constituent society of faseb american society for ......munication between the nih and the research...

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Constituent Society of FASEB

A M E R I C A N S O C I E T Y F O R B I O C H E M I S T R Y A N D M O L E C U L A R B I O L O G Y

OCTOBE R 2005OCTOBE R 2005 w w w . a s b m b . o r g

Constituent Society of FASEB

Held in conjunction with EB2006

NIH Conflict ofInterest Regs Revised

SEE PAGE 30 FOR NEW

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f e a t u r e s6 NIH Conflict of Interest Regs Revised

7 Emerging Staph Strains Increasingly Deadly

8 In Ed Dennis’ Lab Lipids Take the Spotlight

12 How Plants Disarm Toxic Effects of Sunlight

13 So You Think You Know Biochemistry History

14 ASBMB to Honor Thomas Cech

16 Biochemistry and Molecular Biology of Lipids

18 Glycobiology and Extracellular Matrix

20 Chemical Genetics and Drug Discovery

22 Genome Dynamic : Replication, Repair and Recombination

23 Richardson to Receive Tabor/JBC Award

24 More Women Receive Ph.D.’s, but Female Senior Faculty Rare

25 New Look for the JBC

26 Brain Fatty Acids Linked to Depression

27 New Understanding of DNA Repair

30 IOM Sees Flaws in Bioterrorism Protection

d e p a r t m e n t s4 News From the Hill

5 Evolution Watch

6 NIH News

21 ASBMB Reminiscences

28 Biotech Business

32 Calendar

A M E R I C A N S O C I E T Y F O R B I O C H E M I S T R Y A N D M O L E C U L A R B I O L O G Y

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O N T H E C O V E R :

28 Sales ofBiogenerics in U.S. ,Europe Expected toSoar

8

OCTOBER 2005, Volume 4, Issue 7

5

BRONZE AWARD WINNER 2003

AWARDS OF EXCELLENCE:MOST IMPROVED MAGAZINE

COLUMNS & EDITORIALS

DESIGN & LAYOUT

ASBMBToday OCTOBER 20052

A S B M B C o u n c i l

OfficersJudith S. Bond PresidentBettie Sue Masters Past-PresidentPeggy J. Farnham SecretaryKenneth E. Neet Treasurer

Council MembersWilliam R. Brinkley CouncilorJoan W. Conaway CouncilorRobert A. Copeland CouncilorLila M. Gierasch CouncilorFrederick P. Guengerich CouncilorWilliam J. Lennarz CouncilorPeter J. Parker Councilor William S. Sly CouncilorWilliam L. Smith Councilor

Ex-Officio MembersGeorge M. CarmanChair, Meetings CommitteeCecile Rochette-EglyDennis R. VoelkerCo-chairs, 2005 Program CommitteeJ. Ellis BellChair, Education and ProfessionalDevelopment CommitteeJuliette BellChair, Minority Affairs CommitteeWilliam R. BrinkleyChair, Public Affairs Advisory CommitteeChristopher K. MathewsChair, Publications CommitteeHerbert TaborEditor, JBCRalph A. BradshawEditor, MCPEdward A. DennisEditor, JLR

ASBMB Todayis a monthly publication

of The American Society for Biochemistry and Molecular Biology

Editorial Advisory BoardIrwin FridovichRichard W. HansonBettie Sue MastersJ. Evan SadlerRobert D. Wells

CommentsPlease direct any comments or questionsconcerning ASBMB Today to:

John D. ThompsonEditor, ASBMB Today9650 Rockville PikeBethesda, MD 20814-3996Phone: 301-634-7145; Fax: 301-634-7126E-mail: [email protected]

For information on advertising contact FASEB AdNet at 800-433-2732

ext. 7157 or 301-634-7157, or email [email protected].

L E T T E R S

Fo l lowing is a letter froma member to ASBMBPres ident Jud ith Bond insupport of her letter toPres ident Bush (seeart ic le on page 4 of theSeptember issue of ASBMBToday ) concern ing h iscomments on the teach ingof “ Inte l l igent Des ign” insc ience c lassrooms . Dr.Bond ’s rep ly fo l lows .

Dear Dr. Bond,Thank you for the letter you wrote

to President Bush in response to hiscomments on the teaching of Intelli-gent Design. I fully support the posi-tion that ID is not science and shouldnot be taught as such. I hope to seeASBMB and FASEB play a greater rolein educating the public and politiciansabout this important issue, especiallyin communicating the fact that theconcept of biological evolution is not ascientific controversy and is supportedby overwhelming evidence.

Thanks again for your efforts.Mark Hahn

ASBMB member (since 1994)Woods Hole Oceanographic Institution

Dear Dr Hahn,Thanks for your message. We agree

this is an important issue in our soci-ety, and would like to play a role inreaching the public on the points youarticulated so well. Among otherthings, we will be holding sessions atour centennial meeting in San Fran-cisco to help our members bring upthe issues in public settings and withpoliticians.

Judith BondASBMB President

Evolut ion NotTaught ProperlyDear Editor:

I am contacting you about an articleby Peter Farnham in the August 5 issueof ASBMB Today. He reports on a futureASBMB symposium on teaching Evolu-tion. On the bottom of page 10 and thetop of page 11 is the following state-ment: “However, Justice Antonio Scalia,in a dissenting opinion. left the dooropen to teaching alternative theories ofhow life began on earth.” This sentenceis in the context of the attacks on theDarwin’s Theory of Evolution. But theTheory of Evolution has NOTHING todo with how life began. In fact, in aMarch 29, 1863 letter to J. Hooker, a fel-low scientist, he states: “It is mere rub-bish thinking at present of the origin oflife; one might as well think of the ori-gin of matter.” This letter was writtenafter the publication of Origin of Species.

A major problem that we have infighting Intelligent Design people isthe fact that Evolution is not taughtproperly in our schools, as emphati-cally demonstrated by the above. Thisshould be part of the program of theplanned Symposium.

Bernard F. Erlanger, Ph.D.Columbia University

Member Supports AS BM BStand on ‘ Intel l igent Design’

T e l l U s W h a tY o u T h i n k

Letters should be sent to the editor,John Thompson, at the addressfound at left. Letters must be signedand must contain the writer’s addressand telephone number. The editorreserves the right to edit all letters.

OCTOBER 2005 ASBMBToday 3

From the Desk of the Pres ident :

Toni as rigorous, fair, creative, and abuilder of ‘bridges’—particularly at theinterface of basic science and medicine.Dr. Elias Zerhouni described Toni as a‘Renaissance Man,’ with a ‘can do,’pragmatic spirit who brings intelligenceand creativity to the CSR directorship.

The CSR is the major portal of com-munication between the NIH and theresearch external community, and itsmission is to fund the most promisingscience. The CSR reviews 90% of thegrant application (~ 80,000 grants peryear) that NIH considers for funding.Approximately 15,000 scientists serveCSR through reviewing activities. It isthe heart of the NIH peer-review system.

Toni’s vision is to increase the trans-parency, and enhance communicationand efficiency of the peer-review system;shorten the review cycle and recruitexcellent reviewers. He plans to examineand institute changes in the review ofproposals to align the NIH with changes

in the world byfocusing, for exam-ple, on chronic aswell as acute dis-eases, and payingattention to thebasic mode and cul-ture of research inour institutions. Aswe all know, institut-ing changes will be adaunting challenge.As Dr. Zerhouni cau-tioned, “Embracingchange is likeembracing a cactus”.

The good newsis that Toni bringsinsight and experi-

ence of an experimental scientist andacademic administrator to the NIH peer-review system. He bringsenergy, creativity, a pragmatic atti-tude, and determination to make thesystem better.

The bad news is that he is arrivingat a time when legislators are notlikely to raise the NIH budget to evenmeet the costs of inflation. Fundingto combat terrorism, fight wars andrecover from national disasters maywell be diverted from allocations forinvestigator initiated research. Thereare many concerns in the scientificcommunity about whether the newstructure of the CSR review sections isserving the needs of the scientificcommunity, new investigators, pro-ductive scientists, and importantareas of research (e.g., structural biol-ogy, bacterial pathogenesis, manyaspects of fundamental research).Many feel that critical areas ofresearch are slipping between thecracks of the ‘new review system’.Those of us who served on study sec-tions of the past are wary about someof the new practices in the operationof the study sections, such as exces-sive reliance on ad hoc members, andlack of experienced scientists toreview interdisciplinary projects, aswell as the low percentile of grantsbeing funded.

Toni has his work cut out for him.It will be our responsibility to workwith him.

Note: Toni’s wife Meredith Bond (norelation to Judith Bond or James Bond) isalso a member of the JBC editorial board.

Judith BondPresident, ASBMB

ntonio Scarpa, MD/PhD, wassworn-in as the new Directorof the National Institutes of

Health CSR on September 15. Tonireceived his MD and PhD in Pathologyat the University of Padua in 1966 and1970, respectively. He did postdoctoralwork at the Weizman Institute of Sci-ence in Israel, and then rose throughthe academic ranks in biochemistryand biophysics at the University ofPennsylvania. In 1986, he went toCase Western Reserve University asProfessor and Chair of Physiology. Hehas many years of experience as a pro-ductive research scientist in the area ofcellular and molecular mechanisms ofion transport and homeostasis, and hehas served the profession as a memberof study sections and as an editor ofjournals and books.

At the swearing-in ceremony, Dr.Story Landis, Director of NINDS, andpreviously a Chair at Case, described

New Director of the Center for Scient i f ic Review (CS R) at N I H: Toni Scarpa

A

Meredith Bond, Professor and Chair of Physiology at the University ofMaryland Biotechnology Institute, and wife of Dr. Scarpa; ToniScarpa,Director of CSR; Judith Bond, President ASBMB.

Dr. Judith Bond

including that Congress review thenumber of NIH institutes (however,while the report recommended thatconsideration be given to merging acouple of institutes, it also recom-mended that Congress merely set up aprocess to study the issue; it specifi-cally cautioned against a wholesalereorganization).

Given this new “power of thepurse,” this provision as well as othersin the bill would result in the NIHDirector receiving a great deal of newpower at the expense of the institutedirectors. While this power would belimited in certain ways, so far, there islittle enthusiasm in the scientific com-munity for the proposal

What’s the Hurry?Barton is most eager to pass an NIH

reauthorization bill this year—it is oneof his top priorities—and it is a fairquestion to ask why (Barton’s commit-tee has held eleven hearings on thetopic). While reauthorizing NIH isimportant in itself, there appears to bemore at stake, however. How Congressdivides power over federal agencies is amajor factor.

Barton is very concerned that overthe years, congressional authorizingcommittees have yielded power to theappropriations committees. In NIH’scase, the last time it was authorizedwas more then ten years ago, and sincethat authorization bill expired, appro-priators, who are ideally supposed toconcern themselves with money, havebeen implementing policy and organi-zational changes that are usually thepurview of the authorizing commit-tees. In short, Barton is tired of thisstate of affairs, and thus wants torestore authorization power to thecommittees where it belongs.

N E W S F R O M T H E H I L L


by Peter Farnham , CAE , ASBMB Pub l i c A f fa i rs O f ficer

Barton’s top aide working thisissue, Cheryl Jaeger, has been meet-ing with the scientific community inan effort to line up support for thebill. Jaeger has stated in several pub-lic discussions of the draft bill thatBarton is willing to work with thescientific community and is willingto be flexible on many aspects of it,but only up to a point. She haspointedly noted that Barton is notinterested in “legislating the statusquo” and the scientific communityhas to keep this in mind. However,she also has stated that Barton is nottrying to harm NIH, but rather, tohelp demonstrate the valuable workthe agency is conducting and toensure that public money spent atNIH is a wise investment.

Can This Bill Pass?Looking ahead, one sees a rocky road

for the Barton bill. First and foremost,the bill has not even been introducedin the House yet. And, based on thepublic response so far to the discussiondraft, it is likely to have little if anysupport once it is.

Second, there is no indication that asimilar bill will be introduced in theSenate any time soon. In addition, theSenate will be focusing on twoSupreme Court vacancies this fall, aswell as finishing up its versions ofappropriations bills (the Senate is farbehind the House in this importantwork; although the House has passedall its appropriations bills, so far onlytwo have become law). Finally, effortsto fix blame for the devastating effectsof Hurricane Katrina and its chaoticaftermath will no doubt take up a lotof valuable time between now and theend of the year.

N I H Reauthorizat ion Effort Due This Fal louse Energy and CommerceChairman Joe Barton (R-TX)has made it clear in recent

weeks that he intends to introduce andpass an NIH reauthorization bill in thisCongress. As a first step, his staff begancirculating a “discussion draft” of sucha bill in July. A second version, reflect-ing some—but not all—commentsreceived from members of Congressand the science community, has beenmaking the rounds in Washingtonsince late August. Unfortunately, thevery items in the bill to which Bartonseems most committed are also the ele-ments to which the science commu-nity is most opposed.

One of these elements is a majorreorganization of the NIH. A few wordsof background—each year, when theNIH appropriations bill is considered,the individual institutes and centersare considered separately for purposesof appropriating money. Under theBarton plan, the institutes would bedivided up into two main groups—“mission specific” and “scienceenabling” institutes. Congress wouldnow appropriate money to these twomain groups, and leave it up to theNIH Director (within certain limits) todistribute the money to the institutes.Further, the number if institutes andcenters would be fixed at no morethan 24 (a copy of the Barton bill willbe on the ASBMB home page underthe “What’s New” column throughoutSeptember and October).

Barton cites as authority for thisreorganization a July 2003 report,Enhancing the Vitality of the NationalInstitutes of Health: OrganizationalChange to Meet New Challenges,released by the Institute of Medicinethat made certain recommendationsregarding the organization of NIH,

H

Continued on next page


Scopes almost certainly appears in thephoto above; LaFollette says he is prob-ably the second seated fellow from theleft in the foreground, with thestraight hair and white shirt.

This and other photos were taken byWatson Davis, a photographer in thepay of the Science Service, a news andscience advocacy organization in itsinfancy at the time (but still extanttoday). Davis went on to lead the organ-ization until his death in the 1960s.

Darrow interrogated Bryant for twohours, and the next day John Scopes wasconvicted of teaching evolution and wasfined $100. The Butler Act making the

teaching of evolution illegal in Tennesseewas not repealed until 1967. Bryant, athree-time democratic presidential candi-date, dropped dead six days after the trial.

