Constituent Society of FASEB AMERICAN SOCIETY FOR ... · This process in no way diminishes the interest of NIH Institutes and Centers in investigator-initiated, unsolicited research

w w w a s b m b o r g

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

DECE M BE R 2006DECE M BE R 2006 w w w a s b m b o r g

Constituent Society of FASEB


Garvan InstituteOne of Australiarsquos Largest

Medical Research InstitutionsSee page 18

LIMITED TIME OFFERDecember 1st through midnight December 21st (EST)

Save an extra 10 on every orderPlus get FREE shipping when you spend $25 or more

(see site for details)

Go to wwwbncomasbmbto start your holiday shopping

A Holiday Surprisefor Our Members

HURRY

Limited Time Offer

ASBMB has teamed up with

Barnes amp Noblecom

HolidayGiftIdeas_2006_1bindd 1 112206 12502 PM

f e a t u r e s8 Scientists Reverse Friedreichrsquos Ataxia Defect in

Cell Culture

9 Researchers Uncover Critical Player In Cell Communication

10 Structure of Enzyme Offers Treatment Clues for Diabetes Alzheimerrsquos

11 First Major Study of Mammalian lsquoDisorderlyrsquo Proteins

12 Biomedical Careers in Industry A Few Tips for the Newcomer (Part 1)

14 ASBMB 2007 Enzyme Mechanism and Design

15 From Genome to EpigenomemdashModification and Repair

16 Susan Taylor to Receive William C Rose Award

17 Christopher Burge to Receive Schering-Plough Award

24 Nancy Goldman Nossal N IH Scientist

25 Education and Professional Development

d e p a r t m e n t s2 From the Desk of the President

4 News From the Hill

6 Washington Update

7 NIH News

12 Career Insights

22 Spotlight on Members

26 ASBMB BioBits

28 Biotech Business

30 For Your Lab

31 Career Opportunities

32 Calendar



O N T H E C O V E R

18 Garvan Institute One of AustraliarsquosLargest MedicalResearch Institutions

26

DECEMBER 2006Volume 5 Issue 9

10

BRONZE AWARD WINNER 2003

AWARDS OF EXCELLENCEMOST IMPROVED MAGAZINE

COLUMNS amp EDITORIALS

DESIGN amp LAYOUT

he breakthroughs of sciencecome from unexpectedsources There is substantial

agreement that investigator-initiatedresearch is the discovery engine thathas brought the US biomedicalresearch establishment to its preemi-nent position in the world and hasincreased our prestige in the worldenormously The US commands apredominant position in prizes suchas the Nobel and the Lasker One ofthe major goals of the leadership atASBMB is to ensure that the NIHcontinues to appreciate and fund dis-covery science the science that isdriven by the best judgment andinsight of individual investigatorsThe importance of unfettered inves-tigation on making breakthroughdiscoveries is exemplified by the win-ners of this yearrsquos Nobel Prizes inChemistry and Medicine

As you have been repeatedly hear-ing from me there has been an alarm-ing trend toward NIH-solicitedresearch during the period of the dou-bling of the NIH budget For examplewhile the NIH budget increased 24-fold from 1996 to 2005 (from $11B to$28B) the number of competing R01sawarded increased by only 46 (4959in 1996 to 7255 in 2004) there wereonly 6275 competing awards made in2005 The budgets of R01s increasedby 692 (average $ per R0129$2122k to $3589) during this sametime frame The investigator-initiatedR01s [that is those not solicited byprogram announcements (PA) orrequests for applications (RFA)] madeup 89 of the total in 1996 but by2003 they were only 83 and in

T

ASBMBToday DECEMBER 20062

2004 they dropped to 81 Thusunfortunately the NIH is driving moreand more of the research to thoseareas that the NIH itself decides areappropriate for funding

A new process that we have beenwatching carefully is the switch to elec-tronic submission of NIH proposalsStarting in February all R01 grantsmust be submitted electronically Weat ASBMB were alarmed to discoverthis past September that all investigatorswill need to choose a program announce-ment or RFA to respond to and there willno longer be a category for investigator-ini-tiated research

