NOVEMBER 2004 www.asbmb.org

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AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY

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ASBMB Comments on NIH Public Access Notice Page 5 AxelAxel andand BuckBuck AAwardedwarded 20042004 NobelNobel PrizePrize

SAN DIEGO 2005: Call for Late-Breaking Abstracts see page 5

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AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY NOVEMBER 2004, Volume 3, Issue 8 features 5 ASBMB Comments on NIH Public Access Notice

6 Senate Hearing on Stem Cell Controversy

7 Congress Adjourns; Lame Duck Session Coming

8 Lasker Award Goes to Elwood Jensen 20

10 Pharmacological Chaperones

14 Coordinate Regulation of Transcription

ON THE COVER: 16 Catalysis: Structure, Function, and Evolution

12 Axel, Buck 19 William Dowhan to Get Avanti Award Awarded 2004 Nobel 20 Jack Dixon to Receive ASBMB-Merck Award

22 Jan-Åke Gustafsson Wins Bristol-Myers Squibb

23 JBC Launches Papers of the Week

26 Steven McKnight Wins NIH Award

AWARDS OF EXCELLENCE: MOST IMPROVED MAGAZINE 10 COLUMNS & EDITORIALS DESIGN & LAYOUT departments 2 Letters 6 News From the Hill 26 NIH News 28 Biotech Business 31 Career Opportunities

BRONZE AWARD WINNER 2003 32 Calendar LETTERS

ASBMB Council

Officers Judith S. Bond President Bettie Sue Masters Past-President Peggy J. Farnham Secretary Kenneth E. Neet Treasurer Council Members William R. Brinkley Councilor State Dept. Official Sees Joan W. Conaway Councilor Robert A. Copeland Councilor Lila M. Gierasch Councilor (The following letter, dated September 7, to Frederick P. Guengerich Councilor ASBMB President Judith Bond, is in response to William J. Lennarz Councilor Peter J. Parker Councilor the Society's support of an American Association William S. Sly Councilor for the Advancement of Science (AAAS) paper, William L. Smith Councilor "Statement and Recommendations on Visa Ex-Officio Members George M. Carman Problems Harming America's Scientific, Economic, Chair, Meetings Committee Cecile Rochette-Egly and Security Interests." An article announcing Dennis R. Voelker Co-chairs, 2005 Program Committee ASBMB's support for the AAAS statement appeared J. Ellis Bell on page 6 in the June issue of ASBMB Today.) Chair, Education and Professional Development Committee Juliette Bell Dear Ms. Bond: applying to U.S. colleges and universi- Chair, Minority Affairs Committee William R. Brinkley In May 2004 you joined with several ties. I am keenly aware that scientific Chair, Public Affairs Advisory Committee of your colleagues in the American sci- and academic exchanges underpin Christopher K. Mathews Chair, Publications Committee entific, academic and engineering U.S. national security as surely as bor- Herbert Tabor communities to express your concerns der protection against overt threats to Editor, JBC about post-September 11 border secu- the U.S., and we have worked relent- Ralph A. Bradshaw Editor, MCP rity requirements and the perceived lessly to ensure that the necessary Edward A. Dennis impact they were having on these security improvements to the visa Editor, JLR communities. We in the Bureau of process do not come at the cost of ASBMB Today Consular Affairs have been working legitimate travelers. We have much is a monthly publication of The American Society for with our colleagues in the Department success to report. Biochemistry and Molecular Biology of Homeland Security and other fed- First, we have coordinated closely Editorial Advisory Board eral agencies to improve the processing with the interagency community to Irwin Fridovich of visa applications for students and ensure that special clearance procedures Richard W. Hanson researchers. that impact the very small percentage of Bettie Sue Masters I will be the first to admit that new student visa applications that require Evan J. Sadler Robert D. Wells security procedures affecting students them are processed as quickly as possi- Comments and scientists initially resulted in ble. Our efforts have had real results. As Please direct any comments or questions lengthy delays. Perhaps more impor- of September 2, 98 percent of all Visa concerning ASBMB Today to: tantly, a perception developed that it Mantis cases are being cleared in less

John D. Thompson has become harder to study or con- than 30 days. More than 2,000 ongoing Editor, ASBMB Today duct research in the United States. cases were just cleared. Striving to 9650 Rockville Pike Misunderstandings about U.S. visa enhance the transparency and pre- Bethesda, MD 20814-3996 Phone: 301-634-7145; Fax: 301-634-7126 policies, coupled with inaccurate anec- dictability of the visa application E-mail: [email protected] dotal information and factors unre- process, we have recently begun posting For information on advertising lated to visa processing, fueled visa appointment wait times on the contact FASEB AdNet at 800-433-2732 negative perceptions about study or internet at www.travel.state.gov. All of ext. 7157 or 301-634-7157, or email [email protected]. research in the U.S., which may have our embassies and consulates have been actually discouraged students from instructed to provide expedited visa

2 ASBMBToday NOVEMBER 2004

LETTERS

Improvement in Visa Processing appointments to student visa applicants academics and scientists are returning ing misperceptions regarding the visa to ensure that eligible applicants can to the U.S. in increasing numbers over application process and reinforcing our start their programs on time. Addition- last year. Overall, the number of non- message that the United States contin- ally, we continue to work closely with immigrant visa applications we receive ues to be a welcoming nation. I look the Department of Homeland Security is increasing, and we expect student forward to working with you to ensure on issues related to the implementation visas to follow suit for the next aca- that the United States remains the pre- of SEVIS and the Department of Home- demic year. eminent destination for students, aca- land Security on issues related to the It is time to change the tenor of the demics and scientists. implementation of SEVIS and the SEVIS dialogue on this issue and support the fee so that these programs can be as resurgence of students and scientists Sincerely, streamlined and as effective as possible. applying for—and receiving—their Maura Harty Recent media reporting and our own visas in a timely manner. I ask you to Assistant Secretary of State visa statistics indicate that students, join with me in countering the linger- for Consular Affairs Get PowerPoint Presentations From JBC, JLR, MCP, and BAMBED

In order to better serve our readers, we, with our partners at HighWire Press, have added a new online feature to The Journal of Biological Chemistry, Journal of Lipid Research, Molecular and Cellular Proteomics, and Biochemistry and Molecular Biology Education websites that allows a reader to download of a figure directly to Power Point. Many readers use figures from JBC papers for teaching and this feature facilitates that process. The figure is automatically loaded into PowerPoint along with the citation information.

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enter AT114 to win a LAB PAL l L w or call 1-800-897-5876. A a y P Specific laboratory s B symbols be LA certain with ASBMB Comments on NIH Public Access Notice n a September 22, 2004, letter public online without delay.” Manu- such as HighWire Press, which “offer to NIH Director Elias Zer- scripts accepted for publication in JBC advanced searching, enhanced func- I houni, ASBMB President and other ASBMB journals, for exam- tionality and many other reader serv- Judith Bond signaled ASBMB’s support ple, appear in the Papers In Press (PIP) ices that are presently unavailable at for “the concept that scientific publica- section of the JBC website within a day PubMed Central and would require tions be made freely accessible to the or two of acceptance. Thus, the ASBMB additional funding to provide.” Finally, public in a timely manner.” Thus, letter notes, “the NIH proposal will not she noted that only about 40 percent ASBMB supports the recently proposed enhance public access to ASBMB arti- of the Journal of Biological Chemistry’s NIH policy of making NIH-funded cles beyond that already in place.” content was from NIH-supported research papers accessible to the public ASBMB also notes its opposition to investigators, so PubMed Central six months after publication. “the proposal that the final redacted would house only a fraction of the bio- Under the NIH proposal (announced publisher’s version of papers be chemistry literature. in September in the NIH Guide to deposited in PubMed Central.” While The ASBMB letter is on-line at the Grants and Contracts and the Federal this was not strictly speaking a pro- Society homepage (www.asbmb.org). Register), NIH requests “that its grantees posal in the NIH notice—the notice Click on “public affairs”, go to “policy and supported Principal Investigators merely indicated that publishers could statements,” and scroll down to “elec- provide the NIH with electronic copies provide the final published version of tronic publishing.” The statement is of all final version manuscripts upon the paper if they chose—Dr. Bond pro- listed there. acceptance for publication if the posed instead that “the NIH link to the The NIH notice on “Enhanced Public research was supported in whole or in publisher’s versions of the articles.” Access to NIH Research Information” part by NIH funding.” A “final manu- Linking was proposed for several rea- appeared in the Federal Register on Sep- script” is defined as “the author’s ver- sons: to “avoid the existence of two tember 17 (69 FR 56074). Comments sion resulting after all modifications due official versions of the published docu- from the public are being accepted at to the peer review process.” ments, reducing files, and avoid gov- “[email protected]” through The NIH notice also states, “Six ernment control of the scientific November 16, 2004. ASBMB strongly months after an NIH supported literature.” Dr. Bond also noted the urges all interested persons to comment research study’s publication—or sooner vast superiority of existing archives on this important NIH notice. if the publisher agrees—the manu- script will be made available freely to the public through PubMed Central ASBMB ANNUAL MEETING 2005 (PMC). If the publisher requests, the author’s final version of the publica- Call for Late-Breaking Abstracts tion will be replaced in the PMC archive by the final publisher’s copy Deadline for Submission: Wednesday, February 9, 2005 with an appropriate link to the pub- lisher’s electronic database.” Abstracts must be submitted electronically with payment of $90 and In ASBMB’s letter to Dr. Zerhouni, received on or before Wednesday, February 9, 2005. Dr. Bond notes that while ASBMB sup- ports the NIH’s intent to provide pub- lic access to NIH-funded research Late-breaking abstracts will be accepted for special poster sessions manuscripts six months after publica- to be scheduled on Tuesday, April 5, 2005. tion, the NIH’s proposal actually has little if any impact on ASBMB publica- Save Money! Register online by February 4 and make your housing tions. “For ASBMB journals,” she reservations by February 21, 2005. notes, “all manuscripts accepted for publication are freely available to the

