DECEMBER 2003 www.asbmb.org

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AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY HowHow CellsCells RegulateRegulate thethe

Abstract Deadline: February 4, 2004 UptakeUptake ofof NickelNickel

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WilliamWilliam SmithSmith toto ReceiveReceive ASBMB-AvantiASBMB-Avanti AwardAward PagePage 44 Q: WHAT IS BLACK, WHITE, AND READ ALL OVER?

Editor Ralph A. Bradshaw University of California Irvine

Deputy Editor A.L. Burlingame A: University of California San Francisco

Associate Editors Molecular & Cellular properties of proteins and their Ruedi H. Aebersold Proteomics (MCP), expression through original Institute for Systems Biology published by the high quality research. In Seattle American Society for addition, MCP showcases Biochemistry and emerging technologies used to Patricia C. Babbitt Molecular Biology (ASBMB), actively encourages determine how the presence or absence of proteins University of California researchers to submit original papers in the areas of affects biological responses, and how interaction of San Francisco structural and functional properties of proteins and proteins with germane cellular partners allows them their expression. to function. Steven A. Carr Why submit your research to MCP? VISIBILITY OF YOUR RESEARCH… Millennium Pharmaceuticals Inc. MCP is indexed in Medline, Index Medicus, Google, Cambridge LEGACY OF HIGH EDITORIAL STAN- Yahoo, Altavista, AOL, and MSN; therefore your DARDS… As part of the family of ASBMB research will be seen around the world by more Julio E. Celis publications, MCP adheres to the same high level of researchers than ever before. Institute of Cancer Biology and editorial standards adopted nearly 100 years ago by Danish Center for Human the ASBMB flagship publication and most cited OPEN ACCESS… MCP’s latest online feature, Genome Research journal in biochemistry*, Journal of Biological Papers in Press, provides free, worldwide access to Copenhagen Chemistry (JBC). Consequently, your research com- your research on the day it is accepted for mands attention and earns the respect of your peers. publication. The result… faster publication, and Raymond Deshaies greater exposure for your research. EDITORIAL FOCUS… MCP advances the California Institute of Technology * Based on the ISI Journal Citation Reports® 2002 Edition understanding of the structural and functional Pasadena

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AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY DECEMBER 2003, Volume 2, Issue 9

features 7 2 Bad for Biomedical Research

3 Could Glitazones Be Effective Anti-Cancer Drugs

4 William Smith to Receive ASBMB-Avanti Award

6 James Darnell Receives National Medal of Science

7 It’s the Neighborhood that Matters in ALS 8

ON THE COVER: 8 Biologists’ Spotlight Solves Mysteries

14 How Cells Regulate 10 Molecular Recognition and Catalysis the Uptake of Nickel 12 Future of Education and Professional Development in Molecular Life Sciences

14 Structure of West Nile Virus Solved

17 Pehr Harbury to Receive Schering-Plough Award

departments 14 2 Letters 18 News From the Hill 20 Biotech Business 23 Career Opportunities 24 Calendar

BRONZE AWARD WINNER 2003 LETTERS

ASBMB Today is a monthly publication of The American Society for Biochemistry and Molecular Biology Officers Bad for Biomedical Research Bettie Sue Masters President Judith S. Bond President-elect ne deleterious effect of the cal defenses against presumptive bio- Albert E. Dahlberg Secretary Patriot Act and allied execu- logical terrorist attacks. Kenneth E. Neet Treasurer O tive edicts has not been In addition, some scientists are Thomas Blumenthal Councilor William R. Brinkley Councilor mentioned in recent accounts. It being induced to go overseas to pur- Lila M. Gierasch Councilor involves their chilling influence on sue their research in less draconian Frederick P. Guengerich Councilor biomedical research. environments. William J. Lennarz Councilor Alexandra C. Newton Councilor Some investigators are abandoning While scientific exchange between Merle S. Olson Councilor research with organisms that have nations is to be encouraged, this activ- Peter J. Parker Councilor appeared on a “sensitive” list because ity should not have a negative driver. William L. Smith Councilor of egregiously cumbersome require- The intrusiveness of federal antiterror- Non-Voting Members ments recently instituted for permis- ist activities in these areas undermines George M. Carman sion to acquire and work with such creative efforts to the detriment of the Chair, Meetings Committee John D. Scott agents. The American. Type Culture nation as well as civil liberties. Alexandra C. Newton Collection, a major repository for Julio Celis Co-chairs, 2004 Program Committee many cell types, is refusing to fill Dr. Elliot Schiffmann Marion H. O’Leary orders for certain bacterial cultures Chevy Chase, Maryland J. Ellis Bell because of similar arduous restrictions, 301-496-1465 Co-chairs, Education and Professional Development Committee and a number of scientists are destroy- William R. Brinkley ing “suspect” biological samples. This letter from an ASBMB member Chair, Public Affairs Advisory Committee These actions, ironically, are counter- appeared in the Washington Post, Peter A. Rubenstein Chair, Publications Committee productive to developing immunologi- September 13, 2003. Phillip A. Ortiz Chair, Minority Affairs Committee Herbert Tabor Editor, JBC MEMBERS: Have You Activated Ralph A. Bradshaw Editor, MCP Edward A. Dennis Your FREE Subscription to Editor, JLR

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2 ASBMBToday DECEMBER 2003 Could Glitazones Be Effective Anti-Cancer Drugs? esearchers at Georgetown in fat cell development. They are suggest that drugs University’s Lombardi Com- respectively found in breast cancer tis- that block the R prehensive Cancer Center sue and normal breast tissue. When effects of Cyclin have decoded the step-by-step process PPAR is “turned on” by glitazones, D1 may be useful by which a class of popular anti-dia- tumor growth is inhibited. Conversely, in stopping the betes drugs inhibits cancerous tumor when Cyclin D1 is activated in cells, it conversion of growth. With the discovery of this causes cancer cells to divide uncontrol- normal tissue to molecular chain of events, as reported lably and excessively. malignant tissue. in the September 2003 issue of Molecu- The new study reports that the anti- The discoverer lar and Cellular Biology, the George- tumor effects of the PPAR gamma of the human Dr. Richard Pestell town researchers are now studying receptor are actually controlled by the Cyclin D1 gene, Dr. Andrew Arnold, whether these anti-diabetes drugs, cancer-causing Cyclin D1. In short, too Professor and Director of the Center called glitazones, could one day be much Cyclin D1 trumps the PPAR for Molecular Medicine at the Univer- effective anti-cancer drugs. gamma receptor, turning off its ability sity of Connecticut School of Medi- Glitazones are taken by more than to inhibit tumor growth. cine, agrees with the Georgetown two million people with Type 2 dia- Based on these findings, the George- researchers. betes, and are marketed under the town researchers believe that reduc- “This link between Cyclin D1 and names Avandia and Actos. Glitazones tion in PPAR expression coupled with PPAR gamma biochemical pathways is bind to a particular target on a cell, the increase in Cyclin D1 may repre- fascinating and clearly worthy of further and in diabetics, they work by reduc- sent a key genetic alteration underly- exploration, including the potential for ing insulin resistance at the sites of ing the transition from normal breast yielding new treatment modalities for insulin action in the muscle and liver. tissue to breast cancer. These findings cancer,” said Dr. Arnold. Previous studies have also shown that glitazones also have the ability to George L. Kenyon Elected President of IUBMB inhibit tumor growth. However, until this study no one understood how this George L. Kenyon, Dean and Tom gists in the various process worked. D. Rowe Collegiate Professor of Phar- societies of member- “This study shows for the first time a maceutical Chemistry at the Univer- nations. The mis- direct link between a gene causing sity of Michigan, Ann Arbor, was sion of the IUBMB breast and other cancers and a gene elected the 15th president of the is “to foster and sup- linked to diabetes and the production International Union of Biochemistry port the growth of fat cells,” said ASBMB member and Molecular Biology (IUBMB) at and development of the IUBMB’s 18th General Assembly biochemistry and Richard Pestell, Director of the Lom- Dr. George L. Kenyon bardi Comprehensive Cancer Center. on October 12 in Montreal. molecular biology as “The link between these cellular com- Dr. Kenyon, an ASBMB member, the foundation from which the biomolec- ponents may be a lynchpin in some will serve as IUBMB President-Elect ular sciences derive their basic ideas and cancers—linking some cancers and from 2003 to 2006 and as President techniques in the service of mankind.” metabolism directly. Potentially, we from 2006 to 2009. For the past three In addition to organizing and spon- could be on the way to finding new years, he has been Chair of the U.S. soring various scientific conferences therapeutic leads that would improve National Committee for IUBMB, one and congresses around the world, the both diseases.” of several field-specific national com- IUBMB supports the publication of Dr. Pestell and his colleagues mittees run by the National Research several prominent scientific journals describe a complex relationship Council of the National Academies. including Trends in Biochemical Sci- between a cancer causing gene, Cyclin The IUBMB has members from 71 ences, IUBMB Life, Biochemistry and D1, and a cancer-blocking receptor nations, representing approximately Molecular Biology Education, and Mole- called PPAR gamma, which is involved 100,000 biochemists and molecular biolo- cular Aspects of Medicine.