In the past the default pathway for anew application was investigator-initi-ated and one had to specifically stateif it was in response to an NIH-solicita-tion by including the PA or RFA num-ber Now one MUST submit a PAnumber for any application

Since that discovery we have beenworking hard with Norka Ruiz Bravothe Director of the Office of Extra-mural Research (OER) and NIH DeputyDirector for Extramural Research toconvince her that investigator-initiatedresearch is the bedrock of discoveryresearch and to change the system sofundamentally to remove this categoryis a grave error Although she agreedwith us that the lack of such a categorywas an oversight by the NIH unfortu-nately she was unable to change theprocess to add this category while theelectronic submission procedures werebeing developed for the web Weworked hard to convince her that theprocess needed to be significantlymodified to work around this problemand now they have indeed changed

N I H Responds to AS BM B Request

ASBMB Todayis a monthly publication

of The American Society for Biochemistry and Molecular Biology

OfficersHeidi E Hamm PresidentJudith S Bond Past-PresidentPeggy J Farnham SecretaryMerle Olson Treasurer

Council MembersJoan W Conaway CouncilorRobert A Copeland CouncilorKuan-Teh Jeang CouncilorJohn D Scott CouncilorWilliam S Sly CouncilorKevin Struhl CouncilorSuzanne Pfeffer CouncilorLinda Pike Councilor

Ex-Officio MembersJ Ellis BellChair Education and Professional DevelopmentCommitteeLaurie S KaguniChair Meetings CommitteeGeorge HillChair Minority Affairs CommitteeBenjamin F CravattMichael Rosen Co-chairs 2007 Program CommitteeWilliam R BrinkleyChair Public Affairs Advisory CommitteeRalph A BradshawDeputy Chair Public Affairs Advisory Commit-teeShelagh Ferguson-MillerChair Publications CommitteeHerbert TaborEditor JBCRalph A BradshawAl BurlingameCo-Editors MCPEdward A DennisEditor JLR

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

ASBMB Today9650 Rockville Pike Bethesda MD 20814-3996Phone 301-634-7145 Fax 301-634-7369

John Thompson jthompsonasbmborgEditor

Nicole Kresge nkresgeasbmborgScience Editor

Nancy J Rodnan nrodnanasbmborgDirector of Publications

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

ext 7157 or 301-634-7157 or email adnetfaseborg

From the Desk of the Pres ident

the wording on the NIH website to add PA numbers thatallow investigator-initiated research to be submitted

The following wording was added ldquoAn important proce-dural change with electronic submission of grant applica-tions is that all applications must be submitted in responseto a Funding Opportunity Announcement (FOA) NIH andother HHS Agencies plan to develop omnibus Parentannouncements by early November 2006 for our mostwidely used grant mechanism the research project grant(the R01) for use by applicants who wish to submit whatwere formerly termed ldquounsolicitedrdquo applications Respond-ing to such an omnibus or umbrella Parent FOA ensures thatthe correct application package is used and enables NIH toreceive the application from Grantsgov This process in no

way diminishes the interest of NIH Institutes and Centers ininvestigator-initiated unsolicited research grant applica-tions Parent announcements are NIH-wide but some NIHinstitutes may limit their participation so check theannouncements statement of interestrdquo

Now when you go to the NIH Grants and FundingOpportunities website and then to the OER home page andthen to the Funding Opportunities and Notices web pagescroll down to ldquoBrowse Active Funding Opportunitiesrdquo andyou will find ldquoParent Announcements (unsolicited applica-tions)rdquo There you will find the Parent R01 with theannouncement number PA-07-070 This announcementnumber can be used to download the electronic forms fromgrantsgov However beware that going to grantsgov andsearching with the keyword search for Parent Announce-ments investigator-initiated R01 or such words nets you621 opportunities It is a daunting task to delve through allof these To avoid this situation you must put thisannouncement number into the ldquoSearch by Funding Oppor-tunity Numberrdquo and it will be the only PA that is found

To help you to navigate this process there is a new issue ofNIH Extramural Nexus a special edition dedicated to theupcoming R01 electronic submission in February 2007(httpgrantsnihgovgrantspartners1106Nexushtm)