Interestingly enough, LaFollette saidthat Scopes was a physics and mathteacher, and never taught a single classon evolution. He agreed to be arrestedfor the crime because a group of busi-nessmen in Dayton thought it would begood for business if the town got a lotof publicity, so they arranged for thewhole show. The ACLU also got intothe act because they were concernedabout efforts to limit free speech, and soarranged for Darrow to defend Scopes.

The photo—in which Darrow isclosely eyeing Bryant who is wearing aconfident, faint smile—is one of thegreat and evocative photos in the his-tory of American science, and an eeriereminder of the continuing struggleswe face in science education todayover the issue of evolution, as shownin the next item.

UC System Sued forD iscr im inat ingaga inst H igh Schoo lsTeach ing Creat ion ism

The Associated Press reported in lateAugust that a group representing more

than 800 religious schools, theAssociation of ChristianSchools International, has fileda lawsuit accusing the Univer-sity of California system of dis-criminating against highschools that teach creationismand other conservative Christ-ian viewpoints. The suit claimsthat UC admissions officialshave refused to certify highschool science courses that usetextbooks challenging Dar-

win’s theory of evolution. A lawyer for the association told AP

that the UC policy violates the rightsof students and religious schools. A UCspokeswoman said the university has aright to set course requirements.

New Po l l Shows Pub l icWants Creat ion ismTaught a long w ithEvo lut ion

Two-thirds of the American publicwants creationism taught alongsideevolution in science classes, accordingto a new poll released on August 30 by

ince the theory of evolution,creationism, and intelligentdesign are now being dis-

cussed at the highest levels of govern-ment as education and public policyissues, ASBMB Today is going to start aregular update—of which this is thefirst—on events and news in this area.

New Photos Found of1925 Scopes “Monkey”Tr ia l

At a recent seminar at AAAS head-quarters in Washington, science histo-rian Marcelle LaFollette lectured on atreasure-trove of previously unknownphotos taken in Dayton, Ten-nessee, during the July 1925trial of physics teacher JohnScopes for teaching evolu-tion, in violation of a statelaw. The photo at right showsClarence Darrow (who repre-sented Scopes), thumbshooked in his galluses, cross-examining prosecutorWilliam Jennings Bryant. Thetrial had been moved outsidebecause of the intense heat.

Evolut ion WatchS

But ultimately, the bill will succeedor fail on the strength of its proposalsand whether the Congress and the sci-entific community can be convincedthat NIH will be better off under thenew structure. This is probably a toughsell. As one prominent ASBMB mem-ber told ASBMB Today, “Now that I’mold, I tend to be wary of overhaulingsomething like NIH under the guise ofimprovement. More important, I dis-trust putting too much discretionarypower in the hands of a Presidentialappointee.” Continued on page 12

Continued from previous page


N I H N E W S

he Department of Health andHuman Services (DHHS)released its revised “Supple-

mental Standards of Ethical Conductfor Employees of the Department ofHealth and Human Services” (mostlypertaining to NIH and Food and DrugAdministration employees) on August31, and most of ASBMB’s April 2005recommendations on needed changesin the draft regulations were accepted.

The regulations were issued in draftform in February. They called for verystringent restrictions on stock owner-ship among NIH employees, theirwives and family members; limitedoutside employment and charitablework they could perform; severelyrestricted their participation in aca-demic and scientific societies; andmade it almost impossible for a societysuch as ASBMB to present a scientificaward to an NIH employee.

These and other restrictions were pro-posed to address a problem that firstcame to public attention in December2003, when it was reported in the LosAngeles Times and other papers that hun-dreds of NIH employees had acceptedmoney, cash awards, and travel fundsfrom academic institutions, pharmaceu-tical companies and trade associationswithout reporting this on their financialdisclosure forms or in many cases seek-ing permission before doing so.

The draft regulations provoked wide-spread outrage among NIH employees,and over 1200 of them, as well as someof their wives and family members, sub-mitted comments on the draft regula-

T

DH HS Revises N I H Employee Confl ict of InterestRegs; Most AS BM B Recommendat ions Accepted

tions. The anger over the regulationseven prompted the reinvigoration of apreviously moribund staff organizationat NIH, the Assembly of Scientists, whichdeveloped an alternative proposal toaddress conflict of interest issues. WhileDHHS did not accept the Assembly’s spe-cific recommendations, the agency didnote that the Assembly had some influ-ence in DHHS’s revised regulatoryscheme; DHHS now differentiatesbetween NIH employees “as to rank,duties, and their level of responsibility formatters affecting public health and clini-cal research protocols involving humansubjects,” unlike in the draft regulationswhich treated all NIH employees alike.The most stringent restrictions now onlyaffect a few hundred senior NIH officials.

ASBMB commented on the draft reg-ulations in a letter to DHHS in April,noting six major objections and rec-ommending that the regulations bewithdrawn and redrafted. The ASBMBletter is available on the public affairspage on the Society website.

While the recommendations were notwithdrawn, they were substantiallyredrafted, and at least four of the ASBMBrecommendations were accepted.

First, professional and scientific soci-eties such as ASBMB are removed formthe list of entities known as “substan-tially affected organizations” (SAO)with which NIH employees are prohib-ited from engaging in outside activities.SAOs are mostly commercial entitiessuch as pharmaceutical companies.

This change allows NIH employees toparticipate in scientific societies such as

ASBMB as officers or committee or boardmembers, and also allows NIH employ-ees to teach, speak, write or edit for suchorganizations and their journals (withprior approval). NIH employees can alsoteach a course that requires multiple lec-tures; engage in clinical practice; andpresent a CME or CME-like lecture.

Regarding stock ownership restric-tions, senior employees (and theirspouses and minor children) may ownup to $15,000 in stock in a SAO, and anaggregate interest in SAO sector funds ofup to $50,000. Non-senior employeesmay hold any amount of interest in aSAO, with certain exceptions wherenecessary. Under the interim rule, sen-ior employees could not hold any inter-est in a SAO and non-senior employeeswere allowed up to $15,000 per SAO. Ingeneral, only those employees requiredto file a financial disclosure report, orwho serve as clinical investigators iden-tified on an NIH clinical study, arerequired to report the value of anyinterest in a SAO.

Regarding awards, restrictions put inplace by the draft regulations have beeneliminated. Now, with prior approval,employees (including senior level) canaccept gifts associated with bona fideawards for meritorious achievement.The only restriction is that if theemployee’s duties or those of any subor-dinates can affect the entity giving theaward, gifts valued in excess of $200may not be accepted. This changeappears to allow NIH employees inmost cases to accept ASBMB awards.

by Peter Farnham , CAE , ASBMB Pub l i c A f fa i rs O f ficer

Continued on page 10


cause more serious infection in other-wise healthy people.

The work also identified specific S.aureus genes that potentially control thebacterium’s escape from neutrophils.Among thousands of S. aureus genesanalyzed in the five different strainsused in the study, the scientists identi-fied a large group of genes whose role inhelping spread infection is unknown.RML’s Dr. Frank DeLeo, the investigatorwho directed the study, and colleaguesplan to determine if some of theunknown genes help promote disease.If they can learn which genes controlthe ability of S. aureus to evade anddestroy neutrophils, their work couldlead to new medical treatments.

“Each day physicians around theworld are stymied by the inability toeffectively treat patients suffering fromsevere S. aureus infections,” says NIAIDDirector Anthony S. Fauci, M.D.“There is a critical need to develop newtreatments against late-stage diseasecaused by antibiotic-resistant strains,and this promising work offers severalnew approaches.”

According to the Centers for DiseaseControl and Prevention, “recent reportsof ‘community-acquired’ MRSA infec-tions raise concern … If MRSA becomesthe most common form of Staphylococ-cus aureus in a community, it will maketreatment of common infections muchmore difficult.” The April 7, 2005, issueof The New England Journal of Medicinerefered in an editorial to “… an epi-demic of MRSA in the community.”

S. aureus strains acquired in health-caresettings can be challenging to resolvebecause of antibiotic resistance, whichlimits the choices for treatment. But thesituation can become more serious withthe newer community-acquired strains,says Dr. DeLeo. “We do not know whycases of community-acquired MRSAinfections are increasing, let alone howthey flourish,” he says. But scientists doknow the community strains can causemore severe forms of disease.

Mild S. aureus infections such asimpetigo, which typically forms smallblisters on the faces of children, or cel-lulitis, an inflammation of skin ormuscle tissue, can easily be treated andusually resolve in a matter of days. ButS. aureus disease also can be muchmore severe and difficult to treat,affecting vital organs and leading totoxins poisoning the blood and infec-tion overwhelming the heart. One ofthe most severe types of disease isnecrotizing pneumonia, where bacte-ria destroy lung tissue.

“The reason that some mild infec-tions become severe or fatal is not wellunderstood, but virulence is often asso-ciated with certain strains,” says Dr.Jovanka Voyich of RML, the study’slead author. To cause human disease,bacterial pathogens must avoid beingkilled by neutrophils. “These results,”says Dr. Voyich, “suggest that commu-nity-acquired MRSA causes disease inhealthy people in part because it hasenhanced ability to circumvent killingby neutrophils.”

study of how the immune sys-tem reacts to strains of antibi-otic-resistant Staphylococcus

aureus bacteria—emerging strains thatsicken otherwise healthy people, or so-called “community-acquired” infec-tions—has shown for the first time thatthese strains are more deadly and betterat evading human immune defensesthan more common S. aureus strainsthat originate in hospitals and otherhealth-care settings.

In a paper released September 7online in The Journal of Immunology,scientists from the National Institute ofAllergy and Infectious Diseases (NIAID)describe how community-acquired S.aureus strains that survive treatmentwith the methicillin family of antibi-otics can evade immune defenses.Infections from community-acquiredmethicillin-resistant S. aureus, orMRSA, are difficult to treat and areincreasing nationally at an alarmingrate, say experts.

Scientists at NIAID’s Rocky Moun-tain Laboratories (RML) in Hamilton,Montana, and colleagues examinedthe ability of MRSA strains to cause dis-ease in mice and avoid destruction byhuman white blood cells called neu-trophils. Neutrophils, which typicallyingest and then kill harmful bacteria,make up about 60% of all white bloodcells and are the first line of defenseagainst bacteria. Scientists know thatcommunity-acquired strains differfrom hospital strains, but they don’tknow why the community strains

Emerg ing Staph Strains IncreasinglyDeadly and Decept ive A


received the ASBMB-Avanti Award inLipids at the ASBMB Annual Meeting in2000. He explains the goals of LIPIDMAPS as, “To characterize known lipidsand identify new ones, quantitate thetemporal and spatial changes in lipidsthat occur with cellular metabolism,and develop bioinformatics approachesthat establish dynamic lipid networks.In order to coordinate their efforts withthose of other groups, such as the LipidBank in Japan, the EuropeanLipidomics Initiative, and the Interna-tional Conference on the Biochemistryof Lipids based in Europe and to facili-tate international collaboration, LIPIDMAPS initiated the development of acomprehensive classification system forlipids suitable for data–basing andbioinformatics manipulations.”

L ip id C lass i ficat ionand Databases

“The classification system wasdesigned to be a broad-based schemecovering eukaryotic and prokaryoticsources, to include new classes of lipidswhich have been discovered in recentyears, to be extensible to accommodatefuture novel classes and to be compati-ble with modern-day informaticsrequirements,” explains Dr. Eoin Fahy,of the San Diego Supercomputer Centerat UCSD, who serves as LIPID MAPS’Bioinformatics Project Coordinator.

LIPID MAPS’ classification divideslipids into eight primary categories:fatty acyls, glycerolipids, glycerophos-

pholipids, sphingolipids, sterol lipids,prenol lipids, saccharolipids, andpolyketides. These categories are basedon the functional backbone of thelipid molecule from a chemical stand-point and is lipocentric. The categoriesare further subdivided into classes andsubclasses to handle the existing andemerging arrays of lipid structures.

In conjunction with their proposedlipid classification scheme, the grouphas also proposed a nomenclature sys-tem. “The nomenclature rules adoptedby LIPID MAPS follow existing IUPAC-IUBMB rules closely and should not beviewed as a competing format,”emphasizes Fahy. “The main differ-ences involve clarification of the use ofcore structures to simplify systematicnaming of some of the more complexlipids, provision of systematic namesfor recently discovered lipid classes,and clarification of abbreviations andshorthand names for lipids.”

A key part of the classification systemis a 12-digit identifier for each uniquelipid molecule, called a LIPID ID. Theidentifier is based on the classificationscheme and will be used mainly indatabases, such as the LIPID MAPSdatabase. The LIPID ID format providesa systematic means of assigning uniqueIDs to lipid molecules and allows forthe addition of large numbers of newcategories, classes and subclasses in thefuture. The first two characters (1-2) ofthe ID contain the database identifier(e.g. LM for LIPID MAPS). Characters 3-4 correspond to the lipid category, 5-6to the class within that category, and 7-8 to the subclass. The last four charac-ters of the ID comprise a uniqueidentifier within a particular subclassand are randomly assigned.

The new classification system hasalready been implemented, and scien-

hile genes and proteins havelong held starring roles in bio-medical research, lipids—fats

and oils—often have a more directeffect on human health.

University of California, San Diego(UCSD) investigator Edward Dennis,Professor of Chemistry and Biochem-istry and of Pharmacology in UCSD’sDivision of Physical Sciences andSchool of Medicine, is currently leadingan ambitious national effort to producea detailed understanding of the struc-ture and function of lipids—cellular fatsand oils—implicated in a wide range ofdiseases, including heart disease, stroke,cancer, diabetes, and Alzheimer’s.

In response to the growing number oflipids expected to be discoveredthrough lipidomics and in anticipationof the massive amounts of data that willbe generated by the lipid community,an international group of scientists hasdeveloped a comprehensive classifica-tion, nomenclature, and chemical rep-resentation system for lipids. The detailsof the system appeared in the May 2005issue of the Journal of Lipid Research,an ASBMB journal.