NOVEMBER 2004 ASBMBToday 5

NEWS FROM THE HILL

by Peter Farnham, CAE, ASBMB Public Affairs Officer

Senate Hearing on Stem Cell Controversy n September 29, Senator Ethics Addressed in the religious, historical and philosophi- Sam Brownback (R-KS) held First Panel cal framework and precedents for that O a hearing in the Senate Sub- The first panel explored some of the perspective. She noted that nearly all committee on Science, Technology ethical issues involved in the debate Jews, most Muslims, and many Bud- and Space called “Embryonic Stem over whether to use hESC or not. It dhists and Protestants believe it Cell Research: Exploring the Contro- mainly focused on exploring the ques- “morally imperative” to use human versy.” Although nothing new and tion of when life begins. Dr. Laurie blastocysts to create stem cell lines if it revolutionary was revealed at the Zoloth, Director of Bioethics at North- can lead to saving lives or healing. hearing, it was unusual for a Brown- western University Center for Genetic Doerflinger testified that an embryo back-led hearing in that he invited Medicine, presented the pro-hESC per- already is recognized as a member of human embryonic stem cell (hESC) spective, while Richard Doerflinger, the human family in numerous areas of proponents to testify, as well as Deputy Director of the Secretariat for federal law. He said, “At every stage of opponents. Members attending in Pro-Life Activities at the U.S. Confer- development, the unborn child in the addition to Brownback included Ron ence of Catholic Bishops, presented womb is protected by federal homicide Wyden (D-OR), John Ensign (R-NV) opposition to hESC research. laws as a separate victim when there is a and Byron Dorgan (D-ND). It Zoloth maintained the view that an violent attack upon his or her mother.” appeared to be a fairly partisan hear- embryo, particularly one created by in He added that the same embryo is rec- ing, with Democrats generally in vitro fertilization techniques and due to ognized in federal health regulations as favor of hESC research, and Republi- be discarded, was not the moral equiva- a patient eligible for prenatal care. He cans opposed. lent of a human being. She explained also repeated his belief that life begins at the moment of fertilization, and any destruction of an embryo after that was equivalent to the taking of a human New Terms for Stem Cell Research life. He also indicated his opposition to The International Society for Stem stem cell lines by the transfer of in vitro fertilization. Cell Research (ISSCR) has recently body cell (somatic) nuclei into enu- Senator Brownback insisted in his approved several new terms for stem cleated eggs of the same species, and opening remarks that “when we say cell research. First, the ISSCR recom- the negative connotation of the life begins at the earliest stage, biology mends use of the acronym “hESC” in commercial term ‘therapeutic is being discussed, not theology.” He place of any other acronyms that have cloning,’ make a change in terminol- continued, “To assert that an embryo been used to reference “human ogy necessary. The aim of this termi- is not a human life is inaccurate . . . the embryonic stem cells” derived from nology change is to provide accurate, issue of where human life begins is at pre-implantation blastocysts produced standardized terminology that will the heart of what we’re discussing” by sperm-egg fertilization. ISSCR also facilitate frank scientific, ethical and during the hearing. recommends use of the term “nuclear public debate on stem cells and their transfer” to replace the term “thera- potential for medicine.” Panel focuses on peutic cloning.” Cells created by ISSCR encourages its members and potential for cures, nuclear transfer should be described as the scientific press to use these these therapies “NT stem cells,” or “NTSC.” terminologies in publications, pre- Dr. George Daley, Associate Profes- According to an ISSCR statement, sentations and communications. sor of Pediatrics, Harvard School of “the inaccurate use in various public The complete statement is avail- Medicine, testified for hESC, on behalf and scientific venues of various able on the ISSCR website, at of the American Society for Cell Biol- terms dealing with the production of www.isscr.org ogy. He focused on the current state Continued on page 9

6 ASBMBToday NOVEMBER 2004

NEWS FROM THE HILL

Congress Adjourns Without Completing Work; Lame Duck Session Planned ongress abandoned all efforts NIH—$28.6 billion, about $700 mil- ent agencies, on September 21. In to complete work on remain- lion, or a 2.7 % increase, above 2004 some good news for this chronically C ing funding bills in late Sep- levels. The Senate version passed the underfunded agency, the Senate bill tember, instead shifting efforts to Appropriations Committee on Septem- raises the NSF budget by $167 mil- passing a continuing resolution (CR) ber 15, and contains some additional lion, matching the President’s request. before adjournment, scheduled for funds for NIH. The Senate bill funds The Senate bill would fund NSF at mid-October. The CR would fund the NIH at $28.9 billion, about $1.1 bil- $5.74 billion in fiscal year 2005. government at Fiscal Year 2004 levels lion, a 4 % increase, over the fiscal year Although this amounts to only a 3 % through the upcoming election; it 2004 bill’s total. increase, it stands in sharp contrast to would be in effect until November 20. Rep. Ralph Regula (R-OH), chairman the $111 million cut proposed in the Congress plans to reconvene sometime of the House Appropriations subcom- House appropriations bill, which in November to finish up the 12 passed the House Appropriations remaining appropriations bills. So far, Committee on July 22. the only bill signed into law is the NSF advocates, while pleased with defense appropriations bill. the Senate action relative to what The two appropriations bills ASBMB would have been in store if the House is most concerned about—Labor/HHS version had become law, are under no and HUD/VA—are currently languish- illusions about what the future holds. ing in legislative limbo with no The House and Senate versions must progress expected before Thanksgiving. be reconciled in conference, which Further, there is a good chance that means a “split the difference” figure they will be lumped into an omnibus resulting in an increase somewhere in appropriations bill, in which some or the $50 million range is a real possibil- all of the remaining bills are combined ity. The Senate proposal is also far into a gigantic funding vehicle. It short of the total for FY 2005 recom- would (in theory) be easier for Congress mended in the NSF authorization to pass one appropriations bill rather bill—$7.38 billion—which President than twelve; however, such a course is Bush signed into law with great fanfare fraught with danger, as a small group of in December 2002. This bill would recalcitrant lawmakers could hold up double the NSF budget over five years. the whole bill over one or two small, The Senate bill would The committee report accompany- relatively unimportant provisions. ing the Senate appropriations bill fund NSF at $5.74 acknowledges the deviation from the House, Senate Differ billion. Although this NSF doubling plan: “The Committee on NIH Funding amounts to only a 3 % continues to be supportive of…the Funding for the National Institutes pursuit of a doubling path for NSF of Health (NIH) is found in the increase, it stands in funding. However, due to funding Labor/HHS appropriations bill, and sharp contrast to the constraints, the Committee is not able this year’s version passed the House on to provide such funding at this time, $111 million cut September 9. The 2005 spending bill but will continue to pursue these supported the President’s request for proposed in the House. efforts in the future.”

NOVEMBER 2004 ASBMBToday 7

Lasker Award Goes to Elwood Jensen he 2004 Lasker Award for proved that hormones do not In 1967, he and Basic Medical Research has undergo chemical change. Instead, Dr. Jack Gorski T been presented to Elwood they bind to a receptor protein of the University Jensen, Charles B. Huggins Distin- within the cell. This hormone-recep- of Wisconsin guished Service Professor Emeritus in tor complex then travels to the cell showed that these the Ben May Institute for Cancer nucleus, where it regulates gene putative receptors Research at the University of Chicago. expression. At the time, this idea was were macromole- He shares the award with Dr. Pierre heresy. When he first presented pre- cules that could be Chambon, Institute of Genetics and liminary data at a 1958 meeting in extracted from Dr. Elwood Jensen Molecular and Cellular Biology in Vienna, only five people attended, these tissues. With this method, Dr. Strasbourg, France, and Dr. Ronald M. three of whom were the other speak- Jensen showed that when estrogen Evans, Salk Institute for Biological ers. In the next 20 years though, he bound to this receptor, the compound Studies and the Howard Hughes Med- then migrated to the nucleus where it ical Institute. Dr. Jensen is being bound avidly and activated specific They were selected for their discov- honored for his genes, stimulating new RNA synthesis. ery of the “superfamily of nuclear hor- He subsequently devised a reliable test mone receptors and the elucidation of pioneering research for the presence of estrogen receptors in a unifying mechanism that regulates on how steroid breast cancer cells,and showed that embryonic development and diverse women with receptor-rich breast can- hormones, such as metabolic pathways.” The implications cers often have remissions following of this research for understanding estrogen, exert their removal of the sources of estrogen, but human disease and accelerating drug influence. His cancers that contain few or no estrogen discovery “have been profound and receptors do not respond to estrogen- hold much promise for the future,” discoveries led to the blocking therapy. notes the announcement from the development of drugs By 1977, Dr. Jensen and Dr. Geoffrey Lasker Foundation. This awards were that can enhance or Greene, also in the University of presented at a luncheon ceremony, Chicago’s Ben May Institute, had October 1, in New York City. inhibit the process. developed monoclonal antibodies Dr. Jensen is being honored for his directed against estrogen receptors, pioneering research on how steroid convinced his colleagues by publish- which enabled them to quickly and hormones, such as estrogen, exert their ing a series of major and highly origi- accurately detect and count estrogen influence. His discoveries explained nal discoveries in four related areas of receptors in breast and other tumors. how these hormones work, which led hormone research. This test became a standard part of to the development of drugs that can Dr. Jensen discovered the estrogen care for breast cancer patients and as enhance or inhibit the process. receptor, the first receptor found for the Lasker Foundation noted, “trans- In the 1950s, biochemists thought a any hormone. In 1958, using a formed the treatment of breast cancer hormone entered a cell, where a series radioactive marker, he showed that patients and saves or prolongs more of oxidation and reduction reactions only the tissues that respond to estro- than a 100,000 lives annually.” with estrogen provided needed energy gen, such as those of the female repro- ”Jensen’s revolutionary discovery for the growth stimulation and other ductive tract, were able to concentrate of estrogen receptors is beyond doubt specific actions shown by estrogens. injected estrogen from the blood. This one of the major achievements in From the late 1950s to the 1970s specific uptake suggested that these biochemical endocrinology of our Dr. Jensen entirely overturned that cells must contain binding proteins, time,” recalled Gene DeSombre, Pro- notion. Working with estrogen, he which he called “estrogen receptors.” fessor Emeritus at the University of

8 ASBMBToday NOVEMBER 2004

Chicago, who worked with Dr. Jensen systems that control the body’s in the Ben May Institute as a post- response to essential nutrients (such Stem Cell Controversy doctoral fellow and then as a col- as Vitamin A), fat-soluble signaling continued … league. “His work is hallmarked by molecules (such as fatty acids and bile great technical ingenuity and concep- acids), and drugs (such as the glita- Continued from page 6 tual novelty. His promulgation of zones used to treat Type 2 diabetes of the science and the need for more simple yet profound ideas concerning and retinoic acid for certain forms of stem cell lines, and disputed the claim the role of receptors in estrogen acute leukemia). that adult stem cells had equivalent action have been of the greatest These three individuals “created the potential to hESC. importance for research on the basic field of nuclear hormone receptor Dr. Marc Hedrick of Macropore Bio- and clinical physiology not only of research, which now occupies a large surgery testified on his company’s estrogens but also of all other cate- area of biological and medical investi- progress with adult stem cells derived gories of steroid hormones.” gation,” said Dr. Joseph L. Goldstein, from adipose tissue. In a similar vein, By the early 1970s, Dr. Jensen was Chair of the international jury of Dr. David Prentice of the Family searching for chemical, rather than researchers that selects recipients of the Research Council argued for adult stem surgical, ways to shield estrogen- Lasker Awards, and a recipent of both cell research and against hESC research. dependent tumors from circulating the Lasker Award for Basic Medical The general tone set by Chairman hormones. He and Dr. Craig Jordan Research and the Nobel Prize in Medi- Brownback was the great promise of (then at Massachusetts’ Worcester cine in 1985. adult stem cells (in his view), and how Foundation for Experimental Biology) They revealed the “unexpected and they are already producing therapies. found that women with cancers con- unifying mechanism by which many This view was supported by Prentice taining large amounts of estrogen signaling molecules regulate a plethora and Hedrick. Clinical studies were receptor are likely to benefit from of key physiological pathways that cited in which patients suffering from tamoxifen, which blocks some of the operate from embryonic development heart disease were treated with bone effects of estrogen. Patients with few through adulthood. They discovered a marrow stem cells and showed or no receptors could immediately family of proteins that allows chemi- improvement. move on to chemotherapy rather than cals as diverse as steroid hormones, Dr. Daley maintained that there was waiting months to find out that the Vitamin A, and thyroid hormone to no evidence in those studies that adult tumors were growing despite tamox- perform in the body.” stem cells were showing plasticity (i.e. ifen treatment. Other researchers sub- The Lasker Awards are the nation’s becoming new heart muscle), but sequently found that the receptors for most distinguished honor for out- rather seemed to be producing growth the other major steroid hormones, standing contributions to basic and factors or other proteins that were such as testosterone, progesterone, clinical medical research. Often called restoring heart function. and cortisone, worked essentially the “America’s Nobels,” the Lasker Award The question posed most often was, same way. has been awarded to 68 scientists who if hESC were so promising, why In 1986, Dr. Pierre Chambon and subsequently went on to receive the weren’t there any clinical trials involv- Dr. Ronald Evans separately but Nobel Prize, including 15 in the last ing this, the way there were for adult simultaneously discovered that the 10 years. Lasker Award recipients stem cells? Dr. Daley responded that steroid hormone receptors were receive an honorarium, a citation adult stem cells had been studied for a merely the tip of the iceberg of a large highlighting their achievements, and half century or more, while hESC had family of structurally related nuclear an inscribed statuette of the Winged been studied only since 1998. receptors with 48 members. They Victory of Samothrace representing unearthed a number of these recep- humanity’s victory over disability, dis- Carrie Golash of FASEB’s Office of Public tors, which revealed new regulatory ease, and death. Affairs contributed to this article.