The mechanics of the electronic submission is quite differ-ent from the previous paper form and will certainly takelonger than usual at least the first time you do it The firstthing you will need to do to download an electronic form isto respond to a Funding Opportunity Announcement orFOA Please donrsquot wait to the last minute Hopefully theResearch Office (Sponsored Programs or Grants Manage-ment) at your University will be informed and capable ofhelping you in navigating the electronic submission processYou may wish to contact them now to determine if they areprepared for this new mechanism of NIH submission

There is ample documentation of this on the NIH websiteas well as on ASBMBrsquos public affairs web page

DECEMBER 2006 ASBMBToday 3

Dr Heidi E HammASBMB PresidentKeeps Door Open to Invest igator- Init iated Research

April 28 ndash May 2 2007 Washington DC

(Held in conjunction with EB 2007)

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


sional Biomedical Research Caucus)The new Majority Whip is Rep StenyHoyer (D-MD) a longtime member ofthe House LaborHHS AppropriationsSubcommittee

The new chairman of the LHHSSubcommittee will probably be RepDave Obey (D-WI) another House vet-eran with years of experience in appro-priations (he will also probably serve aschair of the full Appropriations Com-mittee) The committee will have a lotof work to do in January the outgoingGOP majority will not pass the 10remaining appropriations bills beforethe new Congress convenes thus giv-ing the Democrats $460 billion inunpassed bills to deal with as soon asthe new Congress reconvenes

The new chairman of the Energyand Commerce Committee (whichoversees NIH) will be Rep John Din-gell (D-MI) who during the 80s and90s presided over numerous investiga-tions of issues associated with biomed-

ical research including excessive uni-versity indirect cost charges and mis-conduct in science

Regarding the NIH reauthorizationbill The outgoing chairman of thecommittee Rep Joe Barton (R-TX) pro-duced a bill that many in the biomed-ical community endorsed (includingASBMB and FASEB) Democratsendorsed the Barton bill overwhelm-ingly (it passed the House in Septem-ber with only a handful of ldquonordquo votes)but several changes in a new versionare likely next year

Rep Henry Waxman (D-CA) willprobably chair the House GovernmentOperations Committee and he can beexpected to vigorously pursue a widerange of investigations of supposedBush administration malfeasance Forexample he is one of the few Membersof Congress to publicly decry ldquopoliti-cization of sciencerdquo in areas such asglobal warming reproductive healthand stem cell policy

robably betterrdquo is how one long-time congressionalobserver characterized the

outlook for science in the next Con-gress which will be controlled bythe Democrats for the first time in12 years as the result of the Novem-ber 7 election

The Democratic majority in theHouse is 29 seats as of this writingwith five races still undecided Theelection sent a clear message not oneincumbent House Democrat runningfor reelection was defeated

Iraq was the single largest issueworking against the GOP PresidentBushrsquos unpopularity was also a factorVarious scandals figured in a halfdozen other House races

Republicans who suffered mosttended to be moderates in the north-east and the Midwest many of whomwere staunch supporters of science andbiomedical research Typical was thedefeat of Rep Jim Leach (R-IA) a long-time GOP maverick very much at oddswith the conservative wing of theRepublican Party for most of his careerLeach lost narrowly to a Democratwho portrayed him as an ldquoenablerrdquo ofunpopular White House policies Veryfew Republican congressmen nowremain in all of New England and theseats that flipped will be difficult forthe GOP to reclaim in future elections

New LeadersmdashNewApproaches

The presumptive new Speaker of theHouse is Rep Nancy Pelosi (D-CA) thefirst female Speaker in history (she isalso a former co-chair of the Congres-

Democrats Take Over Congress OutlookldquoP

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

Members of the ASBMB Public Affairs Advisory Committee met with outgoing Rep SherwoodBoehlert (R-NY) long-time chair of the House Science Committee on November 14 to present himwith the Societys Howard K Schachman Public Service Award From left to right Robert Wells