The new system is part of an effortby the Lipid Metabolites and PathwaysStrategy (LIPID MAPS) consortium toproduce a detailed understanding ofthe structure and function of all thelipids within a cell. The consortium is alarge collaborative effort led by UCSDand funded by a $35 million “GlueGrant” from the National Institute ofGeneral Medical Sciences. The five-year grant involves more than 30researchers at 8 universities, medicalresearch institutes, and companiesacross the United States.

Serving as Director of LIPID MAPS isDr. Dennis whose expertise in lipidresearch was recognized when he

WIn Ed Dennis’ Lab Lipids

Edward Dennis consid-ers his tenure as Chairof the Keystone Sym-

posia Board one of themost fulfilling experi-

ences of his career


Examples of the classificationscheme and interactive access to it canbe viewed on the LIPID MAPS websiteat http://www.lipidmaps.org.

L ip id MapsKnowledge gained through the Lipid

Maps Consortium will help medicalresearchers develop better diagnosticdevices and more effective ways totreat some of the common diseasesthat result from problems in the waycells use lipids. Imbalances in lipidscause or play a role in diseases thataffect millions of people worldwide.High cholesterol has been implicatedin cardiovascular disease, which killedabout 950,000 Americans in 2002,

according to the American Heart Asso-ciation. Lipids produced by immunesystem cells are involved in inflamma-tory diseases such as rheumatoidarthritis, sepsis, asthma and inflamma-tory bowel disease, and also play a rolein Alzheimer’s disease and cancer.Essential to life, lipids come in a widevariety and have many functions inthe cell. They can be stored as anenergy reserve for the cell. They makeup cell membranes and are involved incommunication within and betweencells. “Lipids are the most importantbiomolecules because they are the ulti-mate controllers and regulators of ourbodily processes,” says Dennis. TheConsortium is divided into six focus

tists from Europe, Asia, and the U.S.are looking for it to gain widespreadacceptance. “Inevitably, there will besome resistance, possibly from otherswho have created alternative schemesor who are long-time proponents ofother formats,” acknowledges Dr. Fahy.“However, the Journal of LipidResearch manuscript outlining thisclassification scheme contains an inter-national panel of authors (several ofwhom are not involved with the LIPIDMAPS project) and has also beenreviewed by several other experts inthe lipid research field, so it representsa well-balanced consensus view ofwhat a modern-day lipid classificationscheme should be.”

Take the Spotl ight


world. Over 12,000 biomedical scien-tists attend these meetings each yearincluding about a third grad studentsor postdocs, many on scholarships pro-vided by Keystone. This month, forexample, it is hosting symposia on Tis-sue-Selective Nuclear Receptors inBreckenridge, Colorado, and in Octo-ber will run a symposia in Singapore onStem Cells, Senescence, and Cancer.Over 400 bioscientists are expected toattend the Singapore meeting.

Organized in 1972 as the UCLASymposia on Molecular and CellularBiology, the organization later becamea subsidiary of The Keystone Centerand was renamed the Keystone Sym-posia. In 1997, the Keystone Symposiabecame an independent 501(c)(3) non-profit organization based in Silver-thorne, Colorado. Dennis served asPresident and Chair of Keystone’sBoard of Directors for the first eightyears, a period when the Keystoneorganization grew dramatically andthe number of symposia increased sub-stantially. Currently a member of theKeystone Board, he considers his timeas founding Chair one of the most ful-filling experiences of his career.

The Denn is Group ’sFocus

The Dennis Group has studied thestructure and function of phospholi-pases for the past 35 years, and hasextensively characterized the cobravenom phospholipase A2 and fromthese studies developed a model forthe action of soluble enzymes at phos-pholipid surfaces. These studies werethen extended to numerous otherenzymes that act on lipid substrates atmembrane and micellar interfaces. Thelab also explored the role that theseenzymes play in various cell functionsin macrophages and other cells, and incellular signal transduction in general.

“Our laboratory,” explains Dr. Den-nis, “is focused on understanding theregulation of lipid second messengersand signal transduction processes andespecially the role of various phospholi-pases in their generation. Special atten-tion is paid to the cytosolic, secreted,and membrane-bound phospholipaseA2s (PLA2) responsible for the controlof prostaglandin and leukotrienebiosynthesis in macrophage cells. Theseare produced from arachidonic acidreleased by PLA2 upon cell stimulation.Our goal is to characterize and eluci-date the regulatory mechanisms of vari-ous phospholipase A2s both in vitroand in the intact cell.”

areas. The lipidomics focus area willinvestigate the six major groupings oflipids that occur in mammalian cells.Other scientific focus areas will coverinformatics, cell biology, lipid detec-tion and quantitation, and lipid syn-thesis and characterization. More than40 faculty-level researchers at 15 uni-versities and three corporations areinvolved in the actual research or asparticipating investigators advising onthe actual experiments.

The KeystoneSympos ium

Dr. Dennis is also well known for hisrole in leading the Keystone Sympo-sium, a Silverthorne, Colorado basedorganization that serves as a catalyst forthe advancement of biomedical andlife sciences by connecting scientistswithin and across disciplines at confer-ences and workshops held at venuesthat create an environment conduciveto information exchange, generation ofnew ideas, and acceleration of applica-tions that benefit society. Keystonesponsors over 50 scientific symposia ayear, mostly at Western ski resorts, butalso now at locations throughout the

An avid skier, Dr. Dennis is seen here on one ofthe slopes near Keystone Symposia’s headquar-

ters in Colorado.

N I H News Cont inued …

Senior NIH scientist Edward Korn,with the National Heart, Lung andBlood Institute (and an active memberof the Assembly of Scientists), tellsASBMB Today that “The revisions madein the final rule fully satisfy most of ourconcerns, in particular those having todo with the restrictions the interim ruleimposed on interactions of intramuralscientists with academia and profes-sional societies, and the stock divestitureissue. The issue of consulting with

industry remains, but this is a difficultproblem and not just for NIH. It is myhope and expectation that this positiveresponse by NIH and DHHS will removeany retention or recruitment problemsthat the interim rule may have created.”

A summary of the new regulations,as well as a link to the final regulationsthemselves, is available on the NIHhome page (www.nih.gov). Click onthe phrase, “conflict of interest infor-mation” in the lower left portion ofthe home page.

Continued from page 6

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the heightened photosynthetic activityalso means an increase in singlet oxy-gen. By modifying plants to enhancethe protective pathway, “we could beable to get larger crop yield per photonof light,” he says.

And by making cells more resistantto singlet oxygen, scientists may bebetter able to design bioenergy systemsthat use sunlight as an alternative totraditional fossil fuels. “By understand-ing how biology solves this problem,we can fine-tune the design of thesesystems to minimize the harmfuleffects of singlet oxygen and enhanceenergy production.”

Reactive oxygen also plays an impor-tant role in human, animal and planthealth, because it is often used as ahost defense to inhibit the growth ofunwanted microbial pathogens. In

fact, it appears that even non-photo-synthetic bacteria, including humanand animal pathogens like Vibrio andPseudomonads have systems to senseand protect themselves from singletoxygen, says Donohue. Other reactiveoxygen species—often called “free radi-cals”—are thought to be at the root ofmany debilitating diseases.

“There have been considerableadvances in our understanding of howcells protect themselves from severalreactive oxygen species,” says Dono-hue. “However, nothing has previouslybeen known about how cells alter geneexpression to respond to singlet oxy-gen. We may now be able to designpharmaceuticals that target thisresponse, and ultimately may help usmitigate disease.”

* ASBMB member

newly discovered pathway bywhich cells protect them-selves from a toxic byproduct

of photosynthesis may hold importantimplications for bioenergy sources,human and plant disease, and agricul-tural yields, a team of University ofWisconsin-Madison bacteriologistsannounced June 6 in the Proceedings ofthe National Academy of Sciences.

Plants turn energy from sunlightinto bioenergy through a chemicalprocess called photosynthesis, whichalso produces oxygen in its breathableform. However, photosynthesis canalso generate an alternate form of sin-glet oxygen, which is a highly reactiveand toxic substance that destroys bio-logical molecules.

“We’ve discovered a pathway thatcells use to turn on certain genes andrespond to singlet oxygen,” says Timo-thy Donohue,* Professor of Bacteriol-ogy in the university’s College ofAgricultural and Life Sciences and leadresearcher on the paper.

“This finding should make it possi-ble to modify plants and other photo-synthetic cells to avoid the toxic effectsof singlet oxygen, which could impactagriculture and the treatment ofhuman and plant disease, and aid theeffort to create alternative bioenergysources,” Donohue says.

Donohue and his group studied aphotosynthetic microbe and identifiedthe cellular pathways it used to sensethe presence of singlet oxygen anddefend itself from this toxic substance.He notes that the response mechanismis likely highly conserved across speciesfrom microbes to plants and humans -and therefore very applicable to otherfields of study.

For example, too much sunlight canactually be harmful to plants, because

A

Scient ists Discover How Plants DisarmToxic Effects of Excessive Sunlight

the Pew Forum on religion and PublicLife and the Pew Research Center forthe People and the Press.

The poll found that 42 percent ofrespondents believe that “living thingshave existed in their present formsince the beginning of time.” While 48percent believed that humans hadevolved, 18 percent of those said thatevolution was “guided by a supremebeing” and 26 percent said that evolu-tion occurred through natural selec-tion. In all, 64 percent said they wereopen to the idea of teaching creation-ism in addition to evolution.

The poll showed 41 percent ofrespondents wanted parents to havethe primary say over how evolution istaught, compared with 28 percent whosaid teachers and scientists shoulddecide and 21 percent who said school

boards should. Asked whether theybelieved creationism should be taughtinstead of evolution, 38 percent were infavor, and 49 percent were opposed.

Robert Park, a University of Mary-land physicist and long-time sciencepolicy commentator, notes that despitethis latter “scary” statistic, “the tinyglimmer of hope for civilization wasthe number of inconsistencies in theresponses, suggesting confusion overthe meaning of the terms. There isroom for education.”

FASEB's Office of Public Affairs has aweb page featuring tools for teachingevolution to K-12, statements by scien-tific societies regarding evolution, andother sources of information. The pageis at www.faseb.org/opa/ppp/evolu-tion.html.

The Pew report can be read athttp://pewforum.org.

Evolut ion Watch cont inued …Continued from page 5

Scient ists Discover How Plants DisarmToxic Effects of Excessive Sunlight


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A N N U A L R E V I E W SIntelligent Synthesis of the Scientific Literature

w w w . a n n u a l r e v i e w s . o r g

1. When and by who was the ß-oxidation of fatty acidsdeduced?

2. Who postulated a respiratory enzyme for the activation ofoxygen and showed the requirement of iron in respiration,and in what year when was this done?

3. Who first crystallized an enzyme, urease, and proved it be aprotein and when was this done?

4. Who discovered the urea cycle and when?5. When and by whom was threonine discovered?6. When and by whom was the central role of ATP in the

energy transfer cycle postulated?7. Who discovered that acetate is the precursor of cholesterol,

and when was this done?8. How many ASBMB members were Nobelists in 1946 and

what were their names.9. Who discovered the base equivalences in DNA, and when

was this done?10. How many ASBMB members were Nobelists in 1972, and

who were they?

If you get all 10 of the answers to these questions right, youare entitled to be called an ASBMB Centennial Expert and willbe eligible for all the perquisites thereof.NOTE: Information for this test was supplied by William Lennarz, SUNY at

Stony Brook, New York.

ANSWERS :

So You Think You KnowBiochemistry History?Try the ASBMBCentenn ia l Qu izLet ’s see how we l l you doanswer ing these quest ions aboutevents dur ing ASBMB ’s fi rsthundred years .

1. Knoop deduced the ß-oxidation of fatty acids in 19052. Warburg showed the requirement of iron in respiration in 1912.3. Sumner first crystallized urease, in 1926.4. Krebs and Henseleit discovered the urea cycle in 1933.5. Rose discovered threonine, the last essential amino acid to be recognized, in

1935.6. Lipmann postulated the central role of ATP in the energy transfer cycle in

1939.7. In 1942, Bloch and Rittenberg discovered that acetate is the precursor of cho-

lesterol.8. Three ASBMB members were Nobelists in 1946; they were John H. Northrop,

Wendell M. Stanley, and James B. Summer.9. Chargaff discovered the base equivalences in DNA in 1950.10. There were five ASBMB Laureates in 1972: Gerald M. Edelman, Stanford

Moore, Rodney Porter, William H. Stein, and Christian B. Anfinsen.

A S B M B C e n t e n n i a l C e l e b r a t i o n : C h e m i s t r y o f L i f e


type of people who are good scientists,”said Cech in a recent address. “It wouldbe a pretty dull job if that were thecase. The truth is that people with awide variety of training, personalitytraits, skills in very different areas cancontribute a lot to scientific discoveries.

”Certainly there are certain traitsthat scientists tend to have in com-mon. But, it isn’t always true that thepeople who are the brilliant highschool students, who get the highestgrades on the exam, are the ones whodo well as practicing, experimental sci-entists. There are a lot of skills in doingexperimental science that can’t betested on standardized exams.Although good mathematical ability,good quantitative ability, good analyti-cal thinking ability are part of being agood scientist, there’s a very hard-to-quantitate element. And it should beencouraging to those students who arethe B students in high school and theB students in college that very oftenthey are the ones who end up doingthe really great work in research.”

”My father, who loved physics asmuch as medicine,” recalled Cech,“interjected a scientific approach andpoint of view into most every familydiscussion. I discovered science formyself in fourth grade, collecting rocksand minerals and worrying about howthey were formed. By the time I was injunior high school, I would knock onGeology professors’ doors at the Uni-versity of Iowa, asking to see models ofcrystal structures and to discuss mete-orites and fossils.”Research Areas

Thomas Cech’s main research area isthat of the process of transcription inthe nucleus of cells. He studies how

the genetic code ofDNA is transcribedinto RNA. In the1970s, he had beenstudying the splic-ing of RNA in theunicellular organ-ism Tetrahymenathermophiliawhen he discovered that anunprocessed RNA molecule couldsplice itself. In 1982, Cech became thefirst to show that RNA molecules arenot restricted to being passive carriersof genetic information—they can havecatalytic functions and participate incellular reactions. RNA-processing reac-tions and protein synthesis on ribo-somes in particular are catalyzed byRNA. RNA enzymes are known asribozymes and have provided a newtool for gene technology. They alsohave the potential to provide newtherapeutic agents - for example, theyhave the ability to destroy and cleaveinvading, viral RNAs.