DECEMBER 2003 ASBMBToday 3 William Smith to Receive 2004 he 2004 ASBMB-Avanti target of was the newly discov- Michigan this year. It was at Michigan Award in Lipids will be pre- ered enzyme synthase. State that Dr. Smith tbegan in earnest T sented to William L. Smith, Only a year earlier had Sir John Vane his research on prostaglandin biosyn- Minor J. Coon Professor and Chair of proposed that aspirin worked by thesis and, in particular, on the enzy- the Department of Biological Chem- directly blocking prostaglandin biosyn- mology of prostaglandin synthase. istry, University of Michigan Medical thesis, and only a few years earlier had Not only was his laboratory one of the School, at the ASBMB Annual Meeting. Bengt Samuelsson established the exis- first to isolate, purify, and characterize The Award recognizes outstanding tence of prostaglandin H2 and its this new enzyme, but he also studied research contributions in the area of biosynthesis from arachidonic acid. the distribution of prostaglandin syn- lipids, and consists of a plaque, a Through the work of Dr. Smith and Dr. thase in different tissues, and its stipend, and transportation and Lands, researchers now had the target broader role in the of expenses to present a lecture at the of all NSAIDs, which ushered in a new , from the release of ASBMB Annual Meeting. Dr. Smith’s stage of pharmacological research. arachidonic acid from the phospho- lecture, is tentatively entitled “Struc- After receiving his Ph.D. in 1971, Dr. lipid pool to the recognition of ture, Function and Regulation of Smith pursued postdoctoral research prostaglandins by receptors. Cyclooxygenases.” in carbohydrate chemistry with Dr. This research led the ASBMB-Avanti Dr. Smith is known as an outstand- Clinton E. Ballou, an ASBMB member, Award recipient into studying the molec- ing experimentalist whose prolific at the University of California, Berke- ular biology and gene regulation of this career has yielded seminal work in the ley. By 1974, he had become a senior enzyme. In 1988, he and Dr. David L. areas of biosynthesis, the scientist at the Mead Johnson Com- DeWitt, an ASBMB member, published physiology of polyunsaturated fatty pany in Indiana. However, he wanted the sequence of prostaglandin synthase, acids, and the action of prostaglandins. to return to academic research, and in derived from its cDNA, in PNAS. This He is one of the acknowledged experts 1975 he was appointed as Assistant achievement not only allowed the subse- in the world on the molecular biology, Professor in the Department of Bio- quent isolation and characterization of biochemistry, and enzymology of the chemistry at Michigan State Univer- the prostaglandin synthase gene, but also prostaglandin synthases, the key sity, where he conducted his research the detailed characterization of the enzymes in prostaglandin biosynthe- until moving to the University of enzyme by site-directed mutagenesis. sis, and the target for non-steroidal anti-inflammatory drugs (NSAIDs). He has made contributions to the broad ASBMB Member Receives AAMC Award for Research field of eicosanoid biochemistry and At its annual meeting last month, ogy. He has studied the genome of the physiology in the past, he continues to the Association of American Medical reovirus and gained insight into the base move the field forward, contributing Colleges presented its Award for Dis- life processes of life-threatening diseases, pioneering research, by bringing tinguished Research in Biomedical Sci- such as AIDS and cancer. together researchers to apply cutting- ences to Aaron Shatkin, Director of the Dr. Shatkin, an ASBMB member, edge approaches to the study of the Center for Advanced Biotechnology whose work demonstrates how viruses biochemistry and enzymology of and Medicine, a joint project of Rut- spread within cells, is considered one prostaglandin biosynthesis. gers University and the University of of the pioneer scientists to bring After receiving his Bachelor’s in Medicine and Dentistry of New Jersey- molecular biology and biochemistry Chemistry at the University of Col- Robert Wood Johnson Medical School, to the field of animal virology. While orado in 1967, Dr. Smith began his Dr. Shatkin, an ASBMB member, at the National Institutes of Health, he graduate studies with Professor William demonstrated how viruses spread within studied the genome of the reovirus E.M. Lands at the University of Michi- cells and is considered one of the pioneer and gained insight into the base life gan. It is there that he was introduced scientists to bring molecular biology and processes of life-threatening diseases, to the emerging field of , biochemistry to the field of animal virol- such as AIDS and cancer. and first established in 1972 that the

4 ASBMBToday DECEMBER 2003 ASBMB-Avanti Award This laid the Michael Malkowski to determine the 15 peer-reviewed papers in such jour- foundation for crystal structures of prostaglandin syn- nals as the Journal of Biological Chem- new ground- thase with fatty acid substrates bound istry, Journal of Clinical Investigation, breaking stud- within the active site. and Science. In addition , he has served ies by Dr. The importance of Dr. Smith’s as an Associate Editor of the JBC and of Smith’s labora- research and the regard in which it is Prostaglandins and other Lipid Mediators. tory, as well as held by others is evidenced in the He has been a recipient of an Ameri- numerous labo- number of invited reviews he has pub- can Heart Association Established Inves- ratories around lished over the last 20 years on tigator Award, two NIH MERIT grants, the world. His eicosanoid biosynthesis. His contribu- the Treadwell Award, and the Abraham Dr. William L. Smith work and the tions in the area of lipids, and more White Distinguished Scientific Achieve- molecular biological reagents that his lab- specifically prostaglandins, cyclooxy- ment Award (1996) from George Wash- oratory created aided in the discovery of genases, and lipid mediators, have ington University, and the Senior prostaglandin synthase-2, a second iso- been called outstanding. His work has Aspirin Award from the Bayer Corpora- form of the enzyme, in 1991. With this been seminal and he uses a variety of tion. He has also served extensively as a discovery, the entire face of prostaglandin approaches from molecular and cell consultant to granting agencies such as physiology and NSAID biology to structural biology. He has a NIH and the American Heart Associa- changed. Most recently, he has collabo- record of publications over the last 30 tion, and to numerous pharmaceutical rated with Dr. Michael Garavito and Dr. years, including in the last five years, and biotech companies.

DECEMBER 2003 ASBMBToday 5 James Darnell Receives National Medal of Science resident Bush announced Dr. Darnell, who heads the university's biology of human cancers including eight winners of the 2002 Laboratory of Molecular Cell Biology, multiple myeloma and head and neck P National Medals of Science, was honored for four decades of work on tumors, Dr. Nurse said. This "promoted the nation's highest honor for lifelong gene regulation. His achievements a flurry of research into the ways cells achievements in science and engineer- include discovering pathways by which receive signals to become and remain ing. The honorees included ASBMB cell receptors signal genes. Rockefeller specialized, to respond to growth fac- member James E. Darnell Jr., Vincent University President , speak- tors and to deal with infection." Astor Professor at Rockefeller University. ing for Dr. Darnell who was abroad, told The National Medal of Science was The Scientist, "These signals are sent in established by Congress in 1959 as a reaction to changes in the cell's external Presidential Award to be given to indi- ASBMB Welcomes environment in the body. As a result, the viduals "deserving of special recogni- genes may express a message for a spe- tion by reason of their outstanding New Ph.D.s cific hormone or other protein, or halt contributions to knowledge in the ASBMB extends its congratulations gene expression or activation," physical, biological, mathematical, or to these individuals who recently In particularly far-reaching findings, engineering sciences." A committee of received their Ph.D. degrees. In Dr. Darnell in the mid-1990s identified 12 scientists and engineers is recognition of their achievement, a cell-signaling route, the JAK-STAT appointed by the President to evaluate ASBMB is presenting them with a pathway, that helped to clarify the nominees for this Award. free one-year membership in the Society. The new Ph.D.s are listed Chairman, Department of Biochemistry below with the institution from which they received their degree. The Medical College of Wisconsin (MCW) invites Bret B. Beyer established scientists with vigorous research programs and strong University of Florida, leadership skills to apply for the position of Chairman of Gainesville Biochemistry. The successful candidate will assume leadership of a Eileen M. Burkart nationally distinguished department with 12 full-time, funded Washington University School investigators who are pursuing high-quality research programs as of Medicine well as contributing to medical and graduate education. Areas of research encompass structural biology, enzymology, biological Bojie Dai oxidation, and cellular and molecular biology. Chinese Academy of Sciences This recruitment is taking place in the context of rapid Marisela DeLeon growth and expansion of the Medical College, and the successful Virginia Commonwealth candidate will play a major role in integrating an expanded University Biochemistry faculty into MCW initiatives in cancer research, Jonathan T. Goldstein human and molecular genetics, cardiovascular research, and University of Wisconsin— neuroscience. Madison MCW offers a dynamic intellectual environment in a Richard D. Kensinger community with an excellent quality of life. Interested applicants should submit a full curriculum vitae and letter of interest to: Penn State University College of Medicine Biochemistry Search Committee, c/o Office of the Dean Medical College of Wisconsin, 8701 Watertown Plank Rd. Shr-Jeng Leu* Milwaukee, WI 53226 University of Illinois at Chicago Questions may also be directed to Dr. Paula Traktman, Jeremy S. Myers* Chairman of the Search Committee, at [email protected]. For Louisiana State University more information, visit the departmental web site at * Candidates with an asterisk were previous http://www.biochem.mcw.edu/home.html. MCW encourages Associate members who met the applications from women and minority candidates. requirements for a free one-year membership. EOE/M/F/D/V

6 ASBMBToday DECEMBER 2003 It’s the Neighborhood that Matters in ALS multi-center effort led by more research, but our hope is that stem study, many of the chimeric, or mixed- researchers at the University cell therapy might be a candidate to res- version, mice were completely disease A of California, San Diego cue support cells and treat ALS patients.” free and most others developed ALS (UCSD) School of Medicine, has deter- Estimated to affect some 30,000 only at a later point in time (with mined in mouse models of amy- Americans, most people are diagnosed extensions of average lifespan of otrophic lateral sclerosis (ALS) that the with ALS between the ages of 40 and between one and six months). Even in nerve cells, or neurons, involved in 70, with 55 being the average age of ALS can be either damaged or saved diagnosis. Half of those diagnosed live “Our hope is that stem from degeneration by neighboring only three to five years after diagnosis, cell therapy might be a non-neuronal cells. When non-neu- while fewer than ten percent survive ronal cells harbor a genetic mutation more than ten years. candidate to rescue associated with ALS they can cause To determine if ALS was caused support cells and treat damage in normal “motor neurons.” directly by defects in the motor neu- ALS patients.” Degeneration of motor neurons in rons themselves, or if other cells were ALS leads to progressive loss of muscle inducing motor neurons to die, the Dr. Lawrence Goldstein control, paralysis and ultimately death. researchers studied mouse models of However, when the neighboring non- ALS with a mutation in the gene super- mice carrying the ALS mutation in all neuronal cells are normal, they can oxide dismutase (SOD1). A fraction of their motor neurons, those with a protect or rescue motor neurons from the inherited form of ALS is caused by higher proportion of normal, or wild- degeneration when the neurons them- the SOD1 mutation. type, non-neuronal cells had reduced selves carry the ALS mutation. Pub- The researchers developed 65 mice motor neuron death. lished in the October 3, 2003 issue of that were mixtures (chimeras) of nor- The research team noted that the the journal Science, the findings impli- mal cells and cells with the ALS-caus- longer survival of mutant motor neu- cate non-neuronal cells in the disease, ing mutant SOD1 gene. Past studies rons surrounded by normal cells indi- suggesting the potential of stem cell have shown that mice consisting of cate that these healthy neighbor cells replacement therapy targeting non- 100 percent mutant SOD1 cells have a protective effect on the dam- neuronal cells as a treatment for ALS. develop ALS. Those transgenic mice aged neurons, slowing the progression “In place of the Herculean task of expressing human SOD1 do not get of ALS even when the nerve cells carry replacing the huge, as much as a the disease, while those expressing the the mutant gene. Conversely, the find- meter-long motor neurons damaged FALS-associated SOD1 do. In the new ings that mice with mutant non-neu- by ALS, it would be easier to replace ronal cells develop symptoms of the some of the surrounding cells with disease even when the neuronal cells normal cells. Based on our findings, do not carry mutant SOD1 “supports this could potentially prevent the the view that damage to adjacent non- degeneration and death of motor neu- neuronal cells by mutant SOD1 is a rons that would otherwise be targeted major contributor to disease.” for premature death,” said ASBMB While the cause-and-effect of this member and senior author Don Cleve- relationship is not known, the land, UCSD Professor of Medicine, researchers speculate that the non-neu- Neurosciences and Cellular and Molec- Elizabeth A. Roberts, UCSD. ronal cells play a vital role in nourish- ular Medicine and member of the Lud- A genetic mosaic mouse in which part of its ing the motor neurons, and scavenging wig Institute for Cancer Research. cells (neurons and non-neurons) are normal and toxins from the cellular environment Co-senior author Lawrence S. B. Gold- part express an ALS-causing mutation in super- of the motor neurons. When damaged stein, UCSD Professor of Cellular and oxide dismutase. The black/brown fur represent with mutant SOD1, it appears that they Molecular Medicine and an HHMI some of the cells that express the SOD1 mutant; fail in this role, contributing to the investigator, added, “We still need to do the white fur comes from normal cells. degeneration of the motor neurons.