Executive Director Barbara Gordon Boehlert Judith Bond and Thomas Smith


keeping Independent (and newlyreelected) Senator Joe Lieberman (I-CT)happy enough to continue to caucuswith the Democrats If he were todecide to become a Republican orbegin to caucus with them the GOPwould regain control of the Senate in a50-50 split with Vice President Cheneycasting any needed tie-breaking vote

Several strong opponents of stem cellresearch were defeated including Sena-tors Rick Santorum (R-PA) and Jim Tal-ent (R-MO) Talentrsquos narrow defeat hasbeen tied to the passage of a pro-stemcell ballot initiative (that ASBMB sup-

ported) Talentrsquos opponent supportedthe initiative However there is still nota veto-proof majority for any pro-stemcell legislationmdashwhich the Presidentwould undoubtedly vetomdashthat mightemerge from the next Congress

The chairmanship of the LHHSsubcommittee will switch to SenatorTom Harkin (D-IA) from SenatorArlen Specter (R-PA) but this does notrepresent much of a change as far asNIH is concerned since the two sena-tors have both supported NIH formany years and enjoy a close workingrelationship

The outlook for the treatment of sci-ence in the House is perhaps better inthe next couple of years than it hasbeen but it remains to be seen if thenew majority will assign a high prior-ity to funding it Competition forscarce Federal funds will likely be evenmore intense than it has been in thelast couple of years

On to the Senate The Democrats managed to wrest

control of the Senate from the GOP aswell although with a slim 51-49majority Democratic control rests on

for Science ldquoProbably Be tterrdquo


F A S E B W A S H I N G T O N U P D A T E F A S E B W A S H I N G T O N U P D A T E

synthetic genomics NSABB has beenactively seeking engagement with thebroader scientific community onthese issues setting up meetings withstakeholders and participating indomestic and international scientificand professional conferences Theirmeetings are open to the public web-cast live and all meeting materialsand agenda items are available onlineat the NSABB website wwwbiosecuri-tyboardgov

Among the NSABB draft productscurrently available for viewing on theirwebsite are the criteria for identifyingdual use research and evaluatingwhether it is of concern and in need offurther review This review process isthe subject of the NSABB workinggroup on oversight which is develop-ing an oversight and review frameworksimilar to that of IACUCs IRBs or theRAC In addition NSABB has pub-lished considerations for developing acode of conduct for life sciences whichthey see as a guideline for use by scien-tific societies or institutions The syn-thetic genomics group has just issued areport recommending potential modi-fications to the select agents rules aswell as proposed restrictions or regula-tions on suppliers of synthetic DNADirected at both publishers and scien-tists the communications workinggroup has put forward several productsand reports related to publishingresearch with dual use implicationsAmong NSABBrsquos charges as a federaladvisory body is to serve as a nationallevel of review and advice for the dis-semination of research results Theirfirst foray into this function was thereview of the publication of the recon-

structed 1918 influenza virus in Sep-tember 2005

Why should biomedical researcherspay attention to NSABBrsquos activitiesNIH has made it very clear that whenNSABBrsquos products and recommenda-tions are final they plan to imple-ment many of them as requisite forfederal funding Given the intera-gency nature of NSABB it may belikely other federal science agencieswill follow suit For example the syn-thetic genomics working group hassuggested a number of ways suppliersof synthetic DNA might prevent aid-ing the construction or reconstruc-tion of a pathogenic organismincluding referencing the selectagents taxonomy and keepingdetailed records They have also rec-ommended that federal grantees berequired to obtain synthetic DNAonly from those suppliers complyingwith these rules Although many ofthe NSABBrsquos recommendations arethoughtful proactive and evensound policy it is without doubt thatif implemented they will affect lifescientists FASEB has been followingthe activities of NSABB very closelyand in June FASEB President LeoFurcht MD participated in a round-table discussion to provide input onNSABBrsquos criteria for identifying dualuse research NSABB plans on pub-lishing all of its recommendationsand products when final in the fed-eral register for public comment Inthe meantime however nearly all oftheir documents are freely availableonline for review and members ofNSABB seem eager to receive feed-back from the scientific community

