Department Heads Take Note:

JULY 2004 4th ANNUAL CONFERENCE OF FOCIS (Federation of Clinical ASBMB Offers Immunology Societies) July 18-23 • Montréal, Canada Free Membership to Deadlines Abstract submission: January 23, 2004 Travel Award applications (CSI and ICI: November 15, 2003 New Ph.D.s Travel Award applications (FOCIS): January 23, 2004 Early Registration: April 30, 2004; Website: www.immuno2004.org ASBMB is now offering a free one-year Associate membership to all students who AUGUST 2004 have, within the past year, earned a Ph.D. degree in the molecular life sciences or 12th International Conference on Second Messengers related areas. and Phospoproteins ASBMB implemented this program as a August 3–7 • Montreal, Canada way to recognize the significant Contact: [email protected] accomplishment of earning the Ph.D., and to Website: http://www.secondmessengers2004.ca provide new Ph.D.s with something tangible and of economic value. Membership in NOVEMBER 2004 ASBMB brings with it a free subscription to the online versions of the Journal of Biological 4th International Congress on Autoimmunity Chemistry and Molecular and Cellular November 3–7 • Budapest, Hungary Proteomics, as well as subscriptions to The Deadline for Receipt of Abstracts: June 20, 2004 Scientist and the Society’s magazine, ASBMB Contact: 4th International Congress on Autoimmunity Kenes International—Global Congress Organisers and Association Today, discounts on other publications, and a Management Services host of other benefits. 17 Rue du Cendrier, PO Box 1726 The Society is asking department chairs CH-1211 Geneva 1, SWITZERLAND Ph: +41 22 908 0488; Fx: +41 22 732 2850 to provide ASBMB with the names and Email: [email protected] addresses of each new Ph.D. recipient from Website: www.kenes.com/autoim2004 their institutions. Upon receipt of this information, we will write the new Ph.D.s to congratulate them on their accomplishment JULY 2005 and offer the free one-year membership in 30th FEBS Congress — 9th IUBMB Conference, 2005 ASBMB. Names and addresses of the new The Protein World; Proteins and Peptides: Ph.D.s should be sent to: Structure, Function and Organization; Kathie Cullins Science is Fun: A Conference for Your Creativity Membership and Subscriptions Manager July 2–5 • Budapest, Hungary American Society for Biochemistry Contact: Ms. Franciska Morlin, Chemol Travel Congress Dept. & Molecular Biology H-1366 Budapest, P.O.Box 28, Hungary 9650 Rockville Pike Ph:+36-1-266-7032, Fx: +36-1-266-7033 Bethesda, MD 20814 Email: [email protected]; www.febs-iubmb-2005.com Email: [email protected] This is an ongoing project; please advise us whenever a student in your department earns the Ph.D., so that we can make this free membership offer to him or her. ASBMBASBMB Publications...Publications... ImpactingImpactingImpacting BiomedicalBiomedicalBiomedical ScienceScienceScience

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