Dr. Cech has a second, very differentarea of research, that of the structureand function of telomeres, the naturalends of linear chromosomes. He andhis research group focus on the assem-bly, structure and function of telom-erase, the enzyme that copies thetelomeric sequences. The active siteprotein subunits of telomerase com-prise a new class of reverse transcrip-tases, enzymes previously thought tobe restricted to viruses and transpos-able elements. Telomerase, an impor-tant enzyme in biomedical terms, isactivated in 90% of human cancers.Therefore, a drug that would inhibit itsactivity is much sought after as a can-cer chemotherapeutic.

he ASBMB Awards Commit-tee has selected Thomas R.Cech to receive the inaugural

ASBMB Award for Exemplary Contri-butions to Education. Cech, Presidentof Howard Hughes Medical Instituteand Professor, Department of Chem-istry and Biochemistry, University ofColorado, will receive the award at the2006 ASBMB annual meeting, whichalso marks the centennial of ASBMBand its foundation publication, theJournal of Biological Chemistry.

The ASBMB Award for ExemplaryContributions to Education, a newaward this year, will be given annuallyto a scientist who encourages effectiveteaching and learning of biochemistryand molecular biology through the sci-entist’s own teaching, leadership ineducation, writing, educationalresearch, mentoring or public enlight-enment. It includes a cash prize as wellas paid travel and expenses to present aplenary symposium lecture at the 2006Society meeting. That lecture is cur-rently scheduled for Sunday, April 2.

Does success in high school lead tosuccess in science? Not necessarily saysCech, who won the Nobel Prize for hisdiscoveries about the catalytic proper-ties of RNA. “It isn’t always true thatthe people who are the brilliant highschool students, who get the highestgrades on the exam, are the ones whodo well as practicing, experimental sci-entists. There are a lot of skills in doingexperimental science that can’t betested on standardized exams.” B stu-dents, he notes, often “are the oneswho end up doing the really greatwork in research.”

“I think the general public perceivesthat there’s a lot of homogeneity in the

T

AS BM B to Honor Thomas Cech forExemplary Contribut ions to Educat ion

Dr. Thomas R. Cech

MOLECULAR STRUCTURE Macromolecular Structure and DynamicsAndrej Sali, UCSF

Proteomics and Bioinformatics Michael Snyder, Yale UniversityDavid S. Eisenberg, UCLA

Chemical Genetics and Drug DiscoveryChaitan Khosla, Stanford University Kevan Shokat, UCSF

Glycobiology and Extracellular MatrixCarlos B. Hirschberg, Boston University Goldman School of Dental Medicine

GENOME DYNAMICSGenome Dynamics: Replication, Repair, and Recombination Laurie S. Kaguni, Michigan State University

Chromatin: Structure, Expression, and RegulationSharon R. Dent, University of Texas M. D. Anderson Cancer Center

RNA: Structure, Metabolism, and Regulation Alan D. Frankel, UCSF

Protein Synthesis, Folding and TurnoverWilliam Merrick, Case Western Reserve University

CELL SIGNALINGMetabolic RegulationRichard W. Hanson, Case Western Reserve UniversityDaryl K. Granner, Vanderbilt University

Signaling in Growth and DevelopmentMichael B. Yaffe, MIT

Signaling in Aging and Disease Natalie G. Ahn, University of Colorado at Boulder

Award LecturesHerbert Tabor/Journal of Biological Chemistry LectureshipASBMB-Amgen AwardASBMB Award for Exemplary Contributions toEducationASBMB-Merck AwardAvanti Award in LipidsFASEB Excellence in Science Award Herbert A. Sober LectureshipHoward K. Schachman Public Service AwardSchering-Plough Research Institute AwardWilliam C. Rose Award

MEMBRANE BIOGENESISBiochemistry and Molecular Biology of Lipids George M. Carman, Rutgers UniversityChristian R.H. Raetz, Duke University

Structure, Function, and Biogenesis of Cell MembranesWilliam Dowhan, University of Texas-Houston Medical School

MINORITY AFFAIRS COMMITTEE SPONSOREDSYMPOSIAJuliette Bell, Fayetteville State University

Issues in Breast Cancer Among Minority Populations Chair: K.V. Venkatachalam, Nova Southeastern University

Minorities and the HIV/AIDS Epidemic Chair: Juliette Bell, Fayetteville State University

EPD/MAC Symposium – Undergraduate Student/Faculty Science Chairs: Joseph Provost, Minnesota State University-Moorhead,Mark A. Wallert, Minnesota State University-Moorhead andPhillip A. Ortiz, Empire State College

EPD/MAC Symposium – Outreach and Public Education Chair: Neena Grover, Colorado College

EDUCATION and PROFESSIONAL DEVELOPMENT:Focus on the Future, Shape the Debate J. Ellis Bell, University of Richmond

Undergraduate Poster Session and Plenary Lecture: My Life in Science Edmond H. Fischer, University of Washington School ofMedicine and Edwin G. Krebs, University of WashingtonSchool of Medicine

Current Themes in Molecular Evolution Chair: Michael M. Cox, University of Wisconsin – Madison

Plenary Lecture: Integrity and Independence of Scientific Thought Elizabeth Blackburn, University of California, San Francisco

Matching Expectations: Employers and Education in the MolecularLife Sciences Chair: Joy A. McMillan, Madison Area Technical College

The Classroom of the Future J. Ellis Bell, University of Richmond

Centennial Special EventsCentennial Opening Celebration

An Evening with the San Francisco Symphony

Birthday Bash, A Taste of San Francisco

ASBMB 5k Fun Run

www.asbmb.org/meetings

April 1-5, 2006 • San Francisco, CA 2006 Program Co-Chairs: George M. Carman, Rutgers University and Laurie S. Kaguni, Michigan State University

Centennial Celebration

Centennial Special Events

Award Lectures

ASBMB 2006Centennial CelebrationASBMB 2006

Thematic MeetingsThematic Meetings



Regu lat ion of L ip idMetabo l ism

The phospholipid precursor inosi-tol plays a major role in the regula-tion of phospholipid metabolism inyeast. Dr. Susan Henry (Cornell Uni-versity) will discuss a comprehensivemicroarray study of the kinetics oftranscriptional changes in responseto addition of inositol to the growthmedia of logarithmically-growingwild type yeast cells. The genome-wide changes in transcription will bepresented in conjunction with analy-sis of simultaneous changes in lipidmetabolism including phospholipids,neutral lipids, and sphingolipids.Given the essential roles that phos-pholipids play in the structure andfunction of cellular membranes, cellshave the ability to cope with a varietyof stress conditions by regulatingexpression of key phospholipidbiosynthetic enzymes.

Dr. George Carman (Rutgers Univer-sity) will discuss transcriptional mecha-nisms in yeast that control membranephospholipid composition in responseto the stress of zinc deprivation. Sphin-gosine-1-phosphate is a bioactivesphingolipid that regulates prolifera-tion, differentiation, migration, andapoptosis) in higher eukaryotic organ-isms. Intracellular levels of sphingo-sine-1-phosphate are controlled in partby its irreversible degradation by thesphingosine-1-phosphate lyase enzymeencoded by the SPL gene. Recent stud-ies have suggested that SPL expressionaffects animal development and cellfate decisions.

Dr. Julie Saba(Children’s HospitalOakland ResearchInstitute) will dis-cuss studies explor-ing various aspectsof sphingosine-1-phosphate lyaseregulation, includ-ing conserved mechanisms of transcrip-tional regulation of the SPL gene, aswell as pharmacological modulation ofthe enzyme.

Pharmaco log ica lTargets in L ip idMetabo l ism

Lipids such as essential fatty acids,sphingolipids, and cholesterol playimportant roles in cell signaling aslipid mediators and in membranefunctions as components of cellmembranes. Fatty acids are essentialto life in all organisms. Interestingly,there are significant biochemical dif-ferences in the properties of the fattyacid biosynthetic machinery amongspecies. Dr. Charles Rock (St. Jude’sChildrens Research Hospital) will dis-cuss how these differences are beingexploited in efforts to develop anti-microbial drugs. Research in the labo-ratory of Dr. Sarah Spiegel (VirginiaCommonwealth University School ofMedicine) focuses on sphingosine-1-phosphate and the roles this lipidplays in cell growth, apoptosis, tumorangiogenesis, and immune responses.Two isoenzymes of the sphingosinekinase, the enzyme responsible forsynthesizing sphingosine-1-phos-

ur understanding of lipidbiosynthesis and its regula-tion has increased greatly

over the past few years because ofadvances in biochemical, structuraland molecular genetic approaches,combined with genomic and pro-teomic studies of both prokaryotic andeukaryotic organisms.

The Biochemistry and Molecular Biologyof Lipids theme will primarily focus onthe roles that lipids play in membranebiogenesis and function. It will coverrecent mechanistic studies of lipidbiosynthetic enzymes, as well as thestructural biology of lipid flippases andpumps. Its complementary theme,Structure, Function and Assembly of Mem-branes (summarized in the August issueof ASBMB Today), focuses mainly onthe protein component of membranesand integrates information on howmembrane proteins interact with lipids.

The symposia of each theme will bescheduled on alternating mornings andafternoons to allow flexibility of atten-dance. In addition, social gatherings areplanned following the afternoon sym-posia to foster interactions among theparticipants of both themes.

In addition to the invited speakers,postdoctoral fellows and graduate stu-dents will be chosen from the submit-ted abstracts to give short talks. We arepleased to announce that ASBMB-Jour-nal of Lipid Research, Avanti PolarLipids, Elsevier-Biochimica et BiophysicaActa, and Merck will sponsor cashawards, not only for outstanding shorttalks but also for excellent poster pre-sentations by young investigators.

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Biochemistry and MolecularOrgan izers : George M . Carman , Rutgers Un ivers i ty,

Chr ist ian R .H . Raetz , Duke Un ivers i ty Med ica l Center

Dr. George M. Carman

S a n F r a n c i s c o , C a l i f o r n i a , A p r i l 1 - 5 , 2 0 0 6


Dr. JoAnne Stubbe (MIT) will dis-cuss the mechanisms by which poly-ß-hydroxybutyrate granules areformed. One model is that the gran-ules bud from the inner membraneof Gram-negative bacteria into thecytoplasm. This unique system,which has applications in biotech-nology, shares some common fea-tures with lipoprotein formation inthe endoplasmic reticulum of animalcells, and may address fundamentalissues in the regulation of lipidmetabolism.

Finally, Dr. Geoffrey Chang (ScrippsInstitute) will discuss his recent workon the structure and mechanism ofMsbA, an essential inner membraneABC transporter, closely related tomammalian MDR proteins. The E. coliMsbA protein is the flippase for someof the phospholipids generated on theinner surface of the inner membrane.MsbA is essential for growth and isabsolutely required for the export ofboth phospholipids and lipopolysac-charide to the outer membrane. Thissymposium is intended to bringtogether investigators working at theforefront of membrane biochemistry,enzymology, structural biology, lipidmetabolism, drug discovery, andmicrobiology.

L ip idomics ofMetabo l ic S igna l ing

The systems biology exploration ofgenomics and proteomics of recentyears has set the stage for ametabolomics revolution to identifyand quantify the individual metabo-

lites of cells. Lipids compose themajor cellular metabolites engaged inbiomolecular signaling, the genera-tion of lipid second messengers andmediators as well as the major mole-cules of energy metabolism and mem-brane remodeling. This symposiumwill focus on several aspects oflipidomics highlighting specificallythe eicosanoids, phospholipids, andsphingolipids as some of the impor-tant lipids comprising the lipidome.

The uses of new LC/MS techniquesto separate, detect, and quantify indi-vidual molecular species of lipidswith sophisticated extraction tech-niques and quantitative internal stan-dards and changes in their levels withcellular perturbations will be empha-sized. Dr. Edward Dennis (Universityof California, San Diego) will describethe LIPID MAPS approach tolipidomics and his detailed analysisof the time dependent changes in thelevels of a large number ofprostaglandins upon treatment withLPS and a homogeneous form of LPScalled Kdo2-Lipid A developed by theLIPID MAPS Consortium.

Dr. Alex Brown (Vanderbilt Univer-sity School of Medicine) will describehis array analysis of over 500 molecu-lar species of phospholipids and theirchanges upon LPS and Kdo2-Lipid Atreatment of RAW macrophage cells.Dr. Al Merrill (Georgia Institute ofTechnology) will discuss the numer-ous individual molecular species ofsphingolipids and the creation of“Sphingomaps” to describe theirmetabolic interactions.

phate, have beenidentified.

Dr. Spiegel willdiscuss how thesphingosine kinaseisoenzymes canboth phosphory-late sphingosineyet have either

opposite, overlapping, or complemen-tary functions in cells. The brain con-tains more cholesterol than any othertissue in the body, and it uses a uniquebiochemical pathway to metabolismthis essential lipid. Catabolism isaccomplished by the enzyme choles-terol 24-hydroxylase, a microsomalcytochrome P450.

Dr. David Russell (University ofTexas Southwestern Medical Center)will discuss the roles of cholesterol 24-hydroxylase and cholesterol turn overin the central nervous system.

Structura l B io logyand Mechan isms ofMembrane L ip idAssembly

Recent advances in the field of mem-brane biogenesis, with a focus onmodel systems, will be addressed inthis symposium. Dr. Christian Raetz(Duke University) will present anoverview of the enzymatic assembly ofouter membrane lipids in Escherichiacoli, including recent studies of slow,tight-binding inhibitors. Compoundsblocking the formation of outer mem-brane lipids are novel antibiotics, withpotency in some instances rivalingthat of ciprofloxacin.

Biology of Lipids

Dr. Christian Raetz



porally specific fashion during mouse,worm and Drosophila development.At least one Drosophila isoform, pgant35A, is required for normal develop-ment. Recent work with mouse modelspoint to multiple fuctional rolesrelated to systems as diverse as bonedevelopment and innate and adaptiveimmunity. Mutations in the humangene GALNT3 have recently beenshown to result in familial tumoral cal-cinosis.