NOVEMBER 2004 ASBMBToday 9

Pharmacological Chaperones Show By Nicole Kresge, Science Writer

iseases, such as hypogo- allowing them to pass the quality con- The therapeutic potential of pharma- nadotropic hypogonadism trol apparatus of the cell and undergo coperones has been demonstrated by D (HH), cystic fibrosis, and retini- proper routing. The molecules are then Dr. Conn and his colleagues. The tis pigmentosa, are caused by misfolding able to function indistinguishably researchers showed that all but three of mutations resulting in proteins being from wild type molecules. The efficacy 18 naturally occurring mutations caus- misrouted. Previous efforts at finding of this approach is changing the scien- ing HH in humans, as well as other treatments for these diseases have tists think about the effect of muta- “designer” mutants with truncations focused on gene therapy. Now, an alter- tions and suggests that mutants are and deletions, can be rescued in vitro by native therapy is emerging with the dis- frequently misrouted, but otherwise the pharmacoperone IN3, despite the covery that certain small molecules can potentially functional proteins. fact that the mutations are widely scat- restore correct routing—and therefore “This has profound implications for tered throughout the receptor protein. function—to mutant receptor proteins. therapeutic approaches since correction HH is characterized by delayed sex- Scientists have found that small of protein routing has proven to be ual development and abnormally low pharmacological chaperones (or “phar- much less challenging than replace- levels of sex steroids and gonadotropic macoperones”) that stabilize the ment of a defective gene with a perfect hormones. The disorder is caused mutant proteins enable them to be one using gene therapy,” says P. Michael by misfolding mutations in the routed correctly. These pharmacoper- Conn,* Associate Director of the Ore- gonadotropin-releasing (GnRH) recep- ones reshape misfolded proteins, gon National Primate Research Center. tor. Although the misfolded proteins

10 ASBMBToday NOVEMBER 2004

Promise for Disease Treatment are not irreversibly damaged by the mutation, they are retained in the endoplasmic reticulum. This retention prevents the receptors from reaching the plasma membrane where they nor- mally bind GnRH and activate a signaling pathway leading to gonadotropin transcription. “As part of normal routing to the plasma membrane from the endoplas- mic reticulum, many proteins, notably G- protein coupled receptors, such as the GnRH receptor, appear to oligomerize. It turns out that mutants can oligomerize with wild type mole- cules, causing wild type molecules to misroute, as well; this is the basis of a dominant negative effect. In vivo this means that the mutant can have a dis- proportionately large effect—one that may be rescued by pharmacoperones,” notes Dr. Conn. This discovery was . Michael Conn. recently published by Dr. Conn and his colleagues in the July 2004 issue of Molecular Endocrinology. IN3 was originally designed by Merck as an orally active, nonpeptide receptor Image by Joel Ito and P antagonist for the GnRH receptor. “IN3 Mutants of the gonadotropin releasing hormone (GnRH) receptor (shown on envelope) are frequently and other pharmacoperones are small mis-routed, but otherwise functional, proteins that can be rescued by pharmacological chaperones— hydrophobic molecules that enter cells small molecules that cause them to fold correctly, then route to the correct cellular compartment. The observation that many human and animal diseases are caused by misfolded proteins is and act as molecular scaffolding—caus- drawing attention to the efficacy of this approach as a therapeutic venue. ing otherwise misfolded protein mutants to fold correctly and route cor- showing that mutants which rescue Small molecule protein ligands may rectly,” explains Dr. Conn. “Once the well with one chemical class, also res- also someday be used to cause proteins correctly folded mutant arrives at the cue with another. to undergo misfolding and removal. membrane, it is stabilized by The success seen in these experiments Dr. Conn explains, “Imagine that a hydrophobic interactions with the suggests that this technique could kinase that causes cancer or a receptor membrane and the drug can be potentially be used to treat HH and required for fertility could, instead of removed, leaving a fully competent other diseases resulting from misfolded, being routed correctly, be ‘ship- receptor with characteristics of the wild yet otherwise competent receptor pro- wrecked’ by a molecule that would type receptor.” In addition to IN3, an teins. In addition, pharmacoperones cause it to become misfolded and tar- indole structure, Dr. Conn’s lab has suc- could be used to prevent the accumula- geted for destruction. The means of cessfully used other chemical classes of tion and aggregation of proteins in neu- removing such proteins will likely pharmacoperones—quinolones and rodegenerative diseases such as present further opportunities for thera- erythromycin macrolides from TAP Alzheimer’s disease, Parkinson’s disease, peutic intervention.” and Abbott Laboratories, respectively— and prion diseases. *ASBMB Member

NOVEMBER 2004 ASBMBToday 11

Axel, Buck Awarded 2004 Nobel he Nobel Assembly at the cilia that protrude into a thin each was expressed only at a Karolinska Institute announced bath of mucus at the cell very low level.” T last month that the 2004 surface. Somewhere on Finally, Dr. Buck Nobel Prize in Physiology or Medicine these cilia, scientists came up with what was awarded to Richard Axel, an HHMI were convinced, Dr. Axel calls “an Investigator at Columbia University Col- there must be extremely clever lege of Physicians and Surgeons, and receptor proteins twist.” She made Linda Buck, an HHMI Investigator at the that recognize and three assumptions Fred Hutchinson Cancer Research Cen- bind odorant mole- that drastically nar- ter. The scientists were honored for dis- cules, thereby stimu- rowed the field, coveries that clarify how the olfactory lating the cell to send allowing her to zero system works. signals to the brain. in on a group of genes Dr. Axel and Dr. Buck discovered a The receptor proteins that appear to code for the large gene family, comprised of some would be the key to answering odorant receptor proteins. 1,000 different genes (three per cent of two basic questions about olfaction, Her first assumption—based on bits human genes) that give rise to an explained Dr. Axel. First, how does the of evidence from various labs—was equivalent number of olfactory recep- system respond to the thousands of that the odorant receptors look a lot tor types. These receptors are located molecules of different shapes and sizes like rhodopsin, the receptor protein on the olfactory receptor cells, which that we call odorants, “does it use a in rod cells of the eye. Rhodopsin and occupy a small area in the upper part restricted number of promiscuous recep- at least 40 other receptor proteins of the nasal epithelium and detect the tors, or a large number of relatively spe- criss-cross the cell surface seven times, inhaled odorant molecules. cific receptors?” And second, how does which gives them a characteristic, In 1991, Dr. Axel and Dr. Buck, then the brain make use of these responses to snake-like shape. They also function a postdoctoral fellow in the Axel lab, discriminate between odors? in similar ways, by interacting with G discovered a family of genes that The string of discoveries that totally proteins to transmit signals to the encode the odorant receptors of the changed the cell’s interior. Since many receptors of olfactory epithelium, a patch of cells study of olfaction this type share certain DNA on the wall of the nasal cavity. The resulted from a Dr. Richard Axel (below) and Dr. Linda Buck (left) olfactory epithelium contains some 5 new emphasis on million olfactory neurons that send genetics. Instead messages directly to the olfactory bulb of hunting for of the brain. When an odor excites a the receptor pro- neuron, the signal travels along the teins directly, the nerve cell’s axon and is transferred to two looked for the neurons in the olfactory bulb. This genes that con- structure, located in the very front of tained instructions for the brain, is the clearinghouse for the proteins found only in sense of smell. From the olfactory the olfactory epithelium. bulb, odor signals are relayed to both Their efforts produced the brain’s higher cortex, which han- nothing at first. “Now dles conscious thought processes, and we know why our initial to the limbic system, which generates schemes failed,” said Dr. emotional feelings. Axel. “It’s because there Each olfactory neuron in the epithe- are a large number of lium is topped by at least 10 hair-like odorant receptors, and

12 ASBMBToday NOVEMBER 2004

Prize in Physiology or Medicine sequences, she designed probes that The discovery made it possible to tip of the iceberg. It now appears that would recognize these sequences in a study the sense of smell with the tech- there are between 500 and 1,000 sepa- pool of rat DNA. niques of modern molecular and cell rate receptor proteins on rat and Next, she assumed that the odorant biology and to explore how the brain mouse—and probably human—olfac- receptors are members of a large family discriminates among odors. tory neurons. of related proteins. So she looked for It also allowed researchers to “pull Dr. Buck and Dr. Axel, an ASBMB groups of genes that had certain similari- out” the genes for similar receptor member, also were co-recipients in ties. Third, the genes had to be expressed only in a rat’s olfactory epithelium. “Had we employed only one of these criteria, we would have had to sort through thousands more genes,” said Dr. Axel. “This saved several years of drudgery.” Dr. Buck recalls that “I had tried so many things and had been working so hard for years, with nothing to show for it. So when I finally found the genes in 1991, I couldn’t believe it! None of them had ever been seen before. They were all different but all related to each other. That was very satisfying.”

“I had tried so many things and had been working so hard for years, with nothing to show for it. So when I finally found the genes in 1991, I couldn’t Odorant receptors and the organization of the olfactory system. believe it! None of proteins in other species by search- 2003 of the third annual Perl-Univer- them had ever been ing through libraries of DNA from sity of North Carolina Neuroscience seen before. They were these species. Odorant receptors of Prize. Dr. Buck is a member of the all different but all humans, mice, catfish, dogs, and Basic Sciences Division at the Fred salamanders have been identified in Hutchinson Cancer Research Center related to each other. this way. in Seattle and Affiliate Professor at the That was very The team’s most surprising finding University of Washington. Dr. Axel is was that there are so many olfactory University Professor of Biochemistry satisfying.” receptors. The 100 different genes the and Molecular Biophysics at Columbia —Linda Buck researchers identified first were just the University.