The National Science AdvisoryBoard on Biosecurity (NSABB) isbeginning to generate and shareproducts that could ultimatelyimpact federally funded scientistsNSABB was formed in early 2005 todevelop federal regulations andreview processes related to dual usebiological research The term lsquodualusersquo refers to research whose purposeis benign or beneficial but whosemisuse could cause harm Concernabout dual use research was raisedfollowing a 2004 report by theNational Academies titled Biotech-nology Research in an Age of Terror-ism Confronting the Dual UseDilemma Officially administeredthrough the National Institutes ofHealthrsquos (NIH) Office of Biotechnol-ogy Activities NSABB comprises 25voting members with expertise in sci-ence biosecurity biodefense phar-maceuticals and or law as well as18 ex-officio members representingvarious federal departments andagencies

Over the course of the past twoyears NSABB has been meeting bian-nually and conducting its work pri-marily through working groups Thegroups have been developing criteriafor identifying and evaluating dualuse research generating communica-tion strategies related to dual useresearch exploring the use of codesof conduct for life sciences andbeginning to outline a regulatoryscheme for control of dual useresearch More recent working groupprojects include outreach to theinternational research and policycommunity and the regulation of

Biosecurity Board Recommendat ionsMay Affect Future Biomedical Research

By Carr ie D Wo l i netz Ph D FASEB O f fice of Pub l i c A f fa i rs


The projects areKelly Kelleher MD of the Colum-

bus Childrenrsquos Hospital and the OhioState University and Joel GreenhousePhD of Carnegie Mellon Universitywill build on data initially collected bythe FDA to analyze antidepressantmedication use and suicidal behavioramong youth adults and older adultsKelleher will use new and more sensi-tive statistical approaches to integratedata from numerous other studiesmdashboth randomized and non-experimen-talmdashto paint a more complete pictureof the relationship between antidepres-sant medication use and suicidalthoughts or actions

Marcia Valenstein MD of the Uni-versity of Michigan will examine therecords of 994000 individuals fromthe US Department of Veterans AffairsNational Registry for DepressionMedicare records and the NationalDeath Index to determine what rela-tionships exist between the use of anti-depressants and suicide attemptsandor deaths and the use of any con-current medications or treatments Thestudy will help determine the relativeeffectiveness of different depressiontreatments in reducing suicidalthoughts and actions

Wayne Goodman MD of the Uni-versity of Florida will investigate if andhow SSRIs may induce in some youngpeople an ldquoactivation syndromerdquomdashaset of symptoms such as irritability agi-tation and mood swings that may leadto suicidal thoughts or actions He willstudy this potential syndrome amongpediatric patients diagnosed withobsessive compulsive disorder Byfocusing on patients with a disorderthat is less likely to be associated with

suicidality he will be able to betterassess whether SSRIs are related to anactual activation syndrome andwhether suicidality is a component ofthe syndrome The study will improverecognition and understanding of thesyndrome and help identify interven-tions that will reduce the risk of suicide

Sebastian Schneeweiss MD ofBrigham and Womenrsquos Hospital willassess critical issues surrounding thesafety of antidepressant medicationuse by comparing several large datasetsof SSRI users He will measure rates ofsuicidality identify social and demo-graphic factors that may be associatedwith SSRI use and suicidality andexamine the impact of FDA actions onuse of SSRIs The study aims to developand better target prescribing and riskmanagement strategies

Prudence Winslow Fisher PhD ofthe New York State Psychiatric Insti-tute will develop better and more reli-able ways of monitoring for adversereactions to the use of antidepressantmedication The studyrsquos long term goalis to construct a standardized com-puter tool for adolescents and parentsthat could be used to screen for suici-dality associated with the use of anti-depressant medications

In addition to these new projectsNIMH is funding other studies thataim to find the best treatments forindividuals suffering from depressionand reduce or prevent suicidal behav-ior Studies focused on youth depres-sion and suicidal behavior include theTreatment for Adolescents withDepression study the Treatment ofSSRI-Resistant Depression in Adoles-cents and the Treatment of AdolescentSuicide Attempters

he National Institute ofMental Health (NIMH) partof the National Institutes of

Health (NIH) is funding five newresearch projects that will shed lighton antidepressant medicationsnotably selective serotonin reuptakeinhibitors (SSRIs) and their associa-tion with suicidal thoughts and actions