Jacques Baenziger (Washington Uni-versity) will discuss the role of glyco-protein hormones and the way inwhich unique sulfated sugars con-tribute to functions of the glycopro-teins e.g. receptor activation and thedevelopment of neuronal connections.Glycoprotein hormones such as leu-tinizing hormone and thyroid stimu-lating hormone in the pituitary as wellas the matrix protein tenascin-R andthe LDL-receptor homolog SorLA/LR11in the brain, each have carbohydratesthat are selectively modified with ter-minal ß1,4-linked GalNAc-4-SO4residues which contribute to the theirbiological function.

G lycans in Pathogen icProtozoa : the SweetTouch of Death

The cell surface architectures of pro-tozoan parasites are fined-tuned totheir modes of infection and survivalin their mammalian hosts and insectvectors. Furthermore, parasite surfacemolecules can subvert the hostimmune response. In many cases, par-asite cell surfaces are dominated byGPI-anchored glycoproteins and/orGPI-related glycophospholipids.Depending on the species, cell surface

and secreted glycoproteins may alsocontain conventional or unusual N-linked glycans and/or novel O-linkedglycans and/or novel phosphate-linkedglycans. In addition, intracellular stor-age polysaccharides in some parasitesare proving to be unusual in theirstructure and assembly.

Michael Ferguson’s (University ofDundee, U.K.) presentation will be onthe structure and assembly of the cellsurface of trypanosomes. The struc-tural variation in parasite glycoconju-gates, and their central roles in parasitesurvival and infectivity presents majorchallenges for the future. Bioinformat-ics is playing a major role in miningparasite DNA databases for putativeglycosylation genes and pathways andis allowing functional glycomics stud-ies via gene knockouts and RNAiexperiments.

John Samuelson’s (Boston Univer-sity) presentation will address whatprotists tell us about the evolution ofN-linked glycosylation. Several of theparasite glyconconjugate biosyntheticpathways have been validated as drugtargets. Structural biology and chemi-cal biology approaches to anti-parasitedrug development are ongoing. Mal-colm McConville’s (University of Mel-bourne, Australia) presentation willaddress the glycobiology of Leishma-nia - glycan biosynthesis and virulencein the mammalian host.

Prote in-G lycanFunct iona lInteract ions

The existence of a vast array of gly-can structures provides the cell and theorganism with opportunities for imple-menting important biological func-

arbohydrates covalentlylinked to proteins and lipidsplay pivotal roles in the

development of higher and lowereukaryotes, cell-cell and cell-extracellu-lar matrices interactions, immunobiol-ogy, protein folding quality controland hormonal functions. The aim ofthis symposium is two fold (1) to givethe general scientist an overview ofsome of the principal areas in biologywhere glycobiology and extracellularmatrix components are essential tounderstanding biological functionsand (2) to allow the specialist to hearabout the latest developments of theseareas. Each symposium will have threeadditional talks selected from submit-ted abstracts.

The Ro le of G lycansin Deve lopment andD isease

Dr. Hirschberg will discuss the role ofthe nucleotide sugar transporter/antiporter cycle in eukaryotic develop-ment and disease. This cycle, whichoccurs in all eukaryotes studied to date,has as its function the transport ofnucleotide sugars into the lumen of theGolgi apparatus where they serve assubstrates for glycosylation of proteinsand lipids. Mutations in the cycle maylead to abnormal phenotypes e.g. fail-ures in tissue development and to dis-eases such as Leukocyte adhesiondeficiency syndrome II.

Lawrence Tabak (NIDCR, NIH) willdiscuss the roles of the many polypep-tide: N-acetylgalactosaminyltrans-ferases in development and disease ofthe craniofacial complex. Conservedthroughout evolution, family mem-bers are expressed in spatially and tem-

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Glycobiology and Extracel lular MatrixOrgan izer : Car los B . H i rschberg , Boston Un ivers i ty Go ldman Schoo l of Denta l Med ic ine



tions. This session will focus on how theinformation encoded within glycans isrecognized and deciphered by carbohy-drate-binding proteins - “lectins”, andwill highlight examples of protein-glycaninteractions in the secretory pathway.Asn-linked glycans act as maturation andquality control tags in the endoplasmicreticulum (ER). There are several playersin the quality control of glycoprotein folding. These includethe folding sensor that adds a glucose unit to species not dis-playing their native structure (UDPGlc:glycoprotein gluco-syltransferase, GT), the enzyme that removes those residues(glucosidase II), as well as the lectins that recognize themonoglucosylated glycans (calreticulin/calnexin).

Armando Parodi (Fundacion Instituto Leloir, Buenos Aires,Argentina) will describe his work concerning the structure-function relationships in this group of enzymes. DanielHebert (University of Massachusetts-Amherst) will discusshow GT works in concert with calnexin, calreticulin andsorting receptors to assist in the maturation and quality con-trol on nascent glycoproteins within the ER. Nancy Dahms(Medical College of Wisconsin) will talk on “ building a lyso-some: a story of sweetness and diversion”. She will presenther work on the mechanism by which the two mannose 6-phosphate receptors (CD-MPR and CI-MPR) function aslectins to deliver newly synthesized lysosomal enzymes fromthe secretory pathway to lysosomes.

Extrace l lu lar Matr ix Funct ionCell Contact with extracellular matrix is critical for the ter-

minal differentiation of many cells. In the peripheral nerv-ous system terminal differentiation and myelination bySchwann cells requires contact with basal lamina matrix of aspecific molecular composition. David Carey (Weis Centerfor Research) will describe data showing critical roles of inter-actions between membrane anchored heparan sulfate pro-teoglycans and heperan sulfate-binding extracellular matrixproteins during myelin assembly. The consequences of cellcontact with extracellular matrix are dependent on the struc-ture of the matrix.

Jean Schwarzbauer (Princeton University) will discuss themechanism of fibronectin fibril formation. This processdepends on interactions between fibronectin and integrin

receptors that activate critical downstream signaling cas-cades. Experiments with cells growing on defined three-dimensional matrices have identified regulatory roles for thecellular microenvironment and requirements for specificintracellular signaling molecules during fibronectin matrixassembly.

Joanne Murphy-Ullrich (University of Alabama-Birming-ham) will discuss the functions of matricellular proteins suchas thrombospondins (TSP) 1 and 2, tenascin-C, and SPARC.These proteins signal through distinct receptors, but inducea common phenotype known as the intermediate adhesivestate, characterized by restructuring of focal adhesions andloss of stress fibers. TSP increases cell motility and activatesanti-apoptotic signals. Thus, matricellular proteins regulatekey processes of tissue remodeling during development andwound healing, with implications for tumor metastasis.

Dr. Carlos Hirschberg



microscopy. Linda Hsieh-Wilson fromCaltech integrates organic chemistrywith neurobiology to explore thechemical basis of brain processes suchas neuronal growth and communica-tion. Tom Kodadek from Universityof Texas Southwestern Medical Schoolhas been developing small moleculetools for proteomics, most notably forelucidating the architecture of multi-protein complexes in cells.

New Targets for DrugD iscoveryChair: Carolyn Bertozzi, UC Berkeleyand HHMI

The sequencing of the humangenome as well as the genomes ofmany human pathogens has led toexplosive growth in the identificationof novel macromolecular targets fortherapeutic intervention. Chemistry isplaying an increasingly important rolein not just lead identification andoptimization but also in target valida-tion. This symposium will highlightsome of the challenges encountered insmall molecule approaches to interro-gate new molecular targets for therapy.Jeffery Kelly at Scripps discovers andanalyzes small molecules that modu-late protein translation, protein fold-ing and protein degradation. Theirwork has implications for the treat-ment of a variety of amyloid diseases.James Wells, who recently movedfrom Sunesis Pharmaceuticals to UCSF,explores the science and technologyof drug discovery especially as it per-tains to therapeutically important pro-tein-protein interactions. Carolyn

Bertozzi at UC Berkeley investigatesthe potential utility of chemicallyaltered carbohydrates in the diagnosisand treatment of cancer and in funda-mental studies of glycopathology.

Next Generat ionTherapeut icsChair: Stephen Friend, Merck

In addition to breaking new clinicalground, prototypical drugs have aprofound impact on biochemical andpharmacological investigations intodisease pathogenesis. These funda-mental investigations in turn spawnthe discovery of superior next-genera-tion therapeutic agents. For example,although tubulin binding agents havebeen a rich source of anticanceragents such as taxol and the vincaalkaloids, the pharmacological attrac-tiveness of cytoskeletal proteins isonly just beginning to be appreciated.Timothy Mitchison at Harvard Med-ical School discovers and studies drug-like small molecules that targetinnovative steps in cytoskeletal regu-lation. Kevan Shokat’s research isfocused on the discovery of new lig-ands for modulating signal transduc-tion in cells. Stephen Friend and hiscolleagues at Merck use DNA chips to

hemical Genetics, whichrefers to the study of biologi-cal mechanisms using chem-

ical tools and principles, has emergedas a distinct field at the interface ofbiology and chemistry. Although thefundamental focus of the field is onunderstanding biological phenom-ena, it has direct relevance to practi-cal pursuits, most notably drugdiscovery. This symposium seeks tohighlight some of the rapidlyexpanding frontiers in ChemicalGenetics. The four symposia of thistheme will cover topics of small mol-ecule tools for biology, elucidation ofnew targets for drug discovery, identi-fication of improved next-generationtherapeutic agents, and antibioticbiosynthesis.

Smal l Mo lecu le Too lsfor B io logyChair: Tom Kodadek, UT Southwestern

Although small molecules have fre-quently played a critical role in biologi-cal studies for most of the 20th

century, the genomics revolution hasspawned an urgent need for suchreagents. At the same time new syn-thetic methods have facilitated rapidemergence of large, diverse libraries ofchemicals as well as efficient structuralvariations of biologically active mole-cules. This symposium seeks to illus-trate the power of small molecule toolsin modern biological science. TarunKapoor from Rockefeller Universityexplores the biology of cell divisionusing novel small molecule agents and real-time multi-dimensional

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Chemical Genet ics and Drug DiscoveryOrgan izers : Cha i tan Khos la , S tanford Un ivers i ty, and Kevan Shokat , UCSF and HHM I .

Dr. Kevan ShokatDr. Chaitan Khosla



attend the meeting so that I couldmeet with three prospective postdoc-toral mentors, and presenting a paperwas a requirement for being sent fromas far away as Seattle. However, ourfirst child was expected the previousweek. When the abstract submissiondeadline arrived, I swallowed hardand sent one in, guaranteeing myabsence from home at what mighthave been a critical time. Fortunately,our son arrived on the scheduleddate, we had lots of help from bothnew grandmothers, and I was able toget away long enough to give my talkand be interviewed by three distin-guished scientists.

My first JBC paper was published asthe result of an “introductory” problemsuggested by my Ph.D. adviser, FrankHuennekens, when I began work in hislab in 1959. Dihydrofolate reductasehad recently been discovered, and hesuggested using it for preparative-scalesynthesis of the biological stereoisomerof tetrahydrofolate. The project wentsmoothly, including my one and onlyuse of a polarimeter. After eight or ninemonths, I presented the data to Frank,thinking that I could now move on tosomething important. Frank lookedexcited, and within a week he hadcompleted a manuscript that was pub-lished in the JBC in November 1960. Tomy surprise, I have seen citations tothat paper as recently as the past coupleof years.

My first “lecture” at an ASBMBmeeting was actually a ten-minutetalk at an ASBC meeting, part of anAtlantic City Federation meeting, inApril 1961. In the years before postersessions, the meeting consisted ofmultiple simultaneous sessions, eachbroken into 15-minute blocks—10 forthe talk, 5 for discussion. I wanted to

study the effects of old and new drugson cells with the goal of not justexpanding the range of availabledrugs but also optimizing therapy forindividual patients.

B iosynthes is ofComplex Mo lecu lesChair: Chaitan Khosla, StanfordComplex natural products such asantibiotics represent the pinnacle ofsynthetic elegance and biologicalactivity. They have provided theinspiration for development of muchof modern synthetic organic chem-istry. At the same time many pivotalcellular processes have been eluci-dated as a result of the discovery ofantibiotics with novel biologicaleffects. Yet, for most of the 20th cen-tury, the biosynthesis of these mole-cules has remained a mystery. Theapplication of molecular genetics haschanged that over the past twodecades. Suzanne Walker from Har-vard Medical School will discuss howmicroorganisms make complex car-bohydrate bearing structures such aspeptidoglycan and glycosylatedmacrolide antibacterials. RobertStroud from UCSF will presentinsights into the structural biology ofpolyketide synthases responsible forantibiotic biosynthesis. ChaitanKhosla investigates the biosyntheticmechanisms of polyketide synthaseswith the concomitant goal of provid-ing new tools for the natural productmedicinal chemist as well as forexpanding the repertoire of naturalproduct libraries.

AS BM B ReminiscencesAs part of our Centennial Celebration, we recently asked members to contribute

reminiscences of their early thoughts about becoming a scientist, their experienceas postdocs, their first paper published, their first lecture at an ASBMB Meeting,the friendships and connections they formed with other ASBMB members, theirimpressions of the first ASBMB meeting they attended, and anything else theythought pertinent. Here is the first such contribution received. We believe you willfind it interesting, and we look forward to receiving and publishing more reminis-cences. Please send to them to [email protected].

Dr. Christopher K. Mathews, DistinguishedProfessor Emeritus, Department of Biochem-istry and Biophysics, Oregon State University



phage T7 replication system, to bedescribed by Dr. Charles Richardson inhis Opening Lecture as the recipient ofthe Herbert Tabor/ JBC Award. Dr.Nancy Nossal (NIH) will present herstudies on the architecture and func-tion of the phage T4 replication fork,which represents an important modelof cellular systems. Dr. John Kuriyan(UC Berkeley, HHMI) will provide astructural view of the function of slid-ing clamps and clamp loaders in pro-cessive DNA replication.

Or ig ins andRegu lat ion

DNA replication is tightly controlledat the level of initiation at origins, andalso by checkpoints enabling a varietyof repair processes before reinitiation.Dr. Joyce Hamlin (Univ. Virginia) willchair this symposium and present herpioneering research on the complexstructure of mammalian origins. Dr.David Clayton (HHMI) will discuss newapproaches to the study of replicationof mammalian mitochondrial DNA. Dr.Anindya Dutta will describe the processof replication initiation and its regula-tion in normal and cancer cells.