NOVEMBER 2004 ASBMBToday 13

Coordinate Regulation of Transcription Organizer : Cécile Rochette-Egly, Director of Research, IGBMC, Strasbourg, France

he correct regulation of gene co-regulators on gene regulatory Despite having a expression is a vitally important regions, concomitant with an alter- set of consensus T process. Controlling which ation in local chromatin structure. In subunits, the com- genes are turned on and when is this session, Franck Gannon (EMBL- position of the essential for normal growth and devel- Heidelberg Foundation for Research Mediator complex opment. Thus, cells have evolved elab- and Technology) will provide a com- may differ orate mechanisms to ensure that prehensive picture of cyclical networks depending on the genes are transcribed only when of association of the estrogen receptor target gene. Here, appropriate signals make their way to and transcriptional coregulators with a Joan Conaway Dr. Cécile Rochette-Egly the nucleus. An elaborate and care- target gene promoter, as determined by (Stowers Institute) will describe studies fully orchestrated series of interactions chromatin immunoprecipitation on the structure and function of the and dissociations between transcrip- assays. Iannis Talianidis (Institute of mammalian Mediator complex. tional regulators ensures formation of Molecular Biology and Biotechnology, Finally, Patrick Cramer (University of appropriate chromatin structure and FORTH) will describe the dynamic Munich) will present new structural correct recruitment of the transcrip- ordered recruitment of transcription studies of RNA polymerase II com- tional machinery at the promoter. In factors and chromatin remodelling plexes. Crystallographic models of the addition, the dynamics of such inter- complexes at the promoters of differ- complete Polymerase II, together with actions are fine tuned by a wide vari- entiation-induced genes. Then, how new biochemical and electron micro- ety of post-translational modifications the ARC mediator complex which is a scopic data, will give insights into such as phosphorylation, acetylation, large multiprotein transcriptional co- mechanisms of transcription initiation methylation and ubiquitination so activator, serves to transduce transcrip- and elongation. that the correct proteins are present tion activating signals from different with the right activity, at the right classes of activators to the RNA poly- Transcription activators: place, and at the right time. merase II transcriptional machinery integrators of diverse Equally important as transcription ini- will be discussed by Anders M. Naar signaling pathways tiation is mRNA elongation and matura- (Harvard Medical School). This symposium will focus on how tion. Indeed, it has become evident that integration of signals from a number mRNA processing occurs cotranscrip- Identification of new of pathways converge on transcrip- tionally and also involves coordinated complexes that regulate tion activators. Barbara Graves (Uni- series of post-translational modifications transcription versity of Utah, Huntsman Cancer that control the association and dissocia- Transcriptional activators recruit Institute), will discuss how phospho- tion of protein complexes. coregulators that contribute to tran- rylation by MAPKs induces conforma- scriptional activation by helping to tional changes in members of the Ets Dynamic and coordinated remodel chromatin structure and family of transcription factors and recruitment of recruit RNA Polymerase II and its asso- thereby controls their activities. Simi- activators and ciated basal transcriptional machinery. larly, Andrew Sharrocks (University of coregulators to gene Though a number of these co-regula- Manchester) will describe how MAPK- promoters tors have been characterized, new mediated phosphorylation of Elk1 A concept that has developed over adaptors are constantly being identi- regulates its ability to recruit coactiva- the last several years is that transcrip- fied. In that context, Michael Rosen- tors. The chair of this symposium will tional regulation of eukaryotic genes is feld (University of California, San be Cécile Rochette-Egly (IGBMC, a dynamic multistep process that Diego) will describe some new adap- Strasbourg) who will discuss how involves the ordered assembly of mul- tors that promote exchange of core- phosphorylation of nuclear retinoid tiprotein complexes of the basal tran- pressor and coactivator complexes receptors contributes to activation of scription machinery and of multiple required in transcriptional regulation. Continued on page 19

14 ASBMBToday NOVEMBER 2004

Coordinate Regulation of Transcription

Organizer: Cecile Rochette-Egly, C.U. de Strasbourg 2005 ASBMB Annual Meeting Held in conjunction with EB 2005 April 2-6, 2005, San Diego, CA

Additional Speakers will be Dynamic and Coordinated Integration of mRNA Processing chosen from the abstracts Recruitment of Activators and with Transcription submitted. Coregulators to Gene Promoters Coupling of transcription with mRNA processing and The estrogen receptor as a transcription factor chromatin Abstract Deadline: Chair, Frank Gannon, EMBL-Heidelberg Foundation for Chair, Stephen Buratowski, Harvard Medical School February 9, 2005 Research and Technology Coordination of pre-mRNA processing with transcription by Dynamics of preinitiation complex assembly on the RNA polymerase II regulatory regions of differentiation-induced genes David Bentley, Univ. of Colorado Health Sciences Ctr. Iannis Talianidis, Inst. of Molecular Biology and The polymerase and the poly(A) signal: mechanism of Biotechnology, FORTH Travel Awards Available for coupling processing with transcription in vitro and in vivo Undergraduates, Graduates, Structural and functional role of the human ARC/mediator co- Harold Martinson, Univ. of California, Los Angeles Postdoctoral Fellows, and activator in specific gene regulatory pathways Undergraduate Faculty. Anders M. Naar, Harvard Medical School

Identification of New Complexes Transcription Activators: More Information: that Regulate Transcription Integrators of Diverse Signaling ASBMB Meetings Office Transcriptional regulatory complexes Pathways 9650 Rockville Pike Chair, Joan Conaway, The Stowers Inst. Nuclear retinoid receptors phosphorylation and the Bethesda, MD 20814 Structural basis of transcription by RNA polymerase II transcription of retinoid-target genes Tel: 301-634-7145 Patrick Cramer, Univ. of Munich Chair, Cecile Rochette-Egly, C.U. de Strasbourg Fax: 301-634-7126 Genome-wide transcriptional regulatory strategies in Structural framework for signaling to the transcription Email: [email protected] development and disease factor Ets-1 Michael Rosenfeld, Univ. of California, San Diego Barbara Graves, Univ. of Utah, Huntsman Cancer Inst. Integration of signaling pathways by the ETS-domain transcription factor Elk-1 Andrew Sharrocks, The Univ. of Manchester

American Society for Biochemistry and Molecular BIology www.asbmb.org/meetings

Catalysis: Structure, Function, and Evolution Organizer: John A. Gerlt, University of Illinois, Urbana Champaign

he large numbers of protein The Prenyltransferase Superfamily: can change the reaction, often via sequences and structures deter- Evolution of New Reactions in the Iso- functionally promiscuous intermedi- T mined by genome sequencing prenoid Biosynthetic Pathway. Speaker: ates. Understanding Nature's strategies and structural genomics projects C. Dale Poulter, University of Utah for changing the reaction catalyzed by are providing biochemists with an Hold Only Loosely, But Don't Let an "old" active site template will pro- unprecedented information database for Go: Catalysis in the phosphomanno- vide important lessons for rational understanding how protein sequence mutase/phospho-glucomutase reac- design of "new"enzymes. This sympo- and structure deliver biological function. tion. Speaker: Peter A. Tipton, sium highlights three superfamilies for Now, instead of studying one enzyme at University of Missouri, Columbia which the structural basis for func- a time, enzymologists can study super- tional divergence is now understood. families of enzymes, with the conserved Radical Enzymes Mechanistic Diversity and Evolution elements of sequence and structure Chair: Wilfred A. van der Donk, Uni- of Function in the Vicinal Oxygen allowing Nature's strategies for catalysis versity of Illinois, Urbana-Champaign Chelate Superfamily. Speaker: Richard to be defined. This meeting addresses Long thought to be too unstable to be N. Armstrong, Vanderbilt University several topics that capitalize on important, many examples of radical Evolving, Designing, and Discovering sequence, structure, and evolution to intermediates in enzyme catalyzed reac- New Enzymes in the Enolase Superfam- identify and apply principles of catalysis. tion have now been discovered and ily. Speaker: John A. Gerlt, University of characterized. The generation, reactivity, Illinois, Urbana Champaign Intermediates in and properties of these intermediates Enhancing the Catalytic Promiscuity Enzyme Catalyzed have yielded to detailed structural and of Members of the Tautomerase Super- Reactions mechanistic investigation. This sympo- family. Speaker: Christian Whitman, Chair: Debra Dunaway Mariano, sium highlights the extraordinary detail University of Texas, Austin University of New Mexico that now can be achieved for character- Directed Evolution of Enzyme Func- Enzyme catalyzed reactions often izing the mechanisms of these reactions. tion. Chair: Frank M. Raushel, Texas involve the formation of transiently The Anatomy of a Radical Enzyme. A&M University stable intermediates whose fate is Speaker: Catherine L. Drennan, MIT Nature does not necessarily provide determined by the structure of the Ribonucleotide Reductase: Unnatural catalysts for known reactions with active site. Although such intermedi- Amino Acids to Interrogate Radical Ini- unnatural substrates or new reactions. ates are postulated to be intermediates tiation. Speaker: JoAnne Stubbe, MIT "Rational" design and combinatorial in nonenzymatic reactions, their insta- Mechanistic Studies on Cyclooxyge- evolution provide strategies for obtain- bility prevents detailed mechanistic nase and Lipoxygenase. Speaker: Wil- ing novel enzymes. This symposium and structural characterization. How- fred A. van der Donk, University of highlights recent advances in the in ever, these intermediates often can be Illinois, Urbana Champaign vitro evolution of enzymes to direct directly observed in active sites as a catalysis of "new" reactions. result of stabilizing interactions. This Natural Evolution of Molecular Diversity and Catalysis. symposium highlights recent achieve- Enzyme Function Speaker: Donald Hilvert, Swiss Federal ments in describing the structures and Chair: John A. Gerlt, University of Institute of Technology, Zurich reactivities of intermediates in phos- Illinois, Urbana Champaign Altering the Substrate Specificity of phoryl and prenyltransferases. The members of mechanistically Enzymes in the Amidohydrolase Super- Nucleophilic Substitution At Phos- diverse superfamilies catalyze different family. Speaker: Frank M. Raushel, phorus: Phosphorane Intermediates in overall reactions that share a common Texas A&M University Scaffolds Designed for Pushing and partial reaction. Studies of these super- Evolving Enzymes for Making Novel Metaphosphates in Scaffolds Designed families are providing mechanistic and Sugars and Glycoproteins. Speaker: for Pulling. Speaker: Debra Dunaway structural descriptions of how a small Chi Huey Wong, Scripps Research Mariano, University of New Mexico number of mutations in a progenitor Institute.