DECEMBER 2003 ASBMBToday 7 Biologists’ Spotlight Solves Mysteries of Photosynthesis Completion of the molecular-scale picture of how oxygen-evolving bacteria convert sunlight to chemical energy offers potential new insights into plant, as well as animal, metabolism.

sing high resolution x-ray that we can examine these proteins script are Genji Kurisu, visiting scholar crystallography of integral closely with x-ray crystallography, it from Osaka University, Japan, and U membrane proteins, a team could lead to knowledge about how all Huamin Zhang, associate research sci- of Purdue biologists has determined cells exchange energy with their envi- entist in the Department of Biological the structure of the membrane-bound ronment.” Sciences at Purdue, who made major cytochrome b6f complex, one of three Dr. Cramer also said that the study is contributions to the crystallographic protein complexes that govern photo- an important contribution to the young and biochemical part of the analysis. synthesis. There is an extraordinary field of proteomics research because The report paints a picture of the degree of similarity between cyanobac- there is little data on the important complex motion of electrons and pro- terial and plant photosynthesis. While family of membrane-embedded pro- tons across the bacterium’s cell mem- their work does not immediately sug- teins in the total protein database. brane, the boundary between the cell gest any industrial applications, it does “Membrane proteins are involved in and its surroundings. reveal a wealth of information not a cell’s interactions with its environ- “Plant cell membranes are like the only about a chemical process crucial ment, making them an essential com- two ends of a battery,” said ASBMB to all life on the planet, but also about ponent of metabolism,” he said. member Janet Smith, Professor of how cells handle and distribute energy. “However, they are difficult to crystal- Biological Sciences and the team According to team member Dr. lize for study. This research could clar- member responsible for much of the William Cramer, an ASBMB member, ify our understanding of energy flow structure analysis. “They are positive the study is a great leap forward in the in human cells as well, giving us better on the inside and negative on the understanding of photosynthesis. insight into respiration and the absorp- outside, and they are charged up “Where we once could see merely tion of antioxidants in animal cells.” when solar energy excites electrons the tip of the iceberg, we can now per- The report appeared in the journal from water within the cell. The elec- ceive the entire mechanism of photo- Science’s online edition, Science Express. trons travel into the cell membrane synthesis,” said Cramer, Henry Koffler The first two authors on the manu- via proteins that conduct them just Distinguished Professor of Biological like wires. Of course, because of their Sciences in Purdue’s School of Science. high energy level, the electrons want “Before we found a way to crystallize Examining the to ‘fall back’ like water over a dam, the cytochrome, we had a general pic- membrane proteins has releasing the energy a plant harnesses ture of the photosynthetic process, but to stay alive.” possessed only a fraction of a percent been the challenge for The cell that provided the proteins of the information we now have. Now the research team. for the team’s work was a cyanobac-

8 ASBMBToday DECEMBER 2003 and Metabolism The cytochrome b6f protein complex, which is critical for photosyn- thesis. The eight colors represent the eight protein components of the cytochrome complex; the cylinders are the 26 segments of the com- plex that cross the photosynthetic membrane; the colored rings made of little balls that are embedded in protein are the groups that actu- ally carry the electrons stimulated by light absorbed in photosynthe- sis. (Purdue Department of Biological Sciences illustration/H. Zhang)

terium, a filamentous thermophilic bacterium commonly found in hot springs such as those in Yosemite. While animals do not employ photo- synthesis, their cells do make use of similar proteins for respiratory energy transduction. The similarities could Examining the membrane proteins trying, involving about 100,000 per- lead to a better understanding of our has itself been the challenge for the son-hr, we found a way to crystallize own metabolic processes. research team, which is reaping the ben- this multi-subunit integral membrane “What we see when we examine efits of its breakthrough work with pro- protein last year. Because of access to these proteins is the nature of their tein crystallization. While proteomics high intensity synchrotron radiation at partial similarity,” said Dr. Cramer. specialists have been crystallizing pro- the Advanced Photon Source (Argonne “The differences can now be explored tein molecules for years to obtain their National Lab), it then took less than a more easily.” structure, membrane proteins have year until we were able to look at its proven difficult structure in detail.” because they do The team is hopeful that their method not dissolve in can be applied to other integral mem- water, a crucial brane proteins, which they consider a step in the variety of vast untapped potential. crystallization “If cells were countries, membrane process. proteins would control all the interna- “This has left a tional commerce,” Dr. Cramer said. gap in our knowl- “They are the border guards that regu- edge of mem- late all the energy transfer and material brane proteins, exchange across the boundary which total about between the cell and its environment. 30 percent of If you want to get a drug into a cell Purdue Department of Biological Sciences photo/T. Geders Purdue Department of Biological Sciences photo/T. the proteins in where it can be of use, you have to The Purdue University biologists who determined the structure of the cytochrome protein complex are, from left, Professor Janet Smith, Associ- living things,” Dr. deal with the membrane proteins— ate Research Scientist Huamin Zhang, visiting scholar Genji Kurisu, Cramer said. that’s why they’re so important a sub- and Professor William Cramer. “After a decade of ject to study.”

DECEMBER 2003 ASBMBToday 9 Molecular Recognition and Catalysis Organizer: Jack Dixon, Dean for Scientific Affairs and Professor of Pharmacology, Cellular & Molecular Medicine, Chemistry & Biochemistry, University of California, San Diego

he overall session will focus as applied to biological systems to in metabolic control and their func- on Molecular Recognition examine post-translational modifica- tion in complex biological systems. A T and Catalysis. Specific ses- tion of proteins as well as to examine session on molecular recognition and sions will focus on various aspects of macromolecular complexes involved protein targeting will provide novel Molecular Recognition that takes in cell biology. insights into how protein interac- place between mammalian signal The cytochrome P450's have also tions contribute to epithelial cell transduction pathways and bacterial played a key role in molecular recog- polarity in both Drosophila and and viral pathogens. Other sessions nition. Presentations will focus on mammalian systems. Finally, a ses- will address the issues of cellular sig- the chemistry, recognition and cat- sion on the biophysical tools used in naling pathways involved in cell alytic properties of "nature's versatile molecular interactions will focus on growth as well as cell motility. blowtorch." Catalysis in Health and new methods and instrumentation Another area which will be covered Disease will examine the role of pro- involved in following protein-protein includes the use of mass spectrometry teases in anti-angiogenesis, their roles interactions.