I nh ib i tors of DNATransact ions

The interface between basic andapplied biochemistry will be exploredin this symposium chaired by Dr. EddyArnold (Rutgers). Dr. Arnold will pres-ent his innovative approach to con-

fronting anti-AIDSdrug resistance bytargeting the poly-merase and RNaseH activities of HIV-1 reverse transcrip-tase. Dr. CharlesMcHenry (Univ.Colorado HealthSciences Center) will present a novelchemical genetic approach using mul-tiplicative target screens to identifyinhibitors of bacterial DNA replication.Dr. Gregory Verdine (Harvard) will dis-cuss a structural approach to studybase excision repair.

Genome Stab i l i ty andD ivers ity : Repa ir andRecombinat ion

Genome management and manipula-tion will be the focus of this symposiumchaired by Dr. Samuel Wilson (NIEHS).Dr. Wilson will extend the discussion ofexcision repair in a presentation describ-ing its strategic regulation through struc-tural and chemical biology. Dr. NancyCraig (Johns Hopkins, HHMI) will dis-cuss the dynamics of transposable ele-ments, and Dr. Dale Wigley (LondonResearch Institute) will present hisresearch on the structure and mecha-nism of the bacterial recombinationmachine RecBCD. The symposium willbe preceded by a plenary lecture by Dr.James Berger (UC Berkeley), who is therecipient of the 2006 Schering-PloughResearch Institute Award.

ur view of DNA as the geneticblueprint of the cell hasexpanded greatly in recent

years with a new understanding of thediversity of genome dynamics. Thistheme will explore mechanisms andregulation of DNA replication, and cel-lular strategies for maintaining geneticintegrity and imparting diversity viaDNA repair and recombination.Research representing a dual focus onprotein machines and DNA sequenceand structures will draw from cellular,mitochondrial and viral systems. Anovel session on inhibitors of DNAtransactions will provide a link to thetheme on Chemical Genetics and DrugDiscovery. Invited speakers will presentbiochemical, genetic and structuralstrategies to address current problems,and each session will be expanded bythe selection of three additional speak-ers from submitted abstracts. Thetheme will also include an interactiveposter session and an informal recep-tion to provide forums for lively scien-tific and social exchange amongparticipants at all levels.

Rep l icat ionAssembl ies andMechan isms

The diversity of DNA replicases andreplication mechanisms will be high-lighted in this symposium chaired byDr. Laurie Kaguni. Kaguni will discussthe mitochondrial replisome and itsstriking parallels with the bacterio-

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Genome Dynamics: Replicat ion, Repair and Recombinat ion

Organ izer : Laur ie S . Kagun i , M ich igan State Un ivers i ty

Dr. Laurie Kaguni



for the replication of a chromosome.The lab combines structural studies ofthe proteins, their functional sub-assemblies, and the replisome itself,with genetic and biochemical analysesof the reactions they mediate. An essen-tial component is defining the protein-protein interactions that coordinate theindividual steps of replication.

BackgroundIn recent years considerable progress

has been made in understanding thereactions catalyzed by the proteins ofDNA replication. However, many ques-tions remain concerning the functionof individual proteins, aside from themore complex processes of initiationof replication at chromosomal originsand the coordination of events at areplication fork.

Even in the case of DNA polymerases,where the wealth of enzymatic datagathered over the years can now be inter-preted in light of the three dimensionalstructures of the proteins, questions per-taining to the basis of nucleotide selec-tion and the coordination ofproofreading with polymerizationremain. Likewise, the mechanism of uni-directional movement of the DNA heli-case on a DNA strand and theunwinding of the duplex are unsolved.Also in need of additional characteriza-tion are the DNA primases, an intriguingclass of enzymes whose zinc motif playsan essential role in sequence recognition.

Even single-stranded DNA bindingproteins, often relegated to mundaneroles, are emerging as key componentsin coordinating reactions at origins andreplication forks. More complex are theinteractions of the helicase and primase

with one anotherand their interac-tion, in turn, withthe polymerasewhere helicase andpolymerase move-ment must be coordinated andprimers transferredto the polymerase. Least well under-stood are the coordination of leadingand lagging strand synthesis and therecycling of the polymerase from oneOkazaki fragment to a new primer.

The Bacter iophage T7Rep l icat ion System

In order to address these questions ofDNA replication the Richardson labora-tory has focused on the replication sys-tem derived from Escherichia coliinfected with bacteriophage T7. The T7chromosome is replicated in a fashioncharacteristic of more complex bacter-ial and eukaryotic systems. Initiation ofreplication occurs at a primary origin,replication is bi-directional, and laggingstrand DNA synthesis is dependent onmultiple initiation events.

Consequently, T7 DNA replicationrequires a processivity factor (E. colithioredoxin) for the DNA polymerase(T7 gene 5 protein), a helicase-primase(T7 gene 4 protein), a single-strandedDNA binding protein (T7 gene 2.5 pro-tein), and other accessory proteinssuch as a 5’ to 3’ exonuclease (T7 gene6 exonuclease) and a DNA ligase (T7gene 1.3 protein). T7 has evolved anefficient and economical mechanismfor the replication of its DNA, one thatprobably defines the minimal require-

harles C. Richardson has beenselected to receive the 2006Herbert Tabor/Journal of Bio-

logical Chemistry Lectureship Award.This award will be conferred at the2006 ASBMB annual meeting, whichalso marks the centennial of ASBMBand its foundation publication, theJournal of Biological Chemistry. Themeeting will be held in conjunctionwith Experimental Biology, April 1-5,2006 in San Francisco, and the HerbertTabor/JBC Lecture will open the meet-ing on Saturday, April 1 at 7 p.m.

The Lectureship was established inrecognition of the many contributionsof Herbert Tabor to the Journal of Bio-logical Chemistry and the Society. Theaward honors the conferee with a cashprize as well as paid travel andexpenses to present a lecture at the2006 meeting. Past recipients of theaward were Robert J. Lefkowitz in2004, and Michael S. Brown andJoseph L. Goldstein in 2005.

Richardson, Professor in HarvardMedical School’s Department of Biolog-ical Chemistry and Molecular Pharma-cology, has been a pioneer in the areaof DNA replication for over 40 years,and continues to publish seminal worktoday. As an acknowledged leader inthe field, he has been a member of theNational Academy of Sciences since1983. He served two terms on the Edi-torial Board of the JBC, and two termson the Nominating Committee of theASBMB. He has also served as AssociateEditor/Editor of the Annual Review ofBiochemistry for over 30 years!

The Richardson Lab’s goal is to under-stand molecular mechanisms thatmediate the multiple reactions required

Charles Richardson to Receive Herbert Tabor/J BC Award

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Continued on page 25

Dr.Charles Richardson


viduals and the policies of institutionsbecause these factors make a differenceand can be changed.”

The article identified results fromparticipants in the ADVANCE Institu-tional Transformation Program, whichthe authors say “appear to work.”

To address the pipeline shortage, forexample, Georgia Tech Engineeringand ADVANCE Professor JaneAmmons, has developed a “speedmentoring” workshop, in which juniorfaculty consult for 15 to 20 minuteswith experienced, tenure-case review-ers to learn ways to strengthen theirodds with tenure committees.

Meanwhile, the University of Michi-gan’s ADVANCE program hosts work-shops that include an interactivetheater program that portrays typicalacademic situations, such as hiring,retention, and climate for women fac-ulty in the sciences and engineering, toraise awareness of personal thoughtsand behaviors that affect the campusclimate toward women faculty.

Workshops at UW-Madison trainmembers of search committees ingood search methods and sensitize theparticipants to bias.

Although systematic examinationand critique of pipeline problems, cam-pus climate, unconscious bias andwork-family juggling can be “disquiet-

ing,” the report says, it is necessary tocreate a “scientific community reflectiveof the pluralist society that supports it.”

In addition to Handelsman,authors of the paper include NancyCantor, chancellor and president ofSyracuse University; Molly Carnes, aUW-Madison Medical School profes-sor and co-director of the Women inScience and Engineering LeadershipInstitute; Denice Denton, chancellorof the University of California atSanta Cruz; Eve Fine of the Womenin Science and Engineering Leader-ship Institute; Barbara Grosz, Hig-gins professor of natural sciences,Harvard University; Virginia Hin-shaw, provost and executive vicechancellor at the University of Cali-fornia at Davis; Cora Marrett, seniorvice president of the University ofWisconsin System; Sue Rosser, deanof the Ivan Allen College of LiberalArts at the Georgia Institute of Tech-nology; Donna Shalala, president ofthe University of Miami; and Jen-nifer Sheridan of the Women in Sci-ence and Engineering LeadershipInstitute at UW-Madison.

The National Science Foundation(NSF) is an independent federalagency that supports fundamentalresearch and education across allfields of science and engineering,with an annual budget of nearly$5.47 billion. NSF funds reach all 50states through grants to nearly 2,000universities and institutions. Eachyear, NSF receives about 40,000 com-petitive requests for funding, andmakes about 11,000 new fundingawards. The NSF also awards over$200 million in professional and serv-ice contracts yearly.

espite gains over recent yearsin the number of womenwho receive Ph.D.’s in science

and engineering fields, a relative fewgo on to assume high-level facultypositions. Writing in the August 19issue of the journal Science, several topwomen scientists and universityadministrators attributed the imbal-ance to four pervasive elements:❖ small numbers of women in the fac-

ulty pipeline ❖ a hostile or “chilly” campus climate

toward women junior faculty ❖ unconscious bias that results in

covert discrimination ❖ sacrifices to balance family and work

“While we as a nation have madeconsiderable progress in attractingwomen into most science and engi-neering fields, we still see fewerwomen at the full-professor and aca-demic leadership levels than we wouldexpect...” said Alice Hogan, director ofthe National Science Foundation’s(NSF) ADVANCE program, which aimsto increase the representation andadvancement of women in academicscience and engineering careers.

“After investing in creating this poolof highly trained talent,” she added,“we should see a high rate of return—productive, creative and respectedteachers and researchers attractingmore students into fields that mighthave seemed closed to them given thetraditional profile of science and engi-neering faculty.”

Lead author Jo Handelsman, Profes-sor of Plant Biology at the Universityof Wisconsin-Madison, and her col-leagues focused on the “cultural issuesthat manifest in the behavior of indi-

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More Women Receive Ph.D.’s, But Female Senior Faculty St i l l Rare


n anticipation of the Journal of BiologicalChemistry’s Centennial, we thought it time todress-up the old girl with a complete

“makeover.” JBC has been the leader in science publish-ing innovation, yet the appearance of the Journal hadnot significantly changed in over 30 years. Thechanges, particularly the new cover format, signal thenew excitement about JBC and a fresh start for the next100 years. While the substance of the JBC will continueto be exciting research reports, we have also added sev-eral new features that also mark the Centennial; JBCReflections, on the careers of the world’s leading bio-chemists; JBC Classic Papers, reprinting the mostimportant and influential papers published in the JBCover the past 100 years; and JBC Papers of the Week,some of the most exciting papers published in eachissue of the JBC.

So JBC is not your grandfather’s or grandmother’sOldsmobile any longer.

A New Look for the Journal of Biolog ical Chemistry

I

ments for the rapid and faithful replication of a duplexDNA molecule.

The limited number of proteins involved in T7 replica-tion offers two major advantages: the stoichiometry ofthe proteins in functional complexes is facilitated by thelimited number of permutations, and a determination ofthe three dimensional structure of functional complexesis an achievable goal..

Several examples illustrate the simplicity of functionalcomplexes in the T7 replication system. Thioredoxin,the processivity factor, binds to the polymerase to clampthe complex onto a primer-template. Economy dictatesthat the polymerase provide one-half the clamp; assem-bly occurs without accessory proteins, in contrast to thesituation in E. coli and phage T4 . Similarly, the T7 gene4 protein provides both helicase and primase activitiesat the replication fork whereas in other systems theseactivities are provided by separate proteins.

The experimental utility of a limited number of pro-teins is most apparent in studies on the T7 replisome.The Richardson lab has constructed a T7 replisome, con-sisting of only four proteins, that fulfills all of the predic-tions that arise from models of coupled leading andlagging strand synthesis.

Tabor/J BC Award cont inued …Continued from page 23

Call for AbstractsThe submission site is now open

www.asbmb.org Abstract Submission Deadline: November 2, 2005

ASBMB Travel Award Application Deadline:

October 21, 2005

ASBMB & JBC Annual Meeting & Centennial Celebration April 1-5, 2006 • San Francisco, CA


used the Flinders Sensitive Line rats toinvestigate the link between omega-3fatty acids and depression. They exam-ined the brains of the depressed rats andcompared them with brains from nor-mal rats. Surprisingly, they found thatthe main difference between the twotypes of rats was in omega-6 fatty acidlevels and not omega-3 fatty acid levels.Specifically, they discovered that brainsfrom rats with depression had higherconcentrations of arachidonic acid, along-chain unsaturated metabolite ofomega-6 fatty acid.

Arachidonic acid is found through-out the body and is essential for theproper functioning of almost everybody organ, including the brain. Itserves a wide variety of purposes, frombeing a purely structural element inphospholipids to being involved in sig-nal transduction and being a substratefor a host of derivatives involved insecond messenger function.

“The finding that in the depressiverats the omega-3 fatty acid levels were

group of researchers fromIsrael has discovered that ratsexhibiting the signs of depres-

sion have increased levels of theomega-6 fatty acid, arachidonic acid,in their brains. The details of theirfindings appeared in the June 2005issue of the Journal of Lipid Research(2005, 46: 1093-1096), an AmericanSociety for Biochemistry and Molecu-lar Biology journal.

During recent years, omega-3 fattyacids have enjoyed increased popular-ity as numerous studies have shownthat supplementing diets with fish oil(a natural source of this polyunsatu-rated fatty acid) does everything fromreducing the risk of heart disease topreventing arthritis. There is also evi-dence that depression may be associ-ated with a dietary deficiency inomega-3 fatty acids. This “phospho-lipid hypothesis” of depression hasbeen supported by research showingthat omega-3 fatty acid concentrationin the blood of depressed patients islower than that in control patients.