16 ASBMBToday NOVEMBER 2004

Catalysis: Structure, Function and Evolution Organizer: John A. Gerlt, University of Illinois at Urbana-Champaign 2005 ASBMB Annual Meeting Held in conjunction with EB 2005 April 2-6, 2005, San Diego, CA

Additional Speakers will be Directed Evolution of Natural Evolution of chosen from the abstracts Enzyme Function Enzyme Function submitted. Altering the substrate specificity of enzymes in the Discovering, designing, and evolving new enzymes amidohydrolase superfamily Chair, John Gerlt, Univ. of Illinois at Urbana-Champaign Chair, Frank M. Raushel, Texas A&M Univ. Abstract Deadline: Mechanistic diversity and the evolution of enzyme function February 9, 2005 Molecular diversity and catalysis Richard Armstrong, Vanderbilt Univ. Donald Hilvert, Swiss Federal Inst. of Technology, Zurich Enhancing the catalytic promiscuity of tautomerase superfamily members Evolving enzymes for making novel sugars Christian Whitman, Univ. of Texas at Austin Travel Awards Available for and glycoproteins Undergraduates, Graduates, Chi-Huey Wong, Scripps Research Inst. Postdoctoral Fellows, and Undergraduate Faculty. Intermediates in Radical Enzymes Enzyme-Catalyzed Reactions More Information: Mechanistic studies on the reaction of lipoxygenase Reaction intermediates in enzyme catalysis with arachidonic acids ASBMB Meetings Office Chair, Debra Dunaway-Mariano, Chair, Wilfred A. van der Donk, Univ. of Illinois 9650 Rockville Pike Univ. of New Mexico at Urbana-Champaign Bethesda, MD 20814 The prenyltransferase superfamily. Evolution of new The anatomy of a radical enzyme Tel: 301-634-7145 reactions in the isoprenoid biosynthetic pathway. Catherine L. Drennan, MIT C. Dale Poulter, Univ. of Utah Fax: 301-634-7126 Ribonucleotide reductases: regulation in S. cerevisiae Email: [email protected] Hold on loosely, but don’t let go: catalysis in the JoAnne Stubbe, MIT phosphomannomutase/phosphoglucomutase reaction Peter A. Tipton, Univ. of Missouri – Columbia

www.asbmb.org/meetings American Society for Biochemistry and Molecular BIology

2005 ASBMB Annual Meeting Held in conjunction with EB 2005 April 2-6, 2005 San Diego, CA Meeting Organizers Dennis R. Voelker, National Jewish Medical Research Center Cecile Rochette-Egly, IGBMC, Strasbourg and the 2005 ASBMB Program Planning Committee Meeting Themes Dynamics of Protein— Biochemistry and Molecular Biology of Lipids Protein Interactions (Bumping in the Night) Chair: Charles O. Rock, St. Jude Children’s Research Hospital Chair: Ben Margolis, HHMI, Univ. of Michigan Organelle Biogenesis and Dynamics DNA Replication and Interactive Repair Co-Chairs: Carla Koehler, UCLA and Danny Schnell, Univ. of and Recombinational Processes Massachusetts, Amherst Chair: Charles S. McHenry, Univ. of Colorado Health Sciences Proteolysis and Disease Center Chair: Charles Craik, Univ. of California, San Francisco Coordinate Regulation of Transcription Catalysis: Structure, Function, and Evolution Chair: Cecile Rochette-Egly, IGBMC, Strasbourg Chair: John A. Gerlt, Univ. of Illinois, Urbana-Champaign Interactions and Functions of Metabolic Regulatory Circuits Glycoconjugates Chair: M. Daniel Lane, Johns Hopkins Univ. School of Medicine Chair: Mark A. Lehrman, Univ. of Texas Southwestern Medical Center Genomes and Proteomes Chair: Andrew J. Link, Vanderbilt Univ. Integration and Organization of Signaling Pathways Education in the Biomolecular Sciences: Chair: Alex Toker, Beth Israel Deaconess Medical Center The Next Generation Co-Chairs: Judith G. Voet, Swarthmore College and Marion O’Leary, Minority Affairs Committee Symposia California State Univ. at Sacramento Chair: Phillip A. Ortiz, Empire State College American Society for www.asbmb.org/meetings Biochemistry and Molecular BIology

William Dowhan Selected for ASBMB-Avanti Award illiam Dowhan, John S. initiation of DNA replication (DnaA These observations W Dunn Professor of Biochem- mediated) in E. coli. Acidic lipids also are consistent with istry at the University of proved essential for the insertion of a the recent crystal Texas Medical Center in Houston will subset of E. coli membrane proteins. structure of LacY, receive the ASBMB-Avanti Award in The characterization of Dr. Dowhan's which reveals two Lipids. The Award which recognizes E. coli mutants completely lacking somewhat autono- outstanding research contributions in the zwitterionic phospholipid phos- mous domains, as the area of lipids alternates between phatidylethanolamine resulted in the would be expected ASBMB and the Biophysical Society. unambiguous demonstration of a phos- based on Dowhan's Dr. William Dowhan Previous recipients were Edward A. phatidylethanolamine requirement for studies. Dennis in 2000, Ronald N. McElhaney LacY function in living bacterial cells. Dr. Dowhan' s research over 30 years 2001, Christian R. H. Raetz 2002, Dowhan traced this phenomenon to a has established and defined the molec- Robert Bittman 2003, and in 2004 very specific failure of the N- terminal ular basis for new roles of lipids in a William L. Smith. The Award consists half of the LacY protein to diverse number of cell processes. His of a plaque, a stipend, and transporta- assemble properly in the absence of observations have expanded the num- tion and expenses to present a lecture phosphatidylethanolamine. The nor- ber of investigators who now consider at the ASBMB Annual Meeting, April mal topography of the first six trans- lipids as important to their studies. 2-6 in San Diego. membrane helices is actually reversed In summary, Dr. Dowhan' s science In the 1970s. Dr. Dowhan was the in the absence of phosphatidyl- is of the highest quality, and it is of first to purify to homogeneity several ethanolamine, even though normal fundamental importance to mem- key integral membrane enzymes of amounts of LacY are made and inserted brane and lipid biochemistry. He is a lipid biosynthesis when that was still a into the inner membrane. A subset of wonderful role model for younger sci- very difficult thing to do. This work membrane proteins are affected in this entists, and he freely shares his results validated the Kennedy pathway in E. manner, including several in the LacY with everyone in the field. He is fre- coli at the level of enzymology. He dis- class of permeases. LacY mis-folding quently invited to speak at national covered that phosphatidylserine decar- is reversed by restoring phos- and international meetings, and serves boxylase of E. coli contains an unusual phatidylethanolamine biosynthesis. on NIH study sections. pyruvate cofactor generated from a precursor protein by internal splicing. In the yeast system he was first to Regulation of Transcription continued … purify the phosphatidylcholine/phos- Continued from page 14 scription. He will describe a dynamic phatidylinositol exchange protein to transcription by controlling the asso- complex, the "mRNA factory," which homogeneity. Analysis of its N-termi- ciation/dissociation of co-regulators. carries out the processing of transcripts nal sequence led to the remarkable and influences the function of both conclusion that the SEC14 gene of Integration of mRNA the processing and transcription yeast, which is involved in protein processing with machineries through a growing num- secretion, is the structural gene for this transcription ber of regulatory interactions. Then, exchange protein. mRNA processing reactions (capping, Stephen Buratowski (Harvard Medical He was also first to make strains of E. splicing and polyadenylation) occur School) will describe RNA processing coli (and more recently of yeast) in co-transcriptionally. Though these factors associated with transcription which the content of major membrane reactions are biochemically distinct complexes and chromatin. Finally, phospholipids can be regulated in a processes, they are interlinked and so Harold Martinson (University of Cali- systematic manner by placing the influence one another's specificity and fornia, Los Angeles) will show how genes encoding key lipid biosynthetic efficiency. During this session, David poly(A)-dependent termination is cou- enzymes behind appropriate promot- Bentley (University of Colorado Health pled to transcription through the car- ers. This resulted in the demonstration Sciences Center) will discuss the link boxyl-terminal repeat domain of the of an acidic lipid requirement for the between mRNA processing and tran- largest RNA polymerase II subunit.

NOVEMBER 2004 ASBMBToday 19

Jack Dixon to Receive ASBMB-Merck Award ack E. Dixon, Professor and ety for Biochemistry and Molecular tion with Larry Zipursky at UCLA, the Dean of Scientific Affairs at Biology, Fellow of the American Acad- Dixon laboratory identified a novel J the University of California, emy of Arts and Sciences, election to receptor that is required for axonal San Diego School of Medicine, has the National Academy of Sciences, and guidance in the fly. Remarkably, the been selected to receive the 2005 the William C. Rose Award. gene encoding this receptor can ASBMB-Merck Award in recognition of Dr. Dixon has brought a strong undergo alternative splicing to gener- his outstanding contributions to chemical background and expertise in ate more than 38,000 different recep- research in biochemistry and molecu- molecular biology and molecular tor isoforms. This molecular diversity is lar biology. Recipients over the past genetics to his research investigations. likely to contribute to the specificity of five years have been Jack L. Strominger Early in his career, he was a leader in neuronal connectivity in 2004, Stephen Benkovic in 2003, research on the biosynthesis and post- Dr. Dixon's laboratory has also played Robert G. Roeder and Robert D. Korn- translational processing of polypeptide an important role in methods develop- berger who shared the Award in 2002, hormones. He adopted the tools of ment. Early in his career, he was a leader Avram Hershko and Alexander J. Var- molecular biology in research on the biosynthesis and shavsky who shared the Award in as they became post-translational processing of 2001, and Robert L. Baldwin in 2000. available in the polypeptide hormones. He adopted the Nominations must be originated by late 1970's, and his tools of molecular biology as they Society members, but the nominees laboratory was became available in the late 1970s, and need not be ASBMB members. The among the first to his laboratory was among the first to Award consists of a plaque, $5,000, use a synthetic use a synthetic oligonucleotides to iso- and transportation and expenses of the oligonucleotide to late a cDNA encoding peptide hor- recipient and spouse to the 2005 identify and clone mones that were expressed at low levels. Annual Meeting to present a lecture. cDNAs encoding Dr. Jack E. Dixon In addition his laboratory used the tools Following undergraduate study at the peptide hormones such as somato- of protein chemistry and mass spec- University of California, Los Angeles, statin, cholecystokinin, and neuropep- trometry to demonstrate previously graduate study at UCSB with Dr. tide Y. He subsequently became a unknown modifications of peptide hor- Thomas C. Bruice and postdoctoral pioneer and intellectual leader in the mones such as hydroxylation and a- training at UCSD with Dr. Nathan O. structure and function of the protein linked glycosylation. He also pioneered Kaplan, Dr. Dixon became a faculty tyrosine phosphatases (PrPases). in the use of mass spectrometry to make member at Purdue University. In 1991 Two recent studies from the Dixon disulfide bonds assignments in proteins. he was appointed Professor and Chair laboratory illustrate the breadth of Dr. The Dixon laboratory also developed of the Department of Biological Chem- Dixon's scientific contributions. Since glutathione S-transferase expression istry at the University of Michigan, and the discovery of the PTPase in the vectors which were easily cleaved by a year ago he became Dean of Scientific pathogen bacteria responsible for the proteases. These vectors have proven to Affairs and Professor of Pharmacology, plague, his laboratory has continued be of great utility in recombinant pro- Cellular and Molecular Medicine, its interest in the molecular aspects of tein expression. The original publica- Chemistry and Biochemistry at the bacterial pathogenesis. His laboratory tion describing these vectors has been University of California, San Diego. has recently demonstrated that a cited 1,274 times. Dr. Dixon was also While pursuing his research interests Yersinia effector protein (YopJ) is a pro- the first person to develop tools that with vigor, he has undertaken major tease that degrades ubiquitin-like pro- allowed the silencing of genes in administrative responsibilities with teins. YopJ homologs are found in Drosophila cell lines using RNA interfer- much success and is recognized nation- bacteria pathogenic to animals, plants, ence. This simple direct method has ally and internationally for his scien- and plant symbionts, suggesting that been widely used by others to map tific leadership. His honors include this mechanism of proteolysis is used metabolic pathways and to carry out election to the Institute of Medicine, to modulate a wide variety of signaling genetic screens to identify novel effector State of Michigan Scientist of the Year pathways present in the animal and proteins alternating signal transduction Award, President of the American Soci- plant kingdoms. Finally, in collabora- pathways.