10 ASBMBToday DECEMBER 2003 MOLECULAR RECOGNITION AND CATALYSIS MEETING

Organized by Jack E. Dixon, UCSD

Cytochrome P450’s Practical ITC and its applications in protein-ligand and protein-protein interactions Cytochrome P450, nature’s versatile blowtorch Alan Cooper, Univ. of Glasgow, Scotland Chair, Minor J. Coon, Univ. of Michigan Characterization of p38-MAPKAPK2 interaction by Heme-oxygen enzymology: recognition and SPR and ITC catalysis across a rich functional landscape Mark Labadia, Boehringer Ingelheim Stephen G. Sligar, Univ. of Illinois Pharmaceuticals, Ridgefield, CT Pharmacogenomics of P450: evolutionary, functional, and clinical aspects Pathogens Which Intercept Magnus Ingelman-Sundberg, Karolinska Inst., Mammalian Signal Transduction Stockholm Pathways The biochemical interactions between bacterial Catalysis in Health and Disease pathogens and signal transduction systems Methionine aminopeptidase: target for anti- Chair, Jack E. Dixon, UCSD angiogenesis Molecular recognition in host-pathogen interactions Chair, Ralph A. Bradshaw, UC, Irvine Partho Ghosh, UCSD Defining the role of proteolytic enzymes in complex Additional Speakers will be Control of innate immunity by hepatitis C virus biological systems Michael J. Gale, Univ. of Texas Southwestern chosen from the abstracts Charles S. Craik, UCSF submitted to the ASBMB Role of dipeptidyl peptidase IV in metabolic control Molecular Recognition and Cellular Signaling Mechanisms Nancy Thornberry, Merck Res. Labs., Rahway, NJ Catalysis topic categories. Protein phosphorylation in regulation of protein synthesis and cell growth Molecular Recognition and Chair, Kun-Liang Guan, Univ. of Michigan Travel Awards Available for Protein Targeting Map kinase signaling Undergraduates, Graduates, Protein Interaction domains and epithelial cell Natalie G. Ahn, Univ. of Colorado, Boulder Postdoctoral Fellows and polarity Undergraduate Faculty Chair, Benjamin Margolis, Univ. of Michigan Cross talk between heterodimeric G proteins and Rho GTPases Determinants of planar polarity in Drosophila Silvio Gutkind, NIDCR, NIH Michael Simon, Stanford Univ. More Information: ASBMB Meetings Office Asymmetric cell division in the Drosophila nervous Mass Spectrometry Meets Cell system Biology 9650 Rockville Pike Juergen Knoblich, Res. Inst. of Molecular Bethesda, MD 20814 Pathology, Vienna, Austria Analysis of protein modifications by mass Tel: 301-634-7145 spectrometry Chair, Huilin Zhou, UCSD Fax: 301-634-7126 ARBF/ASBMB Symposium - Role Email: [email protected] of Biophysical Technologies in Proteomic tools for dissecting cellular function www.asbmb.org Molecular Interaction Analysis Brian T. Chait, Rockefeller Univ. Chair, Michael Doyle, Bristol-Myers Squibb The study of macromolecular complexes by Pharmaceutical Res. Inst. quantitative proteomics Jeff Ranish, Inst. for Systems Biology, Seattle, WA Quantitating the Time Component of Protein Interactions David G. Myszka, Univ. of Utah Sch. of Med. www.asbmb.org/meetings Abstract Deadline: February 4, 2004 The Future of Education and Professional Development in the Molecular Life Sciences Organizer: J. Ellis Bell, University of Richmond his meeting, organized by the reach activity in every students educa- and Jessica Bell will focus on Emerging Education and Professional tion. Community building and mentor- Areas in the Molecular Life Sciences- T Development Committee of ing motivated the formation of the first on uses of the internet to address the ASBMB continues the recent trend UAN and will continue to be a motivat- issues in proteomics, genomics and at the annual meeting of including a full ing force for the activities of the com- structural biology and second on com- program of activities aimed more at Edu- mittee in the future. At this meeting it is putational approaches, with a focus on cators: faculty at undergraduate institu- reflected in both the encouragement of bioinformatics, molecular visualization tions and at medical schools. In keeping informal interactions with the speakers and computational chemistry and with the recently launched Undergradu- after the sessions and in several sessions dynamics. After both sessions there ate Affiliates Network (UAN), designed aimed at mentoring young faculty in will be opportunities for informal to create communities among under- teaching institutions or graduate stu- lunchtime discussions with the speak- graduates and undergraduate institution dents and post docs interested in devel- ers from the sessions. These sessions faculty a significant component of the oping careers in teaching institutions. will be complemented by the session meeting will focus on undergraduate On the Tuesday of the meeting there on the new Undergraduate Affiliates education and activities with an open- will be a lunchtime workshop on writ- Network where issues of content in ing Undergraduate Orientation and ing research grants for faculty in prima- introductory courses and assessment of Mixer for both faculty and students. rily undergraduate institutions with a student learning will be addressed With an anticipated increase in under- focus on NIH-AREA and NSF-RUI and together with a presentation on the graduate participation in the Meeting CAREER grant writing where a goal of resources that are available through in general, and the Undergraduate the session will be to help identify men- the new UAN. Of particular interest to Research Poster Competition, this ses- tors for young faculty to assist in educators in the area of biochemistry sion will bring students and faculty research grant writing. This will be fol- and molecular biology will be physical together at the start of the meeting and lowed on Tuesday evening with the chemist and renowned author, Peter will feature the revelation of the six Women Scientists Networking Session Atkins from Oxford University focus- regional winners in the UAN Tee Shirt and Reception. ing on how to bring quantitative sci- Design Competition- meeting attendees Although in previous years there has ence back into introductory courses. will have a chance to vote on the six been more of a focus on how to teach, How to teach is not being ignored at regional finalists to select the ASBMB many of the sessions this year will the meeting. Sessions on Getting UAN Inaugural TeeShirt. Details of the focus on what to teach, both skills and Started with PBL, a workshop chaired regional competitions are to be found content, in keeping with the recently by renowned PBL expert Hal White on the various regional UAN Websites. revised undergraduate curriculum in from the University of Delaware, and A central theme behind the organiza- biochemistry and molecular biology. on Training Medical Students, chaired tion of the sessions will be community The symposium sponsored by the by Susan Frost from the University of building and mentoring, both of stu- Minority Affairs Committee will focus Florida College of Medicine. dents and faculty, and the critical role on content issues as well with a sym- Finally, recognizing that not all of that outreach activities play in these posium titled Obesity and Minority the graduate and post doctoral stu- activities. A symposium Outreach activ- Populationsthat should be of particular dents that we train are going to end up ities in the Education of Undergradu- interest to Medical School educators. in careers in academia or industry, Carl ates, Graduates and Postdocs will focus The symposium The Role of Biophysi- Rhodes, from HHMI has put together a on the practical ways that outreach cal Technologies in Molecular Interac- fascinating session on Preparing for activities can be, and must be, incorpo- tionsponsored in conjunction with Diverse Career Futures involving pre- rated into all levels of our educational ARBF will highlight a variety of bio- sentations from a Science writer, a system and reflects the Education and physical techniques and their uses and patent lawyer, and a government Professional Development Committees bring an important quantitative aspect research administrator, which will goal of seeing education at all levels to the overall discussions. A double illustrate the various pathways to incorporate a strong component of out- symposium co-chaired by Judy Voet careers in these areas.

12 ASBMBToday DECEMBER 2003 THE FUTURE OF EDUCATION AND PROFESSIONAL DEVELOPMENT IN THE MOLECULAR LIFE SCIENCES MEETING

Organizer: J. Ellis Bell, University of Richmond

Emerging Areas in the Molecular ARBF/ASBMB Symposium - Role Life Sciences I: Using the Internet of Biophysical Technologies in Molecular Interaction Analysis Co-chairs, Judith Voet, Swarthmore Col. and Jessica Bell, NIDDK, NIH Chair, Michael Doyle, Bristol-Myers Squibb J. Ellis Bell, Univ. of Richmond Pharmaceutical Res. Inst. Kathy Takayama, Univ. of New South Wales, Australia David G. Myszka, Univ. of Utah Sch. of Med. Judith Voet, Swarthmore Col. Alan Cooper, Univ. of Glasgow, Scotland Paul A. Craig, RIT Mark Labadia, Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT

Also: Outreach Activities in the Education of Undergraduates, Undergraduate Education and the Undergraduate Graduates and PostDocs ASBMB Undergraduate Affiliate Orientation and Mixer Network Chair, Stephen L. Hadjuk, Marine Biological Lab., 8th Annual Woods Hole, MA Co-chairs, Neena Grover, Colorado Col. and Undergraduate Student Neena Grover, Colorado Col. J. Martyn Gunn, Texas A&M Univ. Research Achievement Nancy P. Moreno, Baylor College of Medicine Trevor Anderson, Univ. of Natal, South Africa Award Poster Mary Williams, Univ. of Alabama at Peter Atkins, Oxford Univ., UK Competition J. Martyn Gunn, Texas A&M Univ. Marilee Benore-Parsons, Univ. of Michigan, Dearborn ASBMB Emerging Areas in the Molecular Graduate/Postdoctoral Life Sciences II: Computational Travel Award Approaches in the Future Undergraduate faculty grant Symposium writing workshop and networking Co-chairs, Judith Voet, Swarthmore Col. and Minority Scientists’ Jessica Bell, NIDDK, NIH Co-Chairs, Terry S. Woodin, NSF and J. Ellis Bell, Mixer Minoru Kanahisa, BioInformatics Center, Kyoto Univ. of Richmond Women Scientists’ Univ., Japan Jane S. Richardson, Duke Univ. Med. Sch. Networking Training Medical Students Session/Reception Raelene Lawrence, Chemical Computing Group, Canada Chair, Susan C. Frost, Univ. of Florida Col. of Med. Roger W. Koment, Association of Medical Science Obesity and Minority Populations Educators MaryJo Koroly, Univ. of Florida Col. of Med. Travel Awards Available for Chair, Phillip A. Ortiz, Empire State Col. Wojciech Pawlina, Mayo Clinic Undergraduates, Graduates, Felix Ortiz, New York State Assemblyman, 51st Postdoctoral Fellows and District Desmond G. Hunt, NIDDK/NIH Getting Started with PBL Undergraduate Faculty Betty Monroe Kennedy, Pennington Biomed. Res. Workshop Ctr., Baton Rouge, LA More Information: Chair, Harold B. White, II, Univ. of Delaware Kristie J. Lancaster, New York Univ. ASBMB Meetings Office 9650 Rockville Pike Preparing for Diverse Career BioMolecules Alive: The ASBMB Futures Bethesda, MD 20814 Digital Library Tel: 301-634-7145 Chair, Carl Rhodes, HHMI Fax: 301-634-7126 Chair, Paul A. Craig, RIT Kevin Davis, Editor, Bio-IT World Duane W. Sears, UC, Santa Barbara Email: [email protected] Adriane Antler, Pennie & Edmonds, LLP Frank R. Gorga, Bridgewater State Col. Tony Demsey, Research Administratior, NIH www.asbmb.org www.asbmb.org/meetings Abstract Deadline: February 4, 2004 Purdue Team Solves Structure Of West Nile Virus sing cryoelectron microscopy Rossmann, an ASBMB member, and Dr. and advanced imaging tech- Timothy Baker, has described the struc- U niques, a Purdue University ture of other flaviviruses before. While team has determined the orientation of this is the first time West Nile’s struc- the major surface proteins in a West ture has been described, Dr. Kuhn said Nile viral particle. Because these pro- the group’s past work could assist with teins are instrumental in allowing the science’s understanding of this particu- virus to bind to and invade a host cell, lar viral family. the research could be a step forward in “What we already know from study- combating the deadly mosquito-borne ing other flaviviruses could give us a leg disease. The team’s work appeared in up understanding West Nile’s behav- the October 10, 2003, edition of Science. ior,” he said. “Dengue, for example, has

“We can now clearly understand Purdue Department of Biological Sciences image a very similar structure to West Nile’s, how these proteins interact with one This figure shows a surface-shaded image of but its surface features are sufficiently another,” said Richard J. Kuhn, Profes- the West Nile virus particle produced by Purdue different that comparisons could help sor of Biological Sciences in Purdue’s University biologists using cryoelectron shed light on how West Nile operates.” microscopy. The surface is composed of proteins School of Science and an ASBMB that enable the virus to bind with and invade a While Dr. Kuhn is hopeful that the member. “We can’t cure West Nile yet, host cell. The particle is approximately 50 group’s work will add to the effort to but we can now start thinking about nanometers in diameter, or about 1/1000th of contain the disease, he said much how to interfere with these interac- the width of a human hair. additional work will be required to tions, which could be a key to stop- Adding to the knowledge base is the understand the virus’ life cycle on the ping the infection’s progress.” previous work the group has done with molecular level. As West Nile develops inside a host flaviviruses, the viral family that causes “Our structural map now shows cell, several layers of protein molecules diseases including West Nile, dengue only the general orientation of the pro- assemble themselves around the and yellow fever. The group, which is teins,” he said. “What we need now is genetic material, forming a protective composed of researchers from Kuhn’s to include what you might think of as shell. The outer layer of proteins is lab, as well as the labs of Dr. Michael an ‘inset map’ - an even smaller-scale often arranged in an intricate pattern picture that details the structure of of interlocked molecules that can give each of the three protein varieties that the particle’s surface the appearance of make up the virus particle. Then a lattice. When the mature West Nile researchers will have more insight into virus particle emerges, it is these sur- how the proteins bond with cells and face proteins that interact with each other.” another cell’s surface so the next inva- This closer look represents the next sion cycle can begin. step for Purdue’s structural virology “The West Nile virus is formed from group, which has recently received three protein types,” Dr. Kuhn said. new support from the NIH in the form “After the virus assembles in its host of grants totaling nearly $18 million. cell, these protein molecules fit These grants support basic research on

together like a jigsaw puzzle and form Purdue Department of Biological Sciences image viral infectious diseases, including a well-ordered symmetrical particle. This image shows the orientation of the enve- West Nile. From the structure, we now know, lope protein molecules that compose the surface “We currently have a 17-angstrom essentially, how the major sets of pro- of a West Nile virus particle. The major surface resolution structure,” Dr. Kuhn said. tein molecules interlock with each protein is composed of three domains color- “We hope to use our NIH support to other chemically. Armed with this coded pink, yellow and blue. get down to the 9-angstrom scale or The proteins self-assemble in a host cell, forming knowledge, scientists might now con- a well-organized geometric shape. Knowledge of better, as this would give us details on ceive of ways to interrupt the viral the proteins’ structure could help scientists in the the individual protein molecules as assembly process.” effort to develop antiviral agents. well as other proteins in the virus.”