“The ‘phospholipid hypothesis’ ofdepression postulates that decreasedomega-3 fatty acid intake, and hence,perhaps decreased brain omega-3 fattyacid content, could be responsible forthe disease,” explains Dr. Pnina Greenof Tel Aviv University. “In humans,because of high dietary variability andthe obvious inability to examine braintissue, the theory is backed up mainlyby indirect evidence. The availabilityof the Flinders Sensitive Line rat, ananimal model of depression, over-comes both these obstacles.”

In the Journal of Lipid Research study,Dr. Green in collaboration with Dr. GalYadid of Bar-Ilan University, Ramat Gan,

A

Study Links Brain Fatty Acid Levels to DepressionBy N ico le Kresge , Staf f Sc ience Wr i ter

AS BM B WelcomesNew Ph.D.s

ASBMB extends its congratula-tions to these individuals whorecently received their Ph.D.degrees. In recognition of theirachievement, ASBMB is presentingthem with a free one-year member-ship in the Society. The new Ph.D.sare listed below with the institutionfrom which they received theirdegree.

Weihong HouMedical College of Zhengzhou University

Guofun ZhaoUniversity of Tennessee, Knoxville* Candidates with an asterisk were previous Associ-ate members who met the requirements for a free

one-year membership.

not decreased, but arachidonic acidwas substantially increased as com-pared to controls is somewhat unex-pected,” admits Dr. Green. “But thefinding lends itself nicely to the theorythat increased omega-3 fatty acidintake may shift the balance betweenthe two fatty acid families in the brain,since it has been demonstrated in ani-mal studies that increased omega-3fatty acid intake may result indecreased brain arachidonic acid.”

Although far less attention has beenpaid to dietary requirements foromega-6 fatty acids, which can befound in most edible oils and meat,perhaps in the future depression maybe controlled by increasing omega-3fatty acid intake and decreasingomega-6 fatty acid intake.


inhibiting ATF2, it became more sensi-tive to treatment,” Ronai said. Conse-quently, his laboratory developed asmall peptide that interferes with ATF2function, efficiently blockingmelanoma growth in mouse models.Ongoing studies are devoted to screen-ing for compounds that mimic thepeptide’s actions and to allow for fur-ther development of the peptidetoward clinical assessment.

“Until our recent studies, we werecertain that the mechanism by whichATF2 affects melanoma growth wasprimarily through its established func-tion in the regulation of proteinsimportant in cell cycle and cell deathcontrol. We were therefore most sur-prised to find an uncoupled functionfor the same protein,” said Ronai.

The finding of ATF2’s novel functionin DNA repair was serendipitous. AsShoichi Takahashi, a postgraduateresearcher, was testing for the changesin ATF2 in human cancers, he “lost thesignal” for ATF2. “Later,” Dr. Ronai said,“we did experiments that showed thesignal was lost because a protein kinase,ATM, modified ATF2 enough to inter-fere with detection of the ATF2 signal.Soon, work performed by AninditaBhoumik confirmed that ATF2 is regu-lated by ATM and that this regulation iscentral to the cell’s ability to initiateDNA repair processes following ionizingirradiation or other exposures that causebreaks in DNA. A likely way in whichATF2 works is to halt the cell’s cycle toallow repair of damaged DNA beforesuch damage results in mutation.”

Ronai and his colleagues are nowdetermining how molecules like ATF2

can balance their dual roles. “Highdoses of radiation, as well as changesthat take place in cancer and patho-logic situations, can activate both func-tions of ATF2, which is expected todisturb the otherwise conserved bal-ance between its role in gene regulationand the DNA damage response. Weneed to find out which of the two func-

tions is more dominant under these cir-cumstances in order to devise ways toregain the proper balance,” he said.

The Ronai lab’s work on ATF2 wasstarted at Mount Sinai School of Medi-cine in New York City, from which DrRonai and his colleagues recently relo-cated to the Burnham Institute. Thisstudy was carried out in collaborationwith Wolfgang Breitweiser and NicJones of the Paterson Institute forCancer Research, Manchester, Eng-land, and Yosef Shiloh, of Tel AvivUniversity, Israel. The study was sup-ported by a grant from the NationalInstitutes of Health.

*ASBMB Member

Burnham Institute study hasfound that a protein knownfor its role in gene regulation

has another important function, thatof initiating DNA repair. The study,published in the May 27, 2005 editionof Molecular Cell, points to new targetsfor the treatment of cancer.

Ze’ev Ronai,* Director of the Insti-tute’s Signal Transduction Program,and his colleagues found that the pro-tein ATF2 (Activating TranscriptionFactor-2) is activated by a proteinkinase called ATM (Ataxia-Telangiecta-sia Mutated), which stimulates DNArepair. ATF2’s role in regulating expres-sion of proteins that control cell cycleand programmed cell death is wellestablished. The current study is thefirst to demonstrate ATF2’s role in DNArepair, an intracellular process that pre-vents formation of genetic mutations,including those that lead to cancer.

“This is the first time we’ve seen aprotein which has been implicated ingene regulation possess an independ-ent function—in DNA repair—whileboth functions are independent fromone another,” said Ronai. Dr. Ronai’slaboratory has been studying ATF2with the goal of understanding its rolein regulation of cell cycle and pro-grammed cell death. These studiesevolved from the finding that ATF2has an important role in the develop-ment and progression of melanomatumors. Inhibition of ATF2 was foundto sensitize melanoma to various treat-ments, both in tissue culture and inanimal models.

“Melanoma is usually resistant tochemotherapy, but we found that by

New Understanding of DNA RepairMay Pave Way to Cancer TreatmentsA

Thi s i s th e f i r s t t imew e ’ v e s e en a p ro t e inw h i ch ha s b e enimp l i ca t ed in g en ere gu la t i on p o s s e s s anindep endent f un c t i on —in DNA rep a i r—whi l ebo th f unc t i ons a reindep endent f rom on ea nothe r.

— Ze’ev Ronai

B I O T E C H B U S I N E S S N E W S


by John D . Thompson , Ed i tor

Sales of Biogenerics in US,

More than 7,000 new jobs and nearly90 new businesses could be created overthe next 10 years if all the plans in aRegional Bioscience Strategic Planunveiled last month by the Greater Okla-homa City Chamber come to fruition.

The Chamber hired Battelle’s Technol-ogy Partnership Practice, a worldwideleader in research and developmentactivity with more than 1,000 clientsand 4,500 projects annually, to helpdevelop the plan. The Chamber alsoworked with a Steering Committee ofmore than 20 science and business lead-ers in the region during the course of thenine-month project.

“We discovered that our region hassome very strong pockets of scientificresearch, a growing foundation of bio-

science companies and state-of-the-artfacilities with room for expansion thatmany larger markets don’t haveaccess,” said Greater Oklahoma CityChamber President and CEO RoyWilliams. “Our potential for continuedsuccess in bioscience is great; however,we must create new resources as well asbetter leverage our existing assets torealize this potential.”

The Oklahoma City project seeks todiversify the region’s economic base,provide high-end, well paying jobs andcontribute to the overall economic pro-ductivity. In 2003, the bioscienceindustry paid more than $15,000 abovethe average annual wage for the region.All 14 action items revolve around fourproposed strategies to take the region’sbioscience cluster to the next level:❖ Build the region’s bioscience

Research and Development base andencourage commercialization of bio-science discoveries;

❖ Develop and attract bioscience talentto the region;

❖ Grow a critical mass of biosciencecompanies by creating an environ-ment in which such firms can start,grow and prosper;

❖ Build a bioscience image and marketthe region.More than 100 scientists, business

people and service providers wereinterviewed for the strategic plan. Inaddition to the interviews, there wasextensive economic research, focusgroup sessions, benchmarking againstsix comparable markets, identificationof key scientific strengths and recom-mended strategies, actions and fund-ing items for future implementation.

Battelle discovered that 99% of theresearch and development in biosciencesin Oklahoma occurs along the Interstate35 corridor extending from Stillwater in

Oklahoma City Unveils Reg ional Strateg ic Bioscience Planthe north, through the Oklahoma Cityarea to Ardmore in the south. Chamberofficials brought in Battelle to help definethe region, identify partners and targetpotential collaborators.

Walter Plosila, Vice President for Bat-telle, said the Greater Oklahoma Cityregion has several important buildingblocks for success in biosciences. “Thereare first-rate facilities at the PresbyterianHealth Foundation Research Park; thereare quality scientists at University ofOklahoma Health Sciences Center,Oklahoma Medical Research Founda-tion, Oklahoma State University, NobleFoundation and the University of Okla-homa in Norman; and the state hasmodel service providers like the Okla-homa Center for Advancement of Sci-ence and Technology and i2E (TurningInnovation into Enterprise).”Oklahoma City Not Alone In

Hunt for Biotech BusinessMarket capitalization of biotechnol-

ogy in the United States grew 17% lastyear and states across the country areinvesting significant dollars in bio-science. Following are just a few recententries in what might be called theBiotech Sweepstakes.❖ Iowa has started a 10-year, $500 mil-

lion Grow Iowa Values fund, whichincludes Biosciences;

❖ Kansas has the Kansas EconomicGrowth Act, a $500 million, 10-yearinvestment to encourage biotechnol-ogy and entrepreneurship;

❖ In Washington, $350 million will beallocated over a 10-year periodbeginning in 2008 to a Life SciencesDiscovery Fund to grow the bio-science industry and ensure compet-itiveness of its research institutions;

❖ Wisconsin has developed a 10-year,$375 million plan for an Institute forDiscovery in Madison.

Copies of expensive biotech drugscould hit $16.4 billion in sales in theUnited States and Europe by 2011once regulatory curbs on so-called bio-generics use are gone, according to astudy released in early September..

The study by the global consultinggroup Frost & Sullivan noted that tra-ditionally, biotech drugs made usinggenetic engineering have beenimmune from generic competition,since regulators in these major marketshave been slow to set clear approvalrules and many are still patent-pro-tected. However, the Frost & Sullivanstudy’s analysis found that the outlookfor biogenerics is fast improving.

“As regulatory guidelines are intro-duced over the next two to threeyears and some of the biggest bio-pharmaceutical blockbusters losepatent protection, the biogenerics


Greater Philadelphia to 10 other metro-politan areas considered the leading lifesciences clusters in the U.S. and ranksthem based on employment, output,workforce, investment and dozens ofother measures. Following is theMilken Institute Life Sciences Compos-ite Index ranking (with scores):

1. Boston (100) 2. Greater San Francisco (98.4)3. Greater Philadelphia (97.1)4. Greater New York (94.6)5. Greater Raleigh-Durham (91.1)6. San Diego (90.7)7. Greater Los Angeles (87.0)8. Minneapolis (77.9)9. Chicago (75.9)10. Seattle (70.9)11. Dallas (55.2)

The core life sciences industry—which includes biotechnology, phar-maceuticals, medical devices andresearch and development in life sci-ences—is sought after by local eco-nomic development organizationsacross the country for its high-payingjobs and tremendous growth potentialbased on expected pending break-throughs in medical research and anaging baby boomer population.

Institute researchers used more than60 core measurements to create the LifeSciences Composite Index. The maincriteria (both weighted 50 percent)were the Institute’s InnovationPipeline, which measures the assetsthat allow a metro to capitalize on itslife sciences knowledge and creativity,such as the quality of its workforce; andCurrent Impact Assessment, whichmeasures an area’s success in bringingresearch ideas to the marketplace andcreating companies, jobs and products.

Among the findings: On the Innovation Pipeline Index,

Boston placed first, followed by

Greater San Francisco, GreaterPhiladelphia and San Diego.

On the Current Impact Assessment,Philadelphia placed first, followed byNew York, San Francisco and Boston.

New York employed the most lifesciences workers of the 11 clusters(74,592 in 2003), followed by Philadel-phia (53,479), Greater Los Angeles(51,533) and San Francisco (46,593).

Life sciences employment (relativeto the national average) grew fastestfrom 1997 to 2003 in Greater RaleighDurham (19.3% above the nationalaverage), followed by Philadelphia (+9.3%) and Minneapolis (+ 0.6%).

Within the Current Impact Assess-ment, the leaders in the four mainindustries studied were Philadelphia(pharmaceuticals), Minneapolis (med-ical devices), Raleigh Durham(biotechnology) and San Diego (lifesciences R&D).

Supporting industries such as hospi-tals and medical schools employedmore than 912,000 workers in NewYork in 2003, the most of any of theclusters measured. Los Angeles was sec-ond with more than 472,000 andChicago third with over 395,000.

The report also includes a section onthe so-called “multiplier impact” of thelife sciences industry on the broaderPhiladelphia economy. According tothe study, life sciences is responsiblefor $15.5 billion (7.1 percent) of theregion’s gross metro product, $6.9 bil-lion directly and $8.6 billion from theeconomic impact in other industries.

In addition to highlighting many ofPhiladelphia’s strengths, the study alsopointed out opportunities for improve-ment, such as increasing support forlife sciences startup firms throughgreater availability of risk capital and astronger support infrastructure.

If the life sciences industry is theholy grail of economic development,as many public policy officials believe,then Boston, Greater San Francisco,Greater Philadelphia and Greater NewYork are in the best position to gainfrom this dynamic industry in theyears to come. The four regions rankedat the top of the Milken Institute’s LifeSciences Index, a measure of not onlythe current strength of these clusters,but their growth potential.

“The life sciences industry is anemerging powerhouse for U.S. globaleconomic competitiveness in the 21stcentury,” says Ross DeVol, Director ofRegional Economics at the Milken Insti-tute and principal author of the report.

The report, The Greater PhiladelphiaLife Sciences Cluster: An Economic andComparative Assessment, compares

Boston, San Francisco, Philadelphia Top Life Sciences Clusters in U.S.

Europe Expected to Soarmarket is expected to see exceptionalgrowth and rapidly reach billion-dol-lar levels,” said Frost & Sullivan ana-lyst Himanshu Parmar.

Generic drug makers are keen totap into the market by producingcheaper versions of products such ashuman growth hormone, transgenicinsulin and erythropoietin (EPO), the“blood boosting” medicine.

Frost & Sullivan said products likethese could reach markets in NorthAmerica and Europe by 2006-07 andpotentially generate sales of $16.39billion by 2011.