Studies have shown that most indi-viduals suffering from moderate andsevere depression even those with sui-cidal thoughts can substantially bene-fit from antidepressant medicationtreatment However use of SSRIs inchildren and adolescents has becomecontroversial In 2005 the US Foodand Drug Administration (FDA)adopted a ldquoblack boxrdquo warning themost serious type of warning in pre-scription drug labeling for all SSRIsThe notice alerts doctors and patientsof the potential for SSRIs to promptsuicidal thinking in children and ado-lescents and urges diligent clinicalmonitoring of individuals of all agestaking the medications This can beparticularly challenging because it isdifficult for patients their familymembers and practitioners to deter-mine whether suicidal thoughts maybe related to the depression the med-ication or both

ldquoThese new multi-year projectswill clarify the connection betweenSSRI use and suicidalityrdquo said NIMHdirector Thomas Insel ldquoThey willhelp determine why and how SSRIsmay trigger suicidal thinking andbehavior in some people but notothers and may lead to new toolsthat will help us screen for thosewho are most vulnerablerdquo

T

N I M H Research Seeks to Find How

Ant idepressants May Be Associated with Suicide

N I H N E W S



are heterozygous with only one defec-tive allele produce about half the nor-mal level of frataxin but do not sufferdisease symptoms This suggests that atreatment for Friedreichrsquos ataxia neednot raise frataxin production all theway to normal levels to be effective

Joel Gottesfeld PhD a professor inthe Scripps Research Department ofMolecular Biology and leader of the pro-ject notes that the repeats causingFriedreichrsquos ataxia are in a region of thegene that does not code for the proteinfrataxin so reversing gene silencing maybe all that is needed to treat the disease

Researchers are still working to under-stand the reasons the triplet repeats pre-vent transcription of the frataxin geneOne idea suggested by the paperrsquosauthors is that the triplets cause anunusual DNA structure that attracts pro-teins such as histone deacetylases(HDACs) removing critical acetylgroups from the histones packaging thehistones in an inactive form called hete-rochromatin and ultimately leading tosilencing of the frataxin gene

Based on this theory Gottesfeld andhis colleagues began looking for com-pounds that might block the HDACswith the goal of reactivating frataxinproduction The researchers were ableto draw from a range of commerciallyavailable products because manyHDAC inhibitors have been developedas tools for molecular biology researchand as potential cancer treatments

Experiments revealed that oneHDAC inhibitor called BML-210 didin fact reverse the heterochromatinformation in cultured lymphocytesfrom Friedreichrsquos ataxia patients andincreased the production of frataxinmessenger RNA (mRNA) although notsufficiently to bring protein produc-tion to normal

Next the researchers chemicallymodified BML-210 to produce a varietyof analogs whose effects on the cellswere then tested One class of analogsproduced a two- to three-fold increasein frataxin transcription amounting tofull reactivation of the frataxin gene in

n a study published in theOctober issue of NatureChemical Biology researchers

tested a variety of compounds thatinhibited a class of enzymes known ashistone deacetylases in a cell linederived from blood cells from aFriedreichrsquos ataxia sufferer One ofthese inhibitors had the effect of reac-tivating the frataxin gene which issilenced in those with the disease

The researchers then went on toimprove on this molecule by synthesisof novel derivatives identifying com-pounds that would reactivate thefrataxin gene in blood cells taken from13 Friedreichrsquos ataxia patients In factone of the compounds the researcherstested produced what amounted to fullreactivation of the frataxin gene in 100percent of cells tested

About one of every 20000 to 50000people in the United States has Friedre-ichrsquos ataxia which is caused by a geneticdefect that prevents adequate produc-tion of the protein frataxin In neuronaland muscle cells frataxin is essential forproper functioning of mitochondriaLow levels of the protein lead to degen-eration of nerve tissue in the spinal cordand nerves controlling muscle move-ment in the arms and legs

The genetic defect involves numer-ous extra repeats of a GAA-TTC tripletpattern in a personrsquos DNA that pre-vent expression of the frataxin geneWhere normal cells contain 6 to 34repeats Friedreichrsquos ataxia suffererscan have as many as 1700 The moretriplets a personrsquos DNA contains theearlier symptoms appear and thegreater their severity