14 ASBMBToday DECEMBER 2003 How Cells Regulate the Uptake of Nickel

athogenic bacteria such as Helicobacter pylori and cer- P tain Eschericia coli strains require substantial amounts of nickel ions to proliferate in the mostly anaerobic environment of the gas- trointestinal tissues they colonize. For example, for H. pylori to colonize the stomach lining and form peptic ulcers, it must first make the low-pH environment of the stomach habit- able. It does this by producing large amounts of a nickel-containing enzyme called urease. Although there is a significant requirement for nickel in these organ- isms, excess nickel can be toxic to cells by binding non-specifically to biomolecules and catalyzing unwanted chemical reactions. It is clear, therefore, that the quantity of nickel taken up into a cell must be tightly regulated. It has recently been demonstrated that one protein, NikR, is important in several different organisms for regulat- ing various aspects of nickel uptake Transcriptional repressor NikR responds to levels of nickel in the cell. On the cover of the magazine and utilization. NikR has been studied is a surface representation of NikR with “nickels” bound. Photo by Eric Schreiter. most extensively in E. coli, where it has motif used to bind DNA. The nickel understanding of metal uptake and been shown to repress transcription of site in NikR displays an unprece- transport is important for the treat- a specific nickel import complex in the dented Ni-binding mode, as well as ment of these conditions. In the case presence of excess nickel ions, thereby the highest reported affinity for Ni in of H. pylori and urease, blocking shutting down nickel uptake when suf- biology. nickel uptake could be a strategy for ficient amounts are already present in “Understanding how the levels of the prevention or treatment of the cell. trace metals are regulated by cells is ulcers. In order to understand how this an important, emerging area,” says protein converts the signal of excess Dr. Drennan. Recent work in other The material for this article was provided nickel into regulation of gene expres- laboratories has yielded structures by Catherine L. Drennan, Assistant Pro- sion, the Drennan laboratory at the of other metal-dependent tran- fessor, Department of Chemistry, Massa- Massachusetts Institute of Technol- scriptional regulators, and “it will chussetts Institue of Technology. Dr. ogy has determined the first struc- be interesting to compare and con- Drennan was the recipient of the 2003 tures of E. coli NikR by x-ray trast these different structures to ASBMB-Schering-Plough Young Investiga- crystallography. These structures, look for themes of metal regulation tor Award which recognizes outstanding which appear in the October 2003 in biology.” research contributions to biochemistry issue of Nature Structural Biology, dif- Too much metal is not a good and molecular biology by researchers fer from all other metal-dependent thing as metal accumulation can recipient who have no more than 10 transcriptional repressors in the lead to disease states. A molecular years post-doctoral experience.

DECEMBER 2003 ASBMBToday 15 ASBMB Members Elected to Institute of Medicine even ASBMB members were engage in a broad range of studies on Paul L. Modrich, Howard Hughes among 65 new members health policy issues. Medical Institute Investigator and S elected in October to the The ASBMB members newly elected to James B. Duke Professor of Biochem- Institute of Medicine of the National the Institute are: istry, Department of Biochemistry, Academies, which now has a total Henry R. Bourne, Professor of Phar- Duke University Medical Center. active membership to 1,382. macology and Medicine, Department of Leona D. Samson, Ellison American Established in 1970 by the Cellular and Molecular Pharmacology, Cancer Society Research Professor, Pro- National Academy of Sciences, the University of California, San Francisco. fessor of Biological Engineering and Institute OF Medicine has become Michael M. Gottesman, Deputy Toxicology, and Director, Center for recognized as a national resource for Director for Intramural Research, Environmental Health Sciences, Mass- independent, scientifically informed National Institutes of Health. achusetts Institute of Technology. analysis and recommendations on Leroy E. Hood, President and Direc- Keith R. Yamamoto, Professor and issues related to human health. With tor, Institute for Systems Biology. Chair, Department of Cellular and their election, members make a com- Timothy J. Ley, Alan and Edith Wolff Molecular Pharmacology, and Vice mitment to devote a significant Professor of Medicine, Division of Dean for Research, School of Medi- amount of volunteer time as mem- Oncology, School of Medicine, Wash- cine, University of California, San bers of IOM committees, which ington University, St. Louis. Francisco.

A postdoctoral position is available immediately in Dr. Bettie Sue Masters’ laboratory studying the structure-function relationships of the three isoforms of synthase. The laboratory uses a variety of molecular biology and biophysical techniques, including deletion and site-direct- ed mutagenesis, static and rapid reaction spectrophotometry, analytical ultracentrifugation, sur- face plasmon resonance spectroscopy, x-ray crystallography, and EPR, among others, to study these purified enzymes and their interactions with other regulatory proteins. Experience in one or more of these techniques is preferred. All postdoctoral fellow appointments are designated as security sensitive positions.

Interested candidates should send or email their curriculum vitae, a brief statement of experience, and the names of three references to: Bettie Sue Masters, Ph.D. President, American Society for Biochemistry and Molecular Biology Robert A. Welch Distinguished Professor in Chemistry The University of Texas Health Science Center at San Antonio Department of Biochemistry MSC 7760 7703 Floyd Curl Drive San Antonio, TX 78229-3900 FAX: (210) 567-6984 E-mail: [email protected]

The University of Texas Health Science Center at San Antonio is an Equal Employment Opportunity/Affirmative Action Employer

16 ASBMBToday DECEMBER 2003 Pehr Harbury to Receive Schering- Plough Research Institute Award ehr A.B. Harbury, Assistant footprinting proteins, and which has barrel gives reduced TIM function, in Professor of Biochemistry, been applied to unfolding intermedi- agreement with the jigsaw model of P Stanford University School of ates in equilibrium with the native folding according to which specific Medicine will receive the 2004 Scher- TIM structure. packing of the core determines the ing-Plough Research Institute Award. Further development of a theoretical backbone fold. On the other hand, The Award recognizes outstanding approach for predicting protein stabil- their results give poor agreement with research contributions to biochemistry ity given the backbone fold and amino the HP, or oil droplet, model of fold- and molecular biology. The recipient acid sequence. An earlier version has ing. (H = hydrophobic, P = polar, and must have no more than 10 years post- been tested with coiled-coils. the HP sequence determines the back- doctoral experience, and need not be Dr. Harbury’s Ph.D. research with bone fold in this model.) Less than 1 an ASBMB member. The Award consists Peter Kim set the stage for his current in 1010 gene sequences with the HP of a plaque, stipend, and transportation work. In a remarkable paper, they and sequence of wild type TIM gives TIM and expenses to present a lecture at the coworkers first predicted by a theoreti- function. A PNAS commentary on this ASBMB Annual Meeting. In addition, cal approach and then demonstrated study termed it a landmark work. up to $1,000 will be awarded for travel experimentally that peptide helices can A practical method of footprinting to attend a meeting of the recipient’s form a right-handed coiled-coil struc- proteins (the MP AX method) was choice. Recent recipients of the Award ture that has an 11-residue hydropho- developed by Dr. Silverman and Dr. were Catherine Drennan in 2003, John bic repeat (Harbury et al., Science, 1998). Harbury (JBC, 2000). The MP AX D. York in 2002, Stephen P. Bell 2001, To analyze mutationally the folding method uses chemical reaction (alkyla- Xiadong Wang 2000, and in 1999 Kun- roles of residues essential for forming tion) with a cysteine side chain to meas- Liang Guan. the TIM barrel, Silverman, Balakrish- ure the accessibility to solvent of the Dr. Harbury has developed new meth- nan, and Harbury (PNAS, 2001) devel- Cys side chain. Alkylation prevents later ods for characterizing the folding deter- oped a novel method of combinatorial cleavage of the polypeptide backbone in minants and folding behavior especially mutagenesis. The method is based on the unfolded protein by the cysteine- of larger proteins and has used them to mutagenizing gene fragments and cutting reagent NTCB. Peptide cleavage characterize the folding of yeast then diversifying the gene library by is determined by mass spectrometry. In triosephosphate isomerase (TIM), a large reshuffling the mutagenized fragments a valid footprinting method, it is essen- dimeric protein each of whose identical with wild type fragments at varying tial that no more than one site should monomers contains more than 250 ratios. They first identified the con- react per protein molecule because residues. These methods are expected to served residues in a phylogenetic align- chemical reaction can cause local be widely used and speed the develop- ment of 43 unique TIM sequences, and unfolding and protein folding is cooper- ment of proteomics. They are: chose 182 sites for mutational analysis. ative. A misincorporation method is Mutational characterization of the They found that 97 sites are freely used to ensure that no more than one folding roles of individual residues, mutable. Then they characterized the Cys residue is introduced per protein based on combinatorial mutagenesis of ease of mutational replacement of the molecule. Misincorporation is achieved gene fragments and reshuffling them other residues, most of which form with a chemically synthesized misincor- with wild type fragments. specific interactions, such as helix cap- porator tRNA for a specific amino acid A footprinting method which cir- ping. They found that any mutation in such as valine, and they made a few dif- cumvents the previous difficulties of the central hydrophobic core of the ?- Continued on page 22