20 ASBMBToday NOVEMBER 2004 HIGHEST QUALITYINOSITIDES LOWEST PRICES 14C 3H

Catalog Product Description Quantity ARC

3 ART 1298 12-Deoxyphorbol 13-phenyl acetate [20- H] AR5 µCi $999 3 ART 222 Glycerophoshoinositol [myo-inositol-2- H] ARC-235 µCi $999 3 ART-473 Glycerophoshoinositol [myo-inositol-2- H] 4,5 bisphosphate ARC-235 µCi $1199 3 ART-472 Glycerophoshoinositol [myo-inositol-2- H] 4 phosphate ARC-235 µCi $1199 ARC-232 Inositol, myo, [14C(U)] 5 µCi $479 ART-261 Inositol, myo, [1,2-3H(N)] 1mCi $729 ART-116 Inositol, myo, [2-3H(N)] 1mCi $649 ART-171 Inositol-1-phosphate, D-[inositol-2-3H] (1-IP) 5 µCi $299 ARC-233 Inositol-1-phosphate, D-[inositol-2-14C(U)] 5 µCi $299

ART-268 Inositol-3-phosphate, D-[inositol-2-3H] 5 µCi $359 ARCD-166 D-myo-Inositol 1-phosphate dipotassium salt, “Cold” 1 mg $179 ART-264 Inositol, scyallo, [2-3H(N)] 250 µCi $749 ART-872 Inositol 1,3,4,5 tetrakisphosphate D-[inositol-1-3H(N)] 5 µCi $629 ARCD-108 Inositol, myo D-1,4,5 triphosphate, “Cold” 1 mg $209 ARCD-109 Inositol, myo L-1,4,5 triphosphate, “Cold” 1 mg $199 ART-270 Inositol, 1,4,5-triphosphate, D-[inositol-2-3H(N)] (1,4,5-IP3) 5 µCi $579 ART-487 Phorbol-12,13-diacetate, [20-3H(N)] 50 µCi $309 ART-485 Phorbol-12,13-dibutyrate, [20-3H(N)] 50 µCi $299 ART-486 Phorbol-12-myristate-13-acetate [20-3H(N)] 50 µCi $319 ART-184 Phosphatidylinositol, L-α-[myo-inositol-2-3H(N)] PI [3H] 10 µCi $599 ART-183 Phosphatidylinositol 4,5-biphosphate 3 3 [myo-inositol-2- H(N)] PIP2[ H] 5 µCi $559

ARCD-131 Phosphatidylinositol 4,5-biphosphate (PIP2), “Cold” 1 mg $209 ARE-100 Phosphatidylinositol specific phospholipase C (PI-PLC) 5 units $339 ART-185 Phosphatidylinositol 4-phosphate, [myo-inositol-2-3H] 5 µCi $649 ART-1297 Prostatin [20-3H] [dPAC] 50µCi $999

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Jan-Åke Gustafsson Wins Bristol-Myers Squibb/Mead Johnson Award

an-Åke Gustafsson is the win- tion of the role of PPARs in lipid metab- son was elected ner of the twenty-fourth olism. And Dr. Gustafsson discovered a to the Swedish J annual Bristol-Myers Squibb/ second type of estrogen receptor as well Academy of Sci- Mead Johnson Nutritionals Freedom as a nuclear receptor that is important ences in 1997, to to Discover Award for Distinguished in cholesterol metabolism. the Swedish Acad- Achievement in Nutrition Research, Dr. Gustafsson received his Bachelor emy of Engineer- recognizing his efforts in pioneering of Medicine degree in 1964, his Ph.D. ing Sciences in the field of molecular nutrition, where in chemistry in 1968 and his M.D. 1998, became a he has played a pivotal role in discov- degree in 1971, all from the Karolinska foreign honorary Jan-Åke Gustafsson eries of how nuclear receptors in the Institutet. He was named a professor of member of the American Academy of cell mediate actions of nutrients and chemistry at the Institute in 1976, and Arts and Sciences in 2000 and a foreign hormones to regulate metabolism. Dr. to his current posts in 1979. In 1987, honorary member of the U.S. National Gustafsson is Professor of Medical he founded KaroBio AB, a biotechnol- Academy of Sciences in 2002. Nutrition and Chairman of the Depart- ogy company based at the Karolinska ment of Medical Nutrition as well as Institutet and initially supported by Current Research Director of the Center for Biotechnol- pension and government funds. Interests ogy of Novum, Karolinska University The author of more than 1,100 peer- The current research interests of the Hospital at the Karolinska Institutet in reviewed publications in scientific jour- Gustafsson Group fall mainly into the Stockholm, Sweden. nals, Dr. Gustafsson also has served or following two categories. They are, He helped establish a new field of currently serves on the editorial boards says Dr. Gustafsson: nutrition research and quickly became of a number of distinguished journals 1. Continued studies on the physio- a leader in that field. In the process, Dr. including the Journal of Molecular Medi- logical role of ERß and its pharmaceu- Gustafsson and his colleagues have cine, Molecular Endocrinology, Molecular tical applications. made critical contributions to our Pharmacology, Cancer Research, Cell Very excitingly, ERß agonists seem to knowledge of the mechanisms Metabolism and the International Journal be promising potential drugs against whereby certain nutrients and hor- of Oncology. He is also a member of the rheumatoid arthritis, inflammatory mones, among them fatty acids and International Advisory Board of the bowel disease (Wyeth-Ayerst), prostate vitamins A and D, regulate a variety of World Health Organization Center in disease including prostate cancer (Eli metabolic responses through their Oulu, Finland. Lilly), postmenopausal symptoms interactions with nuclear receptors. Among the many honors he has (Schering Germany), as well as depres- These interactions are fundamental to received during his career are: the Sved- sion. Since all these applications were their regulation of growth and metabo- berg Prize in chemistry in 1982, the Fern- predictable on the basis of our research lism and to their contributions to the ström Prize of the Karolinska Institutet in (published in MCB, PNAS and else- pathophysiology of diabetes and obe- 1983, the Anders Jahre Prize in 1992, the where), we now want to continue to sity. In addition, Dr. Gustafsson first Gregory Pincus Medal and Award of the study molecular mechanisms involved, described the three-domain structure of Worcester Foundation in 1994, the utilizing the pharamaceutical tools (ERß nuclear receptors, defined the function Söderberg Prize in Medicine in 1998, the agonists) now becoming available. We of these domains, and ascertained how European Medal of the British Society for also want to contribute to widening the the DNA-binding mechanism mediates Endocrinology in 2000, and the Fred pharmaceutical potential of ERß based certain activities in the cell including Conrad Koch Award from the Endocrine on our continuing characterization of cellular communication. He also was Society in the U.S. in 2002. He has served novel phenotypes of ERß KO mice, i.e. in the first to discover that fatty acids are as an adjunct member of the Nobel the lung, bladder and other tissues. Fur- natural activators of the peroxisomal Committee of the Karolinska Institutet, thermore, we are involved in identifying, proliferators activated nuclear receptors and was chairman of the Nobel Assem- if possible, human mutations of the ERß (PPAR), thus stimulating the investiga- bly of the Institute in 2002. Dr. Gustafs- Continued on next page

22 ASBMBToday NOVEMBER 2004

The Journal of Biological Chemistry Launches Papers of the Week

his past July, The Journal of high standard and we expect it will Recent Papers of the Week have Biological Chemistry (JBC) yield 50 to 100 papers each year.” included a report by Dr. Kevin Chen T launched Papers of the Week, Once selected, the paper is high- and colleagues on their generation of a new JBC Online feature that is lighted in the Table of Contents of the an MAO A/B knockout mouse line; a intended to recognize the top one per- issue of JBC Online in which it paper in which Dr. Xingzhi Xu dis- cent of submissions received by the appears. There is a link from the Table cussed how he and his colleagues journal. “This new feature was initi- of Contents to a summary of the paper established a link between a congenital ated to highlight and promote the that explains why the work was neurological disorder and DNA repair; remarkable contributions that our selected for this honor. The paper is and a report by Drs. Chulee authors make to the advancement of also included in a cumulative collec- Yompakdee and Joel A. Huberman on biochemistry and molecular biology,” tion of JBC Papers of the Week that can their discovery of a DNA sequence explained Dr. Robert Simoni, Stanford be accessed directly from the home involved in controlling the timing of University and deputy editor of JBC. page of JBC Online. DNA replication. The Papers of the Week are nomi- nated by JBC reviewers, Editorial Board Members and Associate Editors, who Lindquist Resigns As Whitehead President are asked to identify papers of unusual Dr. Susan Lindquist resigned as Presi- Dr. Lindquist is a pioneer in the interest and importance. “Our criterion dent of the Whitehead Institute at MIT, study of the stress response and pro- for selection as a Paper of the Week is effective November 1. The Board of tein folding. She concentrates on chap- only that each reviewer judge the paper Directors accepted the resignation “with erones (proteins that help others to to be among the top one or two papers extreme regret.” Dr. Lindquist has assume their proper shape) and prions that he or she will review for JBC in a headed the Whitehead since October (proteins with the property of causing year,” noted Dr. Simoni. “This is a very 2001. According to the Boston Globe, others to assume an alternative shape). during her tenure, Dr. Lindquist oversaw Focusing on bakers’ yeast as a model a “massive reduction in staff and budget organism, but also using fruit flies, the Gustafsson continued… to help create a separate science organi- plant Arabidopsis and Mammalian sys- Continued from previous page zation, the Broad Institute, whose head- tems, she employs a combination of gene involved in disease. Finally, we are quarters is now under construction next genetics, molecular and cell biology continuously exploring new molecular door.” The paper reports that the White- analyses, and biophysical methods, to mechanisms behind ERß action. head’s annual budget declined from understand the mechanisms of prion 2. Continued studies on the physiol- $130 million to roughly $50 million. propagation, generation of diversity ogy and pathophysiology of LXRß. The Whitehead Board stated that Dr. and human disease. We have observed several novel phe- Lindquist has been an extraordinarily Dr. Lindquist came to the White- notypes (unpublished) of LXRß KO effective president during a period of head in 2001 from the University of mice, indicating as yet undescribed transition unprecedented in the Insti- Chicago where she was the Albert D. physiological roles of this nuclear tute’s history. In the past three years, Lasker Professor of Medical Sciences in receptor. These phenotypes are now she successfully implemented the tran- the Department of Molecular Genetics being characterized in detail, including sition of the Whitehead/MIT Center and Cell Biology, and an Investigator underlying mechanisms. Our hope is for Genome Research to the newly in the Howard Hughes Medical Insti- that results from these studies will help established Broad Institute while pre- tute. She received her PhD in Biology in developing pharamaceutical use of serving opportunities for joint scien- from Harvard University in 1976, the LXRB targeted drugs currently tific programs between Whitehead and going to the University of Chicago as developed in many pharmaceutical the Broad. She also negotiated impor- an American Cancer Society Post-doc- industries for use in treating, for exam- tant improvements in the White- toral Fellow before joining the faculty ple, cardiovascular disease. head/MIT affiliation. there in 1977.