Only individuals who carry theFriedreichrsquos ataxia defect on both oftheir paired alleles ie who arehomozygous for the trait suffer fromthe condition Those individuals who

Scient ists Reverse Friedreichrsquos AtaxiaDefect in Cell CultureI ASBMB member Joel M

Gottesfeld is Professor in theDepartment of Molecular Biol-ogy at The Scripps ResearchInstitute in La Jolla CaliforniaHe received his BA in Bio-chemistry from the Universityof California Berkeley in1971 and his MSc in Bio-chemistry from Merton CollegeOxford University in 1973 He thenearned his PhD in Biochemistry fromthe California Institute of Technologyin 1975 Gottesfeld joined the Divisionof Cellular Biology at The ScrippsResearch Institute as an Assistant Mem-ber in 1978 He then became a memberof the Department of Molecular Biol-ogy in 1984 Gottesfeld left Scripps in

1989 to become Chief of theDivision of DevelopmentalBiology at the Medical BiologyInstitute in La Jolla butreturned to the Scripps in 1992 Research in the Gottesfeld lab-oratory concerns the protein-DNA interactions involved inregulation of gene expression

in mammalian cells and the develop-ment of small molecules to regulategene expression at will His currentresearch focuses on the developmentof Py-Im polyamides as new therapeu-tics for human diseases includingcancer neurodegenerative diseasesand infectious diseases Gottesfeld isalso an Associate Editor for the Journalof Biological Chemistry

Dr Joel M Gottesfeld

Continued on next page


to TFII-I The fish-ing expeditionreturned one pro-tein known to con-trol when and howmuch calcium acell takes in

ldquoThe partner wefound in the fish-ing experimentand the abundanceof TFII-I outside thecell nucleus led us to suspect that thisprotein must be doing more than regu-lating gene expressionrdquo says Desiderio

ldquoThe finding was stunning to usbecause calcium is one of the mostimportant messengers in cellsrdquo saysDesiderio ldquoand both it and TFII-I are inevery cell That affirmed our suspicionthat TFII-I could be doing somethingimportant with calcium signalingrdquo

In one experiment the Hopkinsteam knocked down the amount ofTFII-I in lab-grown cells and looked forchanges in calcium flow under a high

ohns Hopkins researchers haveteased out the function of aprotein implicated in Williams-

Beuren syndrome a rare cognitive disor-der associated with overly social behaviorand lack of spatial awareness Called TFII-I the protein which has long beenknown to help control a cellrsquos genes alsocontrols how much calcium a cell takesin The study was published in the Octo-ber 6 issue of Science

ldquoWhile the previously described func-tion of TFII-I very well also could con-tribute to the cognitive defects ofWilliams-Beuren syndrome its role con-trolling calcium makes much moresenserdquo says Stephen Desiderio MDPhD a professor of molecular biologyand genetics and director of the Insti-tute of Basic Biomedical Sciences atHopkins And says Desiderio othershave shown that defects in a cellrsquos abil-ity to take in calcium can lead to otherneurological and behavioral conditions

Williams-Beuren syndrome occursin roughly one in 25000 births and iscaused by a deletion of a small sectionof chromosome 7 that contains sev-eral genes including the gene thatencodes the TFII-I protein

The discovery came after Desiderioand his team used biochemical bait tofish for candidate proteins that bind

J

Researchers Uncover Cri t ical Player inCell Communicat ion

an astonishing 100 percent of cellsfrom 13 Friedreichrsquos ataxia sufferers

Importantly the teamrsquos HDACinhibitors have also proven uniformlynon-toxic to the lymphocytes and donot significantly affect cell growthrates Ongoing animal studies alsohave not revealed any toxicity If theresults of animal testing remain posi-tive said Gottesfeld the HDACinhibitors could enter human trials asa Friedreichrsquos ataxia treatment in assoon as 18 monthsrsquo time

power microscope using a dye thatglows when it comes in contact withcalcium The researchers realized thatwhen they depleted the cells of TFII-Ithe cell responded by installing morecalcium channels on their surfaces

ldquoTherersquos good evidence suggestingthat the frequency and intensity ofthis ebb and flow of calcium can deter-mine a cellrsquos response to externalcuesrdquo says Desiderio ldquoTFII-I may be auniversal player in communicationbetween cells in the brain theimmune system and elsewhererdquo