DECEMBER 2003 ASBMBToday 17 NEWS FROM THE HILL

by Peter Farnham, CAE, ASBMB Public Affairs Officer

Omnibus Bill Likely As Most ’04 Appropriations Stall ore than five weeks into the provoked a testy exchange of letters Administration to HHS to Congress, fiscal year, with most appro- between Regula and ranking minority will continue to thwart any attempt to M priations bills still not signed member David Obey (D-WI), but so far compromise the integrity of scientific into law, a gigantic omnibus appropria- Regula is holding fast to his position. research funded by NIH.” Other scien- tions bill is becoming more and more A dispute in the conference committee tific groups issued similar statements, likely. The bill would include all appro- has also developed over proposed Labor and by early November, most in Con- priations bills not signed into law by Department changes in decades-old rules gress appeared to be distancing them- mid-November. It is very likely that this governing overtime compensation. Sena- selves from the list. will include the Labor/HHS bill (which tor Arlen Specter (R-PA) is working to pre- Nevertheless, the flap highlights the funds the National Institutes of Health) vent the changes, but the White House need for continued vigilance over NIH and the VA/HUD bill (which funds the has vowed to veto the bill over this issue. and the merit review system, and it is National Science Foundation). It is believed that inclusion of the very likely that NIH will continue to Regarding the NIH, both the House Labor/HHS bill in an omnibus would receive criticism and public pressure and Senate approved their versions of make the bill harder to veto. not to fund research in certain sensi- the Labor/HHS bill last summer. In tive areas, mostly those related to sexu- the House bill, NIH would receive NIH Peer Review Under ality and gender issues. a $681 million increase, about 2.5 Attack percent over Fiscal Year 2003. The Somewhat overshadowing the more NSF Appropriations Senate bill is slightly more generous. fundamental conference committee dis- The VA/HUD bill, the parent bill for Approved September 10, this bill agreement over the Labor/HHS bill as a the NSF, is even less farther along than would provide NIH with an addi- whole is a dispute that erupted in Octo- the Labor/HHS bill. The House passed tional $1 billion over last year’s total, ber when a list of almost 200 NIH grants the bill in late July, but the Senate was or about a 3.7 percent increase. having to do mostly with HIV and AIDS, still debating the bill as of early Novem- However, the bill has been stalled in sexuality, and gender-related issues was ber. In the House, NSF is funded at $5.64 a conference committee since Septem- made public. An organization called the billion for FY 2004, a 6.2 percent ber, and there is little indication that it Traditional Values Coalition had put the increase. In the Senate bill, the agency will be approved as a “stand-alone” list together earlier this year. However, receives $5.59 billion, a 5.2 percent bill, thus likely consigning it to inclu- due to a misunderstanding, the list got increase. Although Senate Appropria- sion in the omnibus bill. Several prob- sent to the NIH by a congressional tions Chair Ted Stevens (R-AK) wanted to lems have developed in conference. staffer, creating the impression that complete work on this bill before Veter- When the House approved the bill last Congress was concerned about all 200 ans Day, he has apparently been unable July, not one democrat voted in favor of grants. In fact, Congress had intended to do so; thus, this will also likely end up it. The party’s position was that the bill NIH to review a list of only 10 grants. in an omnibus bill. did not adequately fund health and edu- Nevertheless, the mistake generated The VA/HUD and Labor/HHS bills are cation programs. In response to the lack an enormous amount of concern in the usually the most contentious of the of support from House democrats, biomedical research community, and appropriations bills, and can thus be Labor/HHS subcommittee chairman in a statement released on November 5, expected to be among the last bills Ralph Regula (R-OH) deleted funding for FASEB President Robert Wells strongly signed into law each year. There has all “special projects” in the bill that had defended the NIH merit review system. been repeated failure in recent years to been requested by members who voted He said that “FASEB fervently hopes get them signed into law by the begin- against the bill last July. This decision has that the Federal government, from the ning of the fiscal year (October 1).

18 ASBMBToday 2003 UN Delays Vote on U.S.-Backed Cloning Ban he United Nations on According to the Wall Street Journal, a would have led to a treaty committing November 6 voted to put off survey by the Oakland, California-based all signatory nations to legislation that T for two years a vote on a ban Center for Genetics and Society shows would conform to the treaty terms. A on human cloning offered by Costa that 77 percent of countries do not yet ban would make it much more diffi- Rica with the strong backing of the ban reproductive cloning, including the cult to conduct somatic cell nuclear United States. United States, which is which is cur- transfer (SCNT) research, thus making The UN General Assembly was pre- rently seen as unlikely to approve it harder to find cures for various pared to approve with near unanimity human cloning. The survey found that intractable genetic illnesses that SCNT a ban on human cloning to produce a only 16 percent of nations have banned might address. child. However, a sticking point in get- cloning for medical research. Biomedical science groups around ting such an agreement was the United The UN ban, had it been approved, the world expressed relief at the two- States’ position that cloning for would not have the force of law; but year delay. research be included in the ban. The U.S. was the sole industrialized nation supporting an all-inclusive ban. NIH Establishes Rare Diseases One proposal, sponsored by Costa Rica and strongly backed by the United States and at least 63 other cosponsors, Clinical Research Network mostly developing nations, called for a To address the challenges inherent Rare Diseases Clinical ban on all types of human embryo in diagnosing and treating rare dis- Research Centers: cloning. An alternate proposal, intro- eases, NIH has established the Rare Dis- Baylor College of Medicine, Houston, Rare duced by Belgium and supported by eases Clinical Research Network. With Disease Clinical Research Center for New France, Germany, and more than 20 $51 million in grant funding over five Therapies and New Diagnostics. other nations, called for a reproductive years, the network will consist of seven Boston University School of Medicine, cloning ban only. Rare Diseases Clinical Research Centers Boston, Vasculitis Clinical Research However, during the November 6 and a Data and Technology Coordinat- Network. Children’s Hospital Medical Center, debate, a coalition of Islamic nations led ing Center. Cincinnati, Rare Lung Diseases Clinical by Iran offered a proposal that put off a Approximately 25 million people in Research Network. vote on such a ban for two years, which the United States are affected by an esti- Children’s National Medical Center, Wash- won by a single vote. Iran’s Royan Insti- mated 6,000 rare diseases or conditions. ington, DC, Rare Diseases Clinical tute, a government-funded fertility cen- Diseases to be studied in the centers Research Center for Urea Cycle Disor- ter in Tehran, recently announced that include: urea cycle disorders; Angelman’s ders. it had created embryonic stem cells syndrome; Prader-Willi syndrome; Rett The Cleveland Clinic Foundation, Cleve- from an embryo, making Iran the first syndrome; periodic paralysis; non-dys- land, Bone Marrow Failure Clinical Middle Eastern country to do so. trophic myotonic disorders; episodic Research Center. According to a professor of religion ataxia; aplastic anemia; paroxysmal noc- University of Rochester, Rochester, New quoted by the Washington Post in a turnal hemoglobinuria; single lineage York, Nervous System Channelopathies story about the UN vote, Islam does cytopenias, including granular lympho- Pathogenesis and Treatment. Weill Medical College of Cornell not view an embryo as a human being cyte leukemia, pure red cell aplasia, and University, New York City, The Natural and thus Islamic states tend to support myelodysplastic syndromes; vasculitis History of Rare Genetic Steroid somatic cell nuclear transfer (SCNT). disorders; inborn defects in steroid hor- Disorders. Some politically powerful Christian mone pathways; alpha-1 antitrypsin H. Lee Moffitt Cancer Center and Research groups in the United States and abroad deficiency; lymphangioleiomyomatosis; Institute, University of South Florida, have been pursuing a UN ban on pulmonary alveolar proteinosis; and Tampa, The Data and Technology cloning for several years. hereditary idiopathic pulmonary fibrosis. Coordinating Center.

DECEMBER 2003 ASBMBToday 19 BIOTECH BUSINESS NEWS

by John D. Thompson, Editor

Germany Pumps Extra Funding into Biotech Firms Researchers and biotechnology firms outfits founded in Germany during nology prizewinners, who will receive have given a qualified cheer in the recent boom are to struggling to a total of 5.5 million ($6.5 million) response to the recent announcement find venture capital to fund their drug for research and company startups. by the German research ministry that research and development programs. Noting that 10 young German it is committed to “It is very good news,” said Rüdiger researchers who had left the country At last month’s Biotechnology Days Marquardt, director of biotechnology were among the winners, she said that in Leipzig, Federal Minister of Educa- at the German Society for Chemical the award was helping to tackle the tion and Research Edelgard Bulmahn Engineering and Biotechnology, an growing problem of recruiting and announced a commitment to spend- association that represents German maintaining domestic biotechnology ing an extra 100 million ($117 mil- biotechnological companies and researchers. lion)on the sector in the next four researchers. “The injection of funds The German government has allo- years, with the money being directed will help promising companies which cated 480 million $5.6 million to to small- and medium-sized biotech have not yet reached the critical mass biotechnology in 2003. companies. She said that the govern- need to attract venture capital or ment would also extend its coopera- which do not have products on the tion with financiers in a bid to secure market yet, “ he told The Scientist. Scripps to Open an extra 1.7 billion, almost $2 billion) Even companies that have been suc- in venture capital for technology com- cessful in raising capital said that they Florida Branch panies over the next five years. welcome the government’s initiative. La Jolla, California-based Scripps Germany, with some 360 biotech “Extra funding will allow us speed Research Institute has announced companies, is the biotechnology leader up our drug development capabilities,” plans to open an East Coast facility in in Europe and the increased public Giulio Superti-Furga, vice president of Florida’s Palm Beach. The new research investment is intended to consolidate research at Cellzome, a Heidelberg- center, a 364,000–square-foot facility the country’s competitive advantage in based biotech company employing a is scheduled to open in 2006 at an a sector expected to grow substantially hundred people, told The Scientist. expected cost of $140 million. in the coming decades. The boost in During the Leipzig meeting, Minister According to Scripps spokesman funding comes at a time when many Bulmahn also announced 43 biotech- Keith McKeown, the expansion to the East Coast came in response to a “very attractive proposal” from Florida Gov- Genentech, Xoma Get OK for New Psoriasis Drug ernor Jeb Bush, who has asked the South San Francisco biotechnol- treatments such as methotrexate state legislature for $310 million jump ogy giant Genentech Inc. and its and cyclosporine can someimes start the new facility. The interim labs Berkeley partner Xoma Ltd. have damage the liver or kidneys. Rap- as well as the permanent facility with won Food and Drug Administration tiva was cleared for marketing to 100 acres or more of land will all be approval for their drug Raptiva as a adults with moderate to severe pso- provided by Palm Beach County. remedy for the debilitating skin dis- riasis, a market Genenetch esti- Regarding plans for research at the order psoriasis. mates at about 500,000 people. new site, McKeown told The Scientist, “If Raptiva is one of a new class of Analysts estimate that Raptiva there’s anything that would be different biotech-era drugs called biologics could eventually bring in $500 mil- about what we do, it’s that there might that aim to make treatment safer lion per year for Genentech and be a bit more emphasis on drug devel- and more effective for patients Xoma. Genentech set a wholesale opment, because that is what Governor who suffer from the painful skin price that translates to a per-patient Bush is interested in doing in Florida— scaling and irritation. Current cost of about $14,000 per year. jumpstarting the biomedical, biotech- nology, and pharmaceutical industries.”