NOVEMBER 2004 ASBMBToday 23

BIOTECH BUSINESS NEWS

by John D. Thompson, Editor

‘Magnificent Seven’ Form Edinburgh Science Triangle t’s not that old western movie of the top 10 in European science and tish Centre for Genomic Technology and starring Yul Brenner, it is the technology excellence. Informatics (GTI) launched a £4.5 mil- I new Edinburgh Science Trian- Encompassing seven leading science lion project to support the commercial- gle, described as a triangle of excellence parks, all within a 45 minute drive, the ization of scientific breakthroughs, and for cutting edge science and technology Edinburgh Science Triangle (EST) is then the Korea Health Industry Develop- that has the capability of shaping the expected to bring a new dimension to ment Institute (KHIDI) established a future and a potential to contribute £750 the promotion of Scotland’s science Scottish office to manage a multimillion- million ($1,350 million U.S.) per year to excellence, according to Scottish Enter- pound investment in drug development Scotland’s economy, that has been estab- prise, Scotland’s main economic devel- research. South Korea’s KHIDI plans to lished in Scotland. opment agency. The new alliance is invest up to £18 million in Scottish drug Already home to more than 3,300 intended to showcase Scotland as a development projects over the next 9 world class researchers, the area has leading center in the appliance of sci- years. This makes Scotland the first coun- the potential to create 15,000 new ence and a world class location for try to take full advantage of South high value research jobs, across a companies and institutes seeking to Korea’s International Collaborative Pro- 500,000 square meter super-campus benefit from the expertise within EST. gram for Drug Development. with a development investment of All in all, the last week of September over £500 million ($900 million). was regarded as a good one for Scotland’s Launched in late September, the new life sciences sector last week, as in addi- Austrian Funding facility has the goal of ranking along- tion to EST the week saw two other side Cambridge and London as a top developments that promise to turn inno- Giant Emerges UK research region recognized as one vation into financial gain. First, the Scot- Austria has created a new agency to coordinate the funding of applied research in fields such as biotechnology Vioxx Recall May Bring Flood of Suits and nanotechnology, as well as to fos- The decision by Merck to halt Don S. Strong, an Oklahoma lawyer, ter interaction between Austrian sales of Vioxx, its blockbuster who filed a suit against Merck on the researchers and the international scien- painkiller, could lead to an day of the recall, as saying, “Our tific community. The Austrian Research onslaught of new lawsuits against lawsuit was in the works but the fil- Promotion Agency (FFG), which was the company according to The New ing was accelerated by the recall.” established by merging the Technology York Times. While he and other lawyers Promotion for Industry agency (FFF), The Times reported that lawyers appear to think that the recall will the Austrian Space Agency (ASA), the were predicting that hundreds and help their lawsuits, other experi- Bureau for International Research and perhaps thousands of new Vioxx enced product liability lawyers say a Technology Cooperation, and the lawsuits are likely to be filed, many new wave of litigation may not nec- Technology Impulse Society, is of them class actions that aim to essarily be more distracting for expected to be a giant in the country’s represent large groups of Vioxx users Merck than the suits that are already research funding, with a budget that who have taken the drug for working their way through the could be as high as 300 million euros a extended periods. It said that radio courts. Should the Vioxx cases fol- year, according to media reports. advertisements seeking plaintiffs low the pattern of other major prod- The creation of the FFG is part of an were being broadcast and some suits uct liability battles, a surge in ongoing reorganization of Austrian sci- were filed almost immediately after lawsuits could well encourage court- ence funding bodies, which are being Merck’s recall announcement on ordered consolidation of the litiga- merged, scaled up, and streamlined as September 30. The paper quoted tion, hastening its resolution. the country seeks to adapt to changes across Europe.

24 ASBMBToday NOVEMBER 2004

BIOTECH BUSINESS NEWS

Tularik Acquisition Enhances Amgen’s Research Organization mgen Inc., the world’s largest executive vice president research and “We are truly looking forward to biotechnology company, has development of Amgen. “We welcome being a part of Amgen,” said Tularik A completed the acquisition of the Tularik staff into our organization founder and CEO David V. Goeddel, Tularik Inc., a pioneer in drug discovery and are confident that our combined who recently received The Economists’ related to cell signaling and the control research capacity will help patients by Annual Innovation Prize Award in Bio- of gene expression. Final regulatory advancing important treatments for science for gene cloning and the approvals were received in June and serious diseases.” expression of human proteins. Tularik stockholders approved Amgen’s Pursuant to the merger agreement “Tularik’s research engine is a rare acquisition of the company during a announced on March 29, 2004, asset and a great strategic fit. Tularik has special meeting held yesterday. Amgen will exchange Tularik com- a strong team of scientists who share “The completion of this acquisition mon stock for Amgen common stock our desire to develop important new underscores our commitment to scien- in a tax-free transaction. Tularik stock- therapeutics in inflammation, meta- tific excellence and innovation holders will be entitled to 0.451 shares bolic diseases, and oncology. Amgen through the expansion of our internal of Amgen common stock for each and Tularik have complementary chem- drug discovery research capabilities,” share of Tularik common stock held. istry expertise and compound libraries said Roger M. Perlmutter, M.D., Ph.D., Any fractional shares will be paid in that together strengthen and broaden cash. A total of approximately 24 mil- our discovery capabilities,” said Dr. Perl- lion Amgen shares will be issued as mutter, who along with Dr. Goeddel is Strategies to Support the consideration. an ASBMB member. Bio/Pharma Value Chain The need to overcome the pharma- ceutical industry’s pipeline productiv- FDA Eases Rules on Drug Manufacturing ity crisis is forcing the genomics Drug makers will not need regula- Some critics said the changes innovators and their partners to tory approval for every change in amounted to decreased regulation reshape their portfolio management, their manufacturing processes under that could harm patients if problems according to DataMonitor, a consult- new guidelines designed to prevent were not uncovered before medi- ing firm that specializes in market supply disruptions, U.S. health offi- cines were released to the public. Dr. research. In a report released in early cials said September 30. Companies Sidney Wolfe, head of Public Citi- October, the company states that new can skip the prior approval require- zen’s Health Research Group, a con- asset allocation strategies and valua- ment if they have developed adequate sumer group, was quoted by Reuters tion methodologies are needed to tests and procedures to show certain as saying, “I don’t think it’s a good support the evolution to a new busi- changes will not affect product safety idea. From a patient perspective, it is ness model emphasizing investment or effectiveness, the Food and Drug questionable and intermittently in technological diversification. A Administration said in a report. dangerous.” new wave of innovation is focusing The modification is part of a just- Health and Human Services Secre- on gene functionalities, population completed, two-year effort to overhaul tary Tommy Thompson, however, genomics, and pharmacogenomics. regulation of pharmaceutical manu- said in a statement that the FDA’s Drug developers should continue facturing, a major issue for drug mak- plan would ensure “consistently integrating well-defined genomics ers. In the past, Schering-Plough high quality” for the U.S. drug sup- assets into their supply chains, work Corp., Eli Lilly and Co. and other com- ply. The FDA said the new measures to maximize successful target valida- panies had trouble meeting federal would help drugs get on the market tion and optimize alliance networks production standards and faced delays quicker and prevent supply short- to ensure asset co-evolution and in the approval of new medicines. ages or disruptions. diversification.

NOVEMBER 2004 ASBMBToday 25

NIH NEWS

Steven McKnight Among Winners of NIH Director’s New Pioneer Award Recipients teven McKnight,* Professor tion factors, the regulatory proteins that Joseph McCune, and Chairman, Department switch genes on and off, at a biochemi- J. David Glad- S of Biochemistry, University of cal level with keen attention to biologi- stone Institutes, Texas Southwestern Medical Center, cal relevance. He is a member of the San Francisco; Dallas, is one of the first five researchers National Academy of Sciences and Chad Mirkin, selected to receive the NIH Director’s serves on the Scientific Advisory Board Northwestern Pioneer Award, a program designed to of the Howard Hughes Medical Institute University; Rob support individual scientists and and the Board of Trustees of the Phillips and thinkers with highly innovative ideas Carnegie Institution of Washington. Steven Quake, Dr. Steven McKnight and approaches to contemporary chal- To inaugurate this new program, the both of the Cali- lenges in biomedical research. A central NIH will provide $500,000 in direct costs fornia Institute of Technology; and component of the NIH Roadmap for per year for five years to each Pioneer Sunney Xie, Harvard University. Medical Research, the Director’s Pio- Award recipient, allowing them the time The nine recipients represent a neer Award was established in January and resources to test far-ranging ideas broad spectrum of scientific disciplines 2004 to encourage exceptional with the potential to make extraordinary including quantitative and mathemat- researchers and thinkers from multiple contributions to medical research. ical biology, pathogenesis, epidemiol- disciplines to conduct high-risk, high- The other recipents of the award ogy and translational clinical research, impact research related to the improve- are: Larry Abbott, Brandeis University; molecular and cellular biology, inte- ment of human health. George Daley, Children’s Hospital grative physiology, instrumentation The McKnight laboratory seeks to Boston, Boston; Homme Hellinga, and bioengineering. understand the regulation of transcrip- Duke University Medical Center; *ASBMB member. $216 Million To Math, Science Education Improvement The National Science Foundation achievement and offering challeng- This year’s MSP funding comes in has announced the award of $216.3 ing curricula at all grade levels. four forms: comprehensive awards; million in funding for the second year “The Math and Science Partnerships targeted awards; research, evalua- of its innovative Math and Science are about reinvigorating mathematics tion and technical assistance Partnerships to improve mathematics and science instruction and strength- awards; and a Prototype Institute and science education in United ening curriculum across the United Partnership award. States and Puerto Rico schools. States,” said Dr. Judith A. Ramaley, The comprehensive awards specifi- Math and Science Partnerships who leads NSF’s Directorate for Educa- cally marry institutions of higher grants unite elementary and second- tion and Human Resources. “These education and stakeholder organiza- ary teachers and administrators with awards are an investment in the talent tions with elementary and secondary collegiate science, technology, engi- pool of the nation’s future scientists, schools to continuously improve stu- neering and mathematics faculty and engineers and mathematicians.” dent achievement from the earliest representatives from stakeholder The awards will directly impact at grades through 12th grade. institutions. The partnerships focus least 2.85 million students nation- This year’s MSP participants and on enhancing the quality, quantity wide and in Puerto Rico who learn in FY2003 awards can be found at: and diversity of science and mathe- urban, rural, suburban and tribal http://www.nsf.gov/od/lpa/news/03/ matics teachers, raising student nation schools. pr03112.htm#attachment