Although no generic version of abiotech medicine has yet beenapproved, Europe is further aheadthan the United States in the matter,having already established a legalframework for “biosimilar” drugapplications.

B I O T E C H B U S I N E S S N E W S


infectious agents, such as the SARSvirus, or man-made threats like anattack using a dangerous biologicalagent,” said Georges Benjamin, execu-tive director of the American PublicHealth Association and chair of thecommittee that wrote the report. “Nosingle entity currently has the respon-sibility, authority, and resources toorchestrate all the activities of thequarantine system, and the traditionalresponsibilities of quarantine person-nel are no longer sufficient to meet thechallenges posed by the rapidlyincreasing pace of global trade andtravel and the emergence of newmicrobial threats. Consequently, werecommend the establishment of clearleadership and lines of communica-tion among all parties involved in pro-tecting the public from infectiousagents that originate abroad.”

Every year, roughly 120 millionpeople travel into or out of the coun-try through the nation’s 474 airports,seaports, and land-border crossings.In 2003 Congress began to allocatefunds to bring the number of quaran-tine stations from eight to 25. The 25cities that would comprise theexpanded quarantine station systemtogether receive more than 75 millioninternational travelers and immi-grants annually and 31% of the cargoimported by sea. Currently, just11quarantine stations staffed by CDCpersonnel are fully active in majorpoints of entry.

A national strategic plan devised byCDC quarantine personnel is neededto provide the best possible frameworkfor protecting the public from theimportation of dangerous biologicalagents, the committee concluded.

he system for interceptingmicrobial threats at thenation’s airports, seaports, and

borders needs strategic leadership and acomprehensive plan to meet the chal-lenges posed by emerging diseases andbioterrorist threats, says a new reportfrom the Institute of Medicine of theNational Academies. The report recom-mends that the Centers for DiseaseControl and Prevention, particularly itsDivision of Global Migration and Quar-antine and individual quarantine sta-tions at U.S. ports of entry, should havethe responsibility, authority, andresources to lead the effort to protectthe public from microbial threats.

“CDC quarantine stations and thebroader quarantine system serve as thenation’s insurance policy against catas-trophes that might arise from theimportation of naturally occurring

T

IOM Sees Flaws in Protect ionAgainst Bioterrorism Agents

The ASBMB/Centennial Clara Benson Travel Fellowship AwardIn honor of the Centennial Celebration of ASBMB and the Journal of Biological Chemistry

The ASBMB has established five travel fellowships inhonor of Clara C. Benson, the only woman in the group of81 scientists who founded the American Society forBiological Chemists in December, 1906. The fellowshipswill be awarded to female biochemists and molecularbiologists in the early stages of their careers (postdoctoralfellows and junior faculty members or scientists not morethan five years after the date of PhD graduation). Nomineeswill be selected based on their scientific contributions tobiochemistry and molecular biology, and their potential forcontinuing a high level of scientific endeavor. The travelfellowship recipients will receive a plaque and up to $2,500towards their travel expenses to attend the ASBMBCentennial Meeting in San Francisco, to include travel,hotel, meals and Early-bird meeting registration.

To nominate a candidate for the Clara Benson Travel FellowshipAward the following materials must be uploaded as MS Word orPDF files at the Travel Award section of the ASBMB AnnualMeeting and Centennial webpage, www.asbmb.org/meetings.

●A brief statement providing the focus of the nominee’sresearch

●A copy of the nominee’s successfully submitted abstract●The nominee’s CV●A signed letter of recommendation, on

institution letterhead, from the nominee’sdepartment chair or mentor

●Two additional signed letters of support,on institution letterhead, at least one ofwhich must come from outside thenominee’s current institution

All nominations must be received no later than Friday, October 21, 2005.

Growth, Differentiation and Cancer: S P E A K E R SCo-Chairs Steve Elledge, Vicki Lundblad, Titia de Lange,

Steve Elledge, Charles Sherr Iswar Hariharan

Gene Interactions and S P E A K E R SUnraveling Complex Traits: Aravinda Chakravarti, Allen Orr,

Co-Chairs Trudy Mackay, Peter DonnellyAravinda Chakravarti, Chuck Langley

New Insights in Epigenetic Phenomena: S P E A K E R SCo-Chairs Barbara Meyer, Vicki Chandler,

Art Beaudet, Barbara Meyer Steve Henikoff, Art Beaudet

Stem Cell Genetics: S P E A K E R SCo-Chairs Judith Kimble, Janet Rossant,

Judith Kimble, Janet Rossant Allan Spradling, Liheng Li

Neurological Diseases: S P E A K E R SCo-Chairs Susan Lindquist, Li Hui Tsai,

Susan Lindquist, Jeremy Berg Mario Capecchi, Cynthia Kenyon

Comparative Genomics: S P E A K E R SCo-Chairs Eric Green, Bill Gelbart,

Maynard Olson, Eric Green David Kingsley, Richard Durbin

Technology: S P E A K E R SChair George Church, Ron Davis, Lee Hood

Stan Fields

GSA MEETINGJanuary 5-7, 2006

San Diego, California

Keynote Speakers:Paul Nurse

Mary-Claire KingSydney Brenner

Sign up for this meeting atwww.GSA-MODELORGANISMS.org

Two poster sessions PLUS additional speakers

chosen from abstract submissions!

C a l e n d a r o f S c i e n t i f i c M e e t i n g s


D E C E M B E R 2 0 0 5

Xth PABMB Congress: Panamerican Association forBiochemistry and Molecular Biology

December 3-6 • Hotel del Bosque, Pinamar, Province ofBuenos Aires, ArgentinaFor more information contact:SAIB President. Ernesto Podestá: [email protected] Secretary Carlos Argaraña: [email protected], orPABMB Chairman Juan José Cazzulo: [email protected]: http://www.saib.org.ar

2005 Congress Expanding Proteomics: New Directionsin Biology, Chemistry, Pharmaceutical Sciences andMedicine

December 5-7 • Zurich, SwitzerlandFor information contact: Email: [email protected]; Ph: +41 21 802 1163Website: http://sps05.swissproteomicsociety.org/qsPortal/Home.asp

Cambridge Healthtech InstituteSixth Annual Metabolic Profiling

December 7–8 • Wyndham Palace Resort and SpaContact: Pete DeOlympioPh: 617-630-1359, Email: [email protected]: www.healthtech.com/2005/gfp/index.asp

3rd Cachexia Conference

December 8-10 • RomeFor information contact:Website: www.nataonline.com/LMS-Group/events/2/index.ph

American Society for Cell Biology Annual Meeting

December 12–14 • San FranciscoContact: John Fleischman; Ph: 301-347-9300Email: [email protected]; Website: www.ascb.org

Non-VesicularIntracellular Traffic

December 15-16 • Goodenough College, London, UKContact: Meetings Office, Biochemical Society, 3rd Floor, EagleHouse, 16 Procter Street, London, WC1V 6NXEmail: [email protected]:www.biochemistry.org/meetings/focused.htm

Pacifichem 2005

December 15-20 • HonoluluFor information contact: Website:www.pacifichem.org/Email: [email protected]

O C T O B E R 2 0 0 5

Supramolecular Chemistry

October 14-19 • Obernai (near Strasbourg), FranceA European Science Foundation conference. For information:Ph: +33 (0)3 88 76 71 35; Fx: +33 (0)3 88 36 69 87Email: [email protected]

North Carolina RNA Society’s Symposium on RNABiology VI: RNA, Target and Tool Theme: Small RNAs andRNPs.

October 21-22 • North Carolina Biotechnology Center,Research Triangle Park, NC. 2005 Deadline for registration and abstract submission: July 1Email: [email protected]: http://www.med.unc.edu/pmbb/nc-rna-soc.html

N O V E M B E R 2 0 0 5

International Workshop on Biosensors for Food Safetyand Environmental Monitoring

November 10-12 • Agadir, MoroccoContact: Université Hassan II-Mohammedia, Faculté desSciences et Techniques, B.P. 146, Mohammedia, Morocco Email [email protected]: www.univh2m.ac.ma/biosensors

BioConferences International 6th European Biotechnology Symposium

November 13–15 • Radisson SAS Scandinavia Hotel,CopenhagenContacts: Aimee Burt; 800-524-6266; [email protected] Rivera; 800-524-6266; [email protected]: www.bioconference.com/ebs/

Cambridge Healthtech InstituteSecond Annual Fluorescent Proteins in DrugDevelopment

November 14–15 • Hyatt Regency La Jolla, CaliforniaContact: Pete DeOlympioPh: 617-630-1359, Email: [email protected]: www.healthtech.com/2005/gfp/index.asp

Third Annual World Congress on the Insulin ResistanceSyndrome Clinical manifestations of the InsulinResistance Syndrome - Metabolic Syndrome X

November 17-19 • Palace Hotel, San FranciscoFor information on registration, abstracts submission, accom-modations and exhibits: Ph: 818-342-1889; Fax: 818-342-1538Email: [email protected] : www.insulinresistance.us

M A R C H 2 0 0 6

Gordon Research Conference (GRC) on NewAntibacterial Discovery & Development

March 5-10 • Ventura Beach Marriott, Ventura, CaliforniaFor Information: Email:[email protected]: www.grc.org/programs/2006/antibact.htm

RNAi2006: Advances in RNA Interference Research

March 22-23 • St. Anne’s College, Oxford, UKConference Organizer: Muhammad SohailBiochemistry Department, University of OxfordTel: +44 1865 275225; Fax: +44 1865 275259Email: [email protected]: http://libpubmedia.co.uk/Conferences/RNAi2006HomeMay2005.htm

American Chemical Society 231st National Meeting

March 26 – 30 • AtlantaContact: Charmayne Marsh; Ph: 202-872-4445Email: [email protected]; Website: www.acs.org/meetings

A P R I L 2 0 0 6

American Society for Biochemistry and MolecularBiology Centennial Meeting in Conjunction withExperimental Biology 2006

April 1–5 • San FranciscoFor information contact: www.asbmb.org/meetingsEmail: [email protected]: 301-634-7145; Website: www.asbmb.org/meetings

Recomb 2006 - The Tenth Annual InternationalConference on Research in Computational MolecularBiology

April 2-5 • Venice, ItalyFor information contact:Email: [email protected]: +39 0415238995Website: http://recomb06.dei.unipd.it/

47th ENC Experimental Nuclear Magnetic Resonance

April 23-28 • Asilomar Conference Ctr., Pacific Grove, CAContact: ENC, 2019 Galisteo Street, Building I-1Santa Fe, New Mexico 87505; Ph: 505-89-4573Fx: 505-989-1073; Email: [email protected] page: http://www.enc-conference.org

J A N U A R Y 2 0 0 6

Pacific Symposium on Biocomputing

January 3-7 • Wailea, MauiFor information contact: http://psb.stanford.edu/Email: [email protected]; Phone: (650)725-0659

Building Bridges, Forging Bonds for 21st CenturyOrganic Chemistry and Chemical Biology

January 7-9 • Pune, IndiaTel.: 202-872-4523; Email: [email protected]: http://www.ncl-india.org/occb2006/index.htm

F E B R U A R Y 2 0 0 6

The 11th Annual Proteomics Symposium

February 3-5 • Erskine on the Beach, Lorne, AustraliaEmail: [email protected] www.australasianproteomics.org.au/lorne.htm

The 31st Lorne Conference on Protein Structure andFunction

February 5-9 • Erskine on the Beach, Lorne, Australiaemail: [email protected]; www.lorneproteins.org/

Third International Conference on Ubiquitin,Ubiquitin-like Proteins, and Cancer

February 9-11 • The University of Texas M. D. AndersonCancer Center, Houston, Texas This meeting will celebrate the Nobel Prize awarded to AvramHershko, Aaron Ciechanover, and Irwin Rose for their discov-ery of the ubiquitin pathway and the 10th anniversary of thediscovery of SUMO/Sentrin and NEDD8Application and Abstract Submission Deadline: Friday,November 11, 2005; For information contact: Amy HeatonProgram Manager, Department Of CardiologyUniversity of Texas M. D. Anderson Cancer CenterTel: 713-745-6826; Fax: 713-745-1942 Website: www.sentrin.org

ABRF 2006—Integrating Science, Tools andTechnologies with Systems Biology

February 11-14 • Long Beach, CaliforniaFor Information: www.faseb.org/meetings/abrf2006

G Protein- Coupled Receptors: Evolving Concepts andNew Techniques

February 12-16 • Keystone, ColoradoFor information contact:Ph.: 800-253-0685 / 970-262-1230Email: [email protected]://www.keystonesymposia.org/Meetings/ViewMeetings.cfm?MeetingID=807

Confirmed Speakers: Vytas Bankaitis

Christoph BenningPeter GriacElina IkonenSima LevFred MaxfieldAnant MenonRobert NabiWill PrinzHoward RiezmanRosario RizzutoAlexei TepikinJean VanceDennis Voelker

Organizers: Shamshad CockcroftTim Levine

Biochemical Society Focused Meeting

15–16 December 2005Goodenough College, London, UK

Intracellular traffic of material and information is of fundamental importance to cellfunction. While much attention has focused on transport mediated by vesicles, anotherhighly conserved mechanism exists: non-vesicular traffic. This fulfils essential cellularfunctions by mediating the transport of small molecules in two major categories: lipidsand calcium ions. Despite the distinct natures of lipids and calcium ions, their trafficshares one major feature: it occurs at sites where organelles come into close contact withone another. For example, lipid traffic occurs at stable, purifiable zones of contactbetween endoplasmic reticulum and mitochondria, and it is proposed that calcium fluxalso occurs in close relation to such contact sites. This two-day meeting will be the firstto concentrate on the activities of these contact zones.

Talks will address traffic at zones of contact formed between different organelles, as well as proteins in particular lipid-transfer proteins, that are understood to be involvedin this process.

This meeting will be published in Biochemical Society Transactions.

++Ca

++Ca

Non-vesicular intracellular traffic

Poster Abstract Deadline22 October 2005

Early Registration Deadline15 November 2005

FeesInclude lunches and refreshments

Full member Student Non-member

Biochemical SocietyTransactions 34(3)

Sponsored by:

$368$184$552

$40

www.biochemistry.org/meetings

For further information contact [email protected] or visit

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