20 ASBMBToday DECEMBER 2003 BIOTECH BUSINESS NEWS

Science Survey Ranks Top Biopharma Employers Genentech, Inc. and Johnson & John- Ranked in the top 20 slots in the survey were: son earned top honors in a ranking of 1. Genentech, Inc., South San 10. Genzyme Corporation, biopharmaceutical employers in a sur- Francisco, CA Cambridge, MA vey commissioned by the journal 2. Johnson & Johnson, New 11. Biogen, Inc., Cambridge, MA Science. Survey responses were analyzed Brunswick, NJ 12. Abbott Laboratories, Abbott Park, IL by Hughes Research Worldwide, which 3. Amgen, Inc., Thousand Oaks, CA 13. Aventis, Strasbourg, France used a mathematical process to assign a 4. Pfizer, Inc., New York, NY 14. GlaxoSmithKline, London, United unique score to rate the employer repu- 5. Merck & Co., Inc., Whitehouse Kingdom tation of some 323 companies, taking Station, NJ 15. Chiron Corp., Emeryville, CA into account 42 specific characteristics 6. AstraZeneca PLC, London, United 16. Roche, Basel, Switzerland or attributes. Kingdom 17. Wyeth Pharmaceuticals, Genentech Inc. and Johnson & John- 7. Eli Lilly and Company, Collegeville, PA son earned the Number One and Num- Indianapolis, IN 18. Schering-Plough Corp., Kenilworth, NJ ber Two spots on the list, respectively, 8. Novartis AG, Basel, Switzerland 19. Bayer Healthcare, Bayer AG, meaning that they were in the “first 9. Millennium Pharmaceuticals, Inc., Leverkusen, Germany tier” of companies, with rankings of 98 Cambridge, MA 20. Bristol-Myers Squibb, New York, NY to 100. Genentech Inc. was described as offering a research-driven environ- ment and quality management, while Feds Need to “Get on Top” of R&D Enterprise Changes treating employees with respect. John- The Office of Science and Technology stock, a former White House Office of son & Johnson also was described as Policy (OSTP) and the Officie of Man- Science and Technology associate direc- research-driven, with a clear vision of agement and Budget (OMB) need to tor for science, who spoke last month at where the firm is heading and a culture “get on top of” the changing nature of a forum on Research Business Models of respect for employees. research, according to Arthur Bienen- hosted by the Lawrence Berkeley National Laboratory. OSTP and the White House Office of Cyrospace, University of Houston Management and Budget need to take responsibility for seeing trans-agency Sign Commercialization Agreement regulations are implemented evenly, common business practices are adopted Cyrospace Inc. and the University Property Management, said “Our and the administrative burden abated, of Houston have signed an agree- principal goal is to foster research and he said. Moreover, the federal govern- ment in which the company will scholarship. The effective transfer of ment should be paying for such neces- license and commercialize inven- university-wide technology to indus- sities as institutional review boards and tions and technologies created by try contributes to that goal. Cyrospace shared instrumentation, he charged. the faculty, staff and students of the has developed strong commercial Dr. Bienenstock, an OSTP official dur- university. According to the agree- alliances with world-renowned inno- ing the Clinton Administration and ment, Cyrospace will assist UH in vators, as well as educational and now Vice Provost and Dean of Research realizing the commercial potential research institutions. University of and Graduate Policy at Stanford Uni- of its advanced technologies in the Houston joins a select group of organ- versity, called on OMB to allow admin- marketplace. izations benefiting from experience istrative costs as direct funding on Arthur Vailas, the University’s Vice and expertise that Cyrospace con- grants, and stop shifting more and President for Research and Intellectual tributes to such relationships.” more of the cost of doing federally- funded research to the universities.

DECEMBER 2003 ASBMBToday 21 UCLA Receives $500,000 Bristol-Myers Squibb Unrestricted Cardiovascular Research Grant ristol-Myers Squibb has Our strategy is to simultaneously study artery disease, such as hypercholes- awarded a five-year $500,000 both human subjects and mouse ani- terolemia and hypertension, are sys- B Unrestricted Cardiovascular mal models. A better understanding of temic. But our recent studies emphasize Research Grant to the University of Cal- the genetic and environmental factors that a major genetic component in dis- ifornia, Los Angeles (UCLA). ASBMB contributing to this disease will have ease susceptibility involves cellular member Aldons J. Lusis, Professor in the considerable implications for individu- interactions of the vessel wall. We have Departments of Medicine; Microbiology alized therapy and risk assessment.” recently mapped two genes influencing and Molecular Genetics; Microbiology Dr. Lusis said a major area of his cellular functions that can almost com- and Immunology, and Human Genetics research interest has been to character- pletely block atherosclerosis in a hyper- at UCLA, will supervise and serve as ize genetic factors acting at the level of lipidemic mouse model. Knowledge of principal investigator of the grant. the vessel wall, particularly factors that these genes may allow the develop- Simeon Taylor, Vice President of Car- affect oxidation and inflammation. ment of new therapies that compli- diovascular and Metabolics Drug Discov- “Thus far, all of the risk factors that ment those that target high cholesterol ery at the Bristol-Myers Squibb have been identified for coronary and blood pressure.” Pharmaceutical Research Institute in Hopewell, New Jersey, said, “Dr. Lusis is an international leader in the use of the continued mouse model to identify and characterize Schering-Plough ... individual genetic factors for cardiovascu- Continued from page 17 hydrogen exchange method cannot be lar and related diseases. Using mouse ferent misincorporator tRNAs in order used with TIM because of its large size models developed for particular genetic to achieve Cys introduction at many and the requirement for NMR analysis. backgrounds, he and his colleagues have sites. In addition to controls testing the Dr. Harbury is developing a theoreti- developed strains that exhibit such traits validity of the method, this paper con- cal framework that will be used to pre- as diabetes, obesity, hypertension and sus- tains proof that MP AX correctly maps dict amino acid sequences that can ceptibility to atherosclerosis. They are the site of complex formation between form stable TIM-barrel structures. His now also studying the genetic basis of TIM and an antibody, when an anti- algorithm incorporates both polar and atherosclerosis in human families. We are genic determinant is introduced into nonpolar interactions. This paper intro- very pleased to support this important the TIM sequence. duces negative design for preventing work, which should greatly enhance our In a following paper, the two (JMB, the formation of unwanted products, in understanding of the biology of the 2002) apply the MP AX method to deter- addition to positive design for forming processes involved in the development of mining the unfolding pathway of TIM. the desired product. Havranek and Har- the disease and guide the development of The principle is the same as that of bury (NSB, 2003) test the ability of the new genomics-based therapies.” native-state hydrogen-exchange: rare algorithm to predict specific interaction “This unrestricted funding will folding intermediates in equilibrium when helix-forming peptides that greatly help support our studies on the with the native form can be detected by should form a specific coiled-coil het- genetics of atherosclerosis,” said Dr. the high reactivity of groups in the fold- erodimer must compete against a back- Lusis. “Atherosclerosis is a disease of ing intermediate. A Cys side chain that is ground of forming homodimeric the large arteries that is the cause of buried in the native form of TIM but sol- coiled-coils. In this work their algorithm heart disease and stroke and is respon- vent-exposed in a folding intermediate does an excellent job of predicting spe- sible for more than half of all death becomes highly reactive in the folding cific interaction and is quite successful and disability in the Western world. intermediate. They identified and char- in predicting the actual stabilities of the Common forms of the disease have a acterized three cooperatively unfolding coiled-coil products. They identify three polygenic basis, with mixed contribu- subdomains of TIM and proposed a plau- new specificity motifs not seen previ- tions from major genes, modifier sible unfolding pathway. One of the ously in coiled-coil studies. They test genes, and gene-gene and gene-envi- three subdomains is of the same type the algorithm with the well-studied ronment interactions. As yet, this com- found earlier in folding studies of 4 other coiled-coil system before applying it to plex architecture is poorly understood. TIM-barrel type proteins. The native-state the design of new TIM barrels.

22 ASBMBToday DECEMBER 2003 Career Opportunities

OREGON UNIVERSITY laboratory, for our newly developed JOHN W. HEIN POSTDOCTORAL biochemistry major. Other courses Graduate Study in Environmental & RESEARCH FELLOWSHIP AWARD may include an upper-level course in The Forsyth Institute Biomolecular Systems the area of expertise, a course for non- The Department of Environmental science majors, an interdisciplinary The Forsyth Institute is a private, and Biomolecular Systems at the OGI social impact of science course, or Harvard affiliate, world-renowned for School of Science & Engineering, Ore- involvement in the general chemistry scientific excellence in oral disease and gon Health & Science University, seeks course. Moravian College is located in developmental biology. We invite qualified students for its M.S. and the historic Lehigh Valley of Eastern applicants for the John W. Hein Research Ph.D. programs. The departmental Pennsylvania near Philadelphia and Fellowship. The fellowship provides focus on research and teaching New York City. Send a curriculum vita, generous salary compensation, benefits, addresses environmental systems graduate and undergraduate and infrastructure to develop a research through approaches on all relevant transcripts, statements of teaching program mentored by a Forsyth scales; leverages exciting advances in philosophy and research plans researcher. Support will be for 2 years biomolecular science and information including equipment and facility technology; and recognizes the close needs, and three letters of with the possibility of an additional year. connections between human and recommendation to Professor R. Applicants should have a Ph.D., MD, or ecosystem health. All M.S. and Ph.D. Daniel Libby, Chair, Department of DDS degree, and be US citizens, students are eligible for financial assis- Chemistry, Moravian College, 1200 permanent residents, or holders of J1 or tance. Candidates applying to the Main St., Bethlehem, PA 18018. H1 visas with the view to obtaining US Ph.D. program will automatically be Thorough consideration will be residency. Candidates who develop considered for fellowships that provide assured to applications completed by innovative and productive research an annual stipend, fully-paid tuition, January 12, 2004. Moravian College, programs have the potential to become and fully-paid health insurance. For an equal opportunity employer, Forsyth faculty members. Applicants more information, visit the depart- especially encourages applications should visit the Forsyth web site mental Web site at www.ebs.ogi.edu or from women and minority candidates. (http://www.forsyth.org) for information contact Therese Young at regarding research activities, and to [email protected] or 503-748-1247. POST-DOCTORAL RESEARCH FELLOW The OGI School of Science & Engi- (Job $4096) identify a potential mentor(s). A cover letter indicating research interest and neering is one of the four schools of A position is available at the Puget mentor, together with a CV that includes Oregon Health & Science University, Sound Blood Center in Seattle, WA to contact information for 3 referees should an equal opportunity, affirmative study megkaryocyte development action institution. be sent to Dr. Margaret Duncan, and thrombopoiesis. Project will Chairman, JWH Committee, The focus on signal transduction in BIOCHEMIST Forsyth Institute, 140 Fenway, Boston, hematopoietic cells and genetic MA 02115. Affirmative Action/Equal Moravian College studies of inherited platelet disorders. Opportunity Employer. Moravian College, a 260 year old, Candidates must have a Ph.D. or highly selective, liberal arts college M.D. degree, a background in with an ACS approved chemistry hematopoiesis, genetics, or signal program, and 1400 undergraduates, Place your Career transduction, and a valid Visa seeks applications for a tenure-track permitting work in the United States. assistant professorship in biochemistry Ads in ASBMB Today beginning September 2004. The Experience with tissue culture, Recruitment advertising is successful candidate will hold a Ph.D. molecular biology techniques, and available in ASBMB Today for $12 in chemistry or biochemistry and have protein analysis is desirable. Salary is per line, 10 line minimum. Copy is the ability to teach a variety of in accordance with NIH post-doctoral due by the first of the month prior chemistry courses. The position pay scale. Qualified applicants should to the issue month. For recruitment requires a commitment to teaching send their curriculum vitae and the advertising information call Veronica at FASEB AdNet, 800-433- and research in an undergraduate names of three references to: Human 2732 ext. 7791 or 301-634-7791, environment that emphasizes close Resources, Puget Sound Blood Center, student-faculty interaction. The email: [email protected] 921 Terry Avenue, Seattle, WA 98104- Display space is also available for primary teaching responsibility is the 1256, or email to creation of an upper-level those desiring greater visibility. [email protected]. biochemistry course, including the