26 ASBMBToday NOVEMBER 2004

Career Opportunities

Three Molecular Biology NUTRITION DIRECTOR POSITIONS candidate will design and conduct Postdoctoral Positions at National AVAILABLE Physicians Committee experiments, present his/her work at Renewable Energy Lab, Golden, CO. for Responsible Medicine national meetings, prepare scientific manuscripts, and obtain research The candidates will be involved in Clinical Research Director and funding. projects related to the development of Nutrition Director for NIH-supported Applicants should have Ph.D. or H2-photoproducing algae. The first non-profit organization in M.D. and a strong background in project is developing molecular Washington, DC. The Clinical molecular and cellular biology and engineering techniques to enhance the Research Director will oversee mouse research. Applicants should also O2 tolerance of hydrogenases in algal nutrition-related human clinical trials have strong organizational skills, platforms (see www.eere.energy.gov/ and literature reviews and must have excellent communication skills and hydrogenandfuelcells for more research interest and experience. The ability to work independently. information). Nutrition Director will supervise Interested applicants should send The two other projects are related to, nutrition education, advocacy, and their curriculum vitae, a letter of respectively, the investigation of global outreach and must have experience interest with specific research goals, gene expression of algal cultures under with vegetarian nutrition and program and names of three references to: H2-producing conditions, and the supervision. A doctoral-level degree, identification of factors that interpersonal skills, and writing skills Elneda Boyd specifically regulate expression of the are essential. Send letter of interest and Section of Pulmonary & Critical Care algal hydrogenase (see Posewitz et al., CV to Physicians Committee for The University of Chicago Plant Cell 16, 2151-2163, 2004 and Responsible Medicine [email protected], 5841 S. Maryland Ave., MC 6076 Posewitz et al., J. Biol. Chem. 279, 5100 Wisconsin Avenue, Suite 400, Chicago, IL. 60637 25711-25720, 2004). The candidates Washington, DC 20016, fax: 202-686- [email protected] should have molecular biology 2216. EOE. experience and preference will be The University of Chicago is an given to those who have worked with Research Associate Affirmative Action/Equal Opportunity the green alga, Chlamydomonas Employer. reinhardtii. Experience with The Section of Pulmonary and hydrogenase systems in other Critical Care Medicine at the organisms is a plus. The candidates are University of Chicago is seeking a also required to have good dynamic highly-motivated Research communication skills in English. Associate (Instructor/Assistant Research will be in collaboration with Professor) to be part of a successful Mike Seibert and Maria Ghirardi. Send research team studying the role of a cover letter stating your research costimulatory molecules in Th2 interests, a CV and the contact responses in both mice and humans. information for three professional These studies include many aspects of Place your Career references to Beverly Maestas immunological regulation, cell [email protected] function, and animal physiology and Ads in ASBMB Today Req.# 5900-5094. Salaries are highly pathophysiology using various Recruitment advertising is competitive, genetically altered mouse models. available in ASBMB Today for $12 Further, the successful candidate will per line, 10 line minimum. Copy is due by the first of the month prior NREL is an equal opportunity employer supervise technical staff in the to the issue month. For recruitment committed to diversity. recruitment and evaluation of volunteers for translational studies. advertising information call The position offers a unique Veronica at FASEB AdNet, 800-433- 2732 ext. 7791 or 301-634-7791, opportunity to a motivated individual email: [email protected] to participate technically and Display space is also available for intellectually in cutting edge those desiring greater visibility. biomedical research. The successful

NOVEMBER 2004 ASBMBToday 27

Calendar of Scientific Meetings

NOVEMBER 2004 MARCH 2005 4th International Congress on Autoimmunity CSBMCB Sponsored Meeting on Cellular Dynamics November 3–7 • Budapest, Hungary March 16-20 2005 • Banff Centre, Banff Alberta Deadline for Receipt of Abstracts: June 20, 2004 This meeting, set in Banff National Park, will feature cutting- Contact: 4th International Congress on Autoimmunity Kenes edge sessions on Nuclear structure, Organelle Inheritance, International—Global Congress Organisers and Association Imaging Technologies, Protein Folding, mRNA localization, Management Services,17 Rue du Cendrier, PO Box 1726, Organelles of the secretory pathway and Systems approaches CH-1211 Geneva 1, SWITZERLAND to Cell Biology. Keynote Speaker is Günter Blobel. Ph: +41 22 908 0488; Fx: +41 22 732 2850 Email: [email protected] Email: [email protected] Website:http://www.csbmcb.ca/2004Meeting/index.ht Website: www.kenes.com/autoim2004

American Association of Pharmaceutical Scientists APRIL 2005 AAPS Annual Meeting and Exposition American Society for Biochemistry and Molecular November 7–11 • Baltimore, Maryland Biology Annual Meeting in Conjunction with EB2005 Ph: 703 243 2800; Fx: 703 243 9650 April 2 – 6 • San Diego Website: www.aapspharmaceutica.com/meetings/futuremeetings/ Nobel Laureates Michael S. Brown and Joseph L. Goldstein will open the ASBMB Annual Meeting with the Herbert First Latin-American Protein Society Meeting Tabor/Journal of Biological Chemistry Lecture. November 8–12 • Hotel do Frade, Rio de Janeiro, Brazil Contact: ASBMB 2005, 9650 Rockville Pike, Bethesda, MD Sponsored by The Protein Society, The Wellcome Trust, and 20814-3008; Ph: 301-634-7145; Email: [email protected] Brazilian research funding agencies. Website: www.asbmb.org/meetings For more information: Dr. Alberto Spisni Brazilian Synchrotron Light Laboratory, Campinas, Brazil, The 46th ENC Experimental Nuclear Magnetic Resonance and Dept. Experimental Medicine, University of Parma, Italy April 10–15 • Rhode Island Convention Center, Providence, Caixa Postal 6192 - CEP 13084-971, Campinas, SP, Brazil Rhode Island Ph: +55 19 3287-4520; Fx: +55 19 3287-4632 Contact: ENC, 2019 Galisteo Street, Building I Email: [email protected]; Website: www.lnls.br/lapsm Santa Fe, New Mexico 87505 (USA); Ph: 505-989-4573 Fx:(505-989-1073; E-mail: [email protected] Second National Meeting of the American Society for Website: www.enc-conference.org Matrix Biology Nov 10–13 • San Diego, California MAY 2005 Contact: ASMB, 2019 Galisteo Street, Building I-1, Santa Fe, NM 87505; Ph: 505 989-4735; email: [email protected] From Gene to Genome: Heredity and Society Website: http://www.asmb.net May 26 - 28 • Palais de Congrès, La Grande Motte, France The half-century long success story of genetics and genomics DECEMBER 2004 has had and will continue to have a profound impact on society. It is time to recall how the science of genetics has American Society for Cell Biology, 44th Annual Meeting evolved, and modified several fields of society such as medi- cine, law, ethics, behaviour. Taking advantage of the 40th December 4-8 • Washington, DC anniversary of the Nobel prize awarded to a team from the Ph: 301-347-9300; Fx: 301-347-9310 Pasteur Institute, the French Society for Genetics has invited Website: http://www.ascb.org/ prominent geneticists, historians and philosophers to address these issues. Contact: Christophe Schwob Ph: +33 4 95 09 38 00; Fx : +33 4 95 09 38 01 Email : [email protected] Website: www.genetogenome.org

28 ASBMBToday NOVEMBER 2004

Department Heads Take Note:

JUNE 2005 7th Annual Plant Sciences Institute Symposium; ASBMB Offers Meristems 2005 June 2-5 • Iowa State University, Ames, Iowa Free Membership to Abstracts due April 1, 2005; Registration Deadline May 2, 2005 Student Travel Grants: Applications due April 1, 2005 Contact: Plant Sciences Institute Symposia, Symposium Office, New Ph.D.s 3208 Molecular Biology Building, Iowa State University, Ames, Iowa 50011-3260; Ph: 515-294-7978; Fax: 515-294-2244 ASBMB is now offering a free one-year Email: [email protected] Associate membership to all students who Website: www.bb.iastate.edu/~gfst/phomepg.html have, within the past year, earned a Ph.D. degree in the molecular life sciences or JULY 2005 related areas. 30th FEBS Congress — 9th IUBMB Conference, 2005 ASBMB implemented this program as a The Protein World; Proteins and Peptides: way to recognize the significant Structure, Function and Organization; accomplishment of earning the Ph.D., and to Science is Fun: A Conference for Your Creativity provide new Ph.D.s with something tangible and of economic value. Membership in July 2–5 • Budapest, Hungary ASBMB brings with it a free subscription to Contact: Ms. Franciska Morlin, Chemol Travel Congress Dept. the online versions of the Journal of Biological H-1366 Budapest, P.O.Box 28, Hungary Ph:+36-1-266-7032, Fx: +36-1-266-7033 Chemistry and Molecular and Cellular Email: [email protected]; www.febs-iubmb-2005.com Proteomics, as well as subscriptions to The Scientist and the Society’s magazine, ASBMB BioScience2005 - From Genes to Systems Today, discounts on other publications, and a July 17-21 July • Glasgow, UK host of other benefits. Focus topics for the meeting: Cell architecture: from structure to func- The Society is asking department chairs tion; The nucleus: chromatin, recombination and repair; Cellular infor- to provide ASBMB with the names and mation processing; Proteins in disease; Stem cells and development. Plenary speakers include: Robert J. Lefkowitz, Wolfgang Baumeister, P. addresses of each new Ph.D. recipient from Leslie Dutton, Walter Kolch, and David Stuart. Poster abstract deadline: their institutions. Upon receipt of this April 15, 2005, Early registration deadline: May 23, 2005 information, we will write the new Ph.D.s to For more information: BioScience2005, Biochemical Society, congratulate them on their accomplishment c/o Commerce Way, Colchester, Essex CO2 8HP and offer the free one-year membership in Ph: +44 (0)1206 796351; Fx : +44 (0)1206 798650 ASBMB. Names and addresses of the new Email: [email protected]; www.BioScience2005.org Ph.D.s should be sent to:

SEPTEMBER 2005 Membership at ASBMB American Society for Biochemistry Strategies for Engineered Negligible Senescence & Molecular Biology (SENS), 2nd Conference 9650 Rockville Pike Bethesda, MD 20814 September 7-11 • Queens’ College, Cambridge, England Email: [email protected] Conference organizer: Aubrey de Grey Email: [email protected]) This is an ongoing project; please advise us Website: http://www.gen.cam.ac.uk/sens2/CSBMCB whenever a student in your department earns the Ph.D., so that we can make this free membership offer to him or her.