DECEMBER 2003 ASBMBToday 23 Calendar of Scientific Meetings

DECEMBER 2003 MARCH 2004 American Society for Cell Biology 43rd Annual Meeting Association for Biomolecular Resource Facilities December 13–17 • San Francisco, California 2004 Annual Meeting Late Abstract Submission/Revision Deadline: October 14, 2003 February 28-March 2 • Portland, Oregon Ph: 301-347-9300; Fx: 301-347-9310 Abstract Deadline: November 21, 2003 Website: http://www.ascb.org/meetings/am2003/main03mtg.htm Early Registration Deadline: January 16, 2004 Ph: 301-634-7010; Fx: 301-634-7014; Email: [email protected] Selenium Biochemistry 2003: Celebrating 30 Years of Website: www.faseb.org/meetings/abrf2004 Selenoprotein Research December 17-19 • Bethesda, Marland APRIL 2004 Ph: 407-823-4262;Email: [email protected] Website: http://www.nhlbi.nih.gov/meetings/se2003.htm Experimental Biology 2004 April 17–21 • Washington, DC FEBRUARY 2004 Deadline for Submission of Abstracts: November 12, 2003 Website: http://www.faseb.org/meetings/eb2004/ Second International Conference on Ubiquitin, Ubiquitin-Like Proteins, and Cancer Xth International Symposium on Amyloid and February 5-7 • University of Texas M. D. Anderson Cancer Amyloidosis Center, Houston April 18-22 • Tours, France To allow for the optimal exchange of ideas, the conference will A transdisciplinary meeting that will be limited to 175 attendees, who will be selected based on address basic as well as clinical aspects of this field past contributions and/or newly developed interests in this Deadline for Receipt of Abstracts: December 15th, 2003 field. In addition to the invited speakers, all attendees are Abstracts must be submitted in English and only via the web encouraged to present posters and some will be invited to via http://www.colloquium.fr/isaa2004 where you will find all present them at the podium. Due to the limited number of the necessary information for submission. attendees, you are encouraged submit online applications prior COLLOQUIUM-ISAA2004, 12 rue de la Croix-Faubin to the November 15, 2003 deadline. 75557 PARIS cedex 11 (France); Ph: +33 (0)1 44 64 15 15 Contact: Amy Heaton; Ph: 713-745-6826 Fx: +33 (0)1 44 64 15 16; email: [email protected] email: [email protected]; website: http://www.sentrin.org

Biophysical Society 48th Annual Meeting JUNE 2004 February 14–18 • Baltimore, Maryland American Society for Biochemistry and Molecular Abstract Deadline: October 5, 2003 Biology Annual Meeting and 8th IUBMB Conference Early Registration Deadline: December 12, 2003 Ph: 301-634-7114; Fx: 301-634-7133 June 12–16 • Boston, Massachusetts Website: http://www.biophysics.org/annmtg/site-index.htm Contact: Kelly Gull; Ph: 301-634-7145; Fx: 301-634-7126 Email: [email protected]; Website: www.asbmb.org/meetings 50th Anniversary Gordon Conference on Isotopes in Biological and Chemical Sciences JULY 2004 February 15–20 • Ventura, California Chair: David N. Silverman, Vice Chair: Charles L. Perrin 4th ANNUAL CONFERENCE OF FOCIS (Federation of Email: [email protected] Clinical Immunology Societies) Website: http://www.grc.org/programs/2004/isotopes.htm July 18-23 • Montréal, Canada Deadlines The 1st Gordon Research Conference on The Biology of Abstract submission: January 23, 2004 14-3-3 Proteins Travel Award applications (CSI and ICI: November 15, 2003 Travel Award applications (FOCIS): January 23, 2004 February 22–27 • Ventura, California Early Registration: April 30, 2004; Website: Chairs: Haian Fu & David Klein, Vice-Chair: Alastair Aitken www.immuno2004.org Email: [email protected] Website: http://www.grc.org/programs/2004/14-3-3.htm

24 ASBMBToday DECEMBER 2003 Department Heads Take Note:

AUGUST 2004 12th International Conference on Second Messengers ASBMB Offers and Phospoproteins August 3–7 • Montreal, Canada Free Membership to Contact: [email protected] Website: http://www.secondmessengers2004.ca New Ph.D.s

SEPTEMBER 2004 ASBMB is now offering a free one-year Stem Cell Biology: Development and Plasticity Associate membership to all students who have, within the past year, earned a Ph.D. September 16-19 • Scheman Continuing Education Building Iowa State UniversityAmes, Iowa. degree in the molecular life sciences or Deadlines: Abstracts due July 16, 2004; registration deadline: related areas. August 16, 2004 ASBMB implemented this program as a Travel Grants: Students may apply for travel grants (applica- way to recognize the significant tions due July 16, 2004). Contact: Growth Factor and Signal Transduction Conferences accomplishment of earning the Ph.D., and to Symposium Office, 3208 Molecular Biology Building, Iowa provide new Ph.D.s with something tangible State University,Ames, Iowa 50011-3260 and of economic value. Membership in Ph: 515-294-7978; Fx: 515-294-2244; Email: [email protected] ASBMB brings with it a free subscription to Website: http://www.bb.iastate.edu/-gfstlhomepg.htmi the online versions of the Journal of Biological Chemistry and Molecular and Cellular NOVEMBER 2004 Proteomics, as well as subscriptions to The Scientist and the Society’s magazine, ASBMB 4th International Congress on Autoimmunity Today, discounts on other publications, and a November 3–7 • Budapest, Hungary host of other benefits. Deadline for Receipt of Abstracts: June 20, 2004 Contact: 4th International Congress on Autoimmunity Kenes The Society is asking department chairs International—Global Congress Organisers and Association to provide ASBMB with the names and Management Services,17 Rue du Cendrier, PO Box 1726, addresses of each new Ph.D. recipient from CH-1211 Geneva 1, SWITZERLAND their institutions. Upon receipt of this Ph: +41 22 908 0488; Fx: +41 22 732 2850 information, we will write the new Ph.D.s to Email: [email protected] congratulate them on their accomplishment Website: www.kenes.com/autoim2004 and offer the free one-year membership in ASBMB. Names and addresses of the new American Association of Pharmaceutical Scientists Ph.D.s should be sent to: AAPS Annual Meeting and Exposition November 7-11 • Baltimore, Maryland Kathie Cullins Ph: 703 243 2800; Fx: 703 243 9650 Membership and Subscriptions Manager Website: www.aapspharmaceutica.com/meetings/futuremeetings/ American Society for Biochemistry & Molecular Biology 9650 Rockville Pike DECEMBER 2004 Bethesda, MD 20814 Email: [email protected] American Society for Cell Biology 44th Annual Meeting This is an ongoing project; please advise us December 4-8 • Washington, DC whenever a student in your department earns the Ph: 301-347-9300; Fx: 301-347-9310 Ph.D., so that we can make this free membership Website: http://www.ascb.org/ offer to him or her. IUBMB/ASBMB 2004 “A Molecular Exploration of the Cell”

June 12 – 16 Boston, MA

American Society for Biochemistry and Molecular Biology Annual Meeting and 8th IUBMB Conference

l Biology ■ Mole ■ Chemica cular Recog atics nition ■ nform Ce Bioi llula and r Bi ics och om em te ist Pro Opening Lecture ry First Annual Herbert Tabor/Journal of Biological Chemistry Lectureship Robert J. Lefkowitz, HHMI, Duke University Medical Center

Organized by: John D. Scott, HHMI, Vollum Institute; Alexandra C. Newton, UCSD; Julio Celis, Danish Cancer Society, and the 2004 ASBMB Program Planning Committee

Cellular Organization and Dynamics Regulation of Gene Expression and Organizer: Harald A. Stenmark, Norwegian Rad. Hosp. Chromosome Transactions Organizer: Joan W. Conaway, Stowers Inst. for Med. Res. Genomics, Proteomics and Bioinformatics Organizers: Charlie Boone, Univ. of Toronto and Signaling Pathways in Disease Michael Snyder, Yale Univ. Organizers: Alexandra Newton, UCSD and John D. Scott, HHMI, Vollum Inst. Integration of Signaling Mechanisms Organizer: Kjetil Tasken, Univ. of Oslo, Norway The Future of Education and Professional Development in the Molecular Life Sciences Molecular and Cellular Biology of Lipids Organizer: J. Ellis Bell, Univ. of Richmond Organizer: Dennis Vance, Univ. of Alberta

Molecular Recognition and Catalysis For further information: Organizer: Jack E. Dixon, UCSD ASBMB 9650 Rockville Pike Protein Modifications and Turnover Bethesda, MD 20814 Organizer: William J. Lennarz, SUNY at Stony Brook Tel: 301-634-7145 Fax: 301-634-7126 Protein Structure, Catalysis and Dynamics Email: [email protected] Organizer: Susan Taylor, UCSD http://www.asbmb.org/meetings www.asbmb.org/meetings Abstract Deadline: February 4, 2004