PHCPHN

PHCPHN 2 2 3PLC

PHNTRPC3

PHCPHN 2 2 3

PHCPHN

P

PHN

TFII-Ikinase

phospholipid

F

A model for antagonism between PLC-gamma and TFII-I in which TFII-Ifluctuates between ldquoopenrdquo and ldquoclosedrdquo states

ASBMB member Stephen Desiderio isDirector of the Johns Hopkins Institutefor Basic Biomedical Sciences (IBBS) Hereceived his BA from Haverford Col-lege in 1974 and completed his MDand PhD degrees at the Johns HopkinsUniversity School of Medicine in 1981He joined the faculty of the Johns Hop-kins University School of Medicine in1984 and became a Howard HughesMedical Institute Investigator in 2000He became Director of the Program inImmunology of the Johns HopkinsInstitute for Cell Engineering in 2002and was named Director of IBBS in 2003

Desiderio is the recipient of numer-ous awards and honors including the1993 Professorsrsquo Award for Excellence

in Teaching fromthe Johns Hop-kins UniversitySchool of Medi-cine and theMichael AShanoff ResearchAward He hasauthored or co-authored works in more than 54 pub-lications He currently studies theimmune system and mechanismsthat govern assembly of antigenreceptor genes His laboratory hasbegun to use new tools of geneticsand genomics to describe and dissectimmune responses that are geneti-cally hardwired or stereotypic suchas the onset of inflammation

Dr Stephen Desiderio


halves joined by a hinge at one endand held closed most of the time by alatch of hydrogen bonds on the otherend When the bowls come togetherlike a shut mouth they enclose achamber shaped like a triangularprism with a base that measures 35 x34 x 30 angstroms and a height of 36angstroms large enough to containrelatively small peptides such asinsulin or amyloid-beta which havefewer than 50 amino acids

Although it can cleave larger mole-cules the proteins IDE degrades mostreadily fit neatly within this chamberNegative electrical charges on their outersurfaces help to align them with the pos-itive charges on one inner surface of thechamber Once they are in place theenzyme slices them multiple times intotiny pieces which are then discarded

Although the enzymersquos structure issimilar to Pac-Man its behavior differsPac-Man keeps his mouth wide opento gobble up anything in his pathWith IDE the mouth is usually closedThe hydrogen bond latch that holdsthe jaws together protects its active orcatalytic site

But in a series of experiments Tangand colleagues were able to make smallmutations of IDE that altered only thelatch disrupting the alignment of con-tacts that normally keep the enzymeclosed Three of these altered versionsof wide open IDE proved to be 30 to 40

esearchers from the Univer-sity of Chicago and ArgonneNational Laboratory have

deciphered the three-dimensionalstructure of insulin-degrading enzymea promising target for new drugsbecause it breaks down not onlyinsulin but also the amyloid-beta pro-tein which has been linked to the cog-nitive decline of Alzheimer disease

In the October 19 issue of Nature theresearchers described the structures ofinsulin-degrading enzyme (IDE) incomplex with four of the proteins itdigests insulin amyloid-beta amylinand glucagon The structures suggestways to develop drugs that couldeither speed up or slow down thisubiquitous enzymersquos activity

ldquoThe structure of insulin-degradingenzyme tells us a lot about how itworks which is somewhat unortho-doxrdquo said Wei-Jen Tang PhD associ-ate professor in the Ben May Institutefor Cancer Research at the Universityof Chicago and director of the studyldquoUnderstanding how it works gives usclues about how to design drugs eitherto inhibit or activate it

ldquoBy introducing small targetedmutations we have already been ableto increase the enzymersquos activity by asmuch as 40-foldrdquo he said ldquoThat givesus a blueprint for the next step tryingto devise a drug that would produce asimilar effectrdquo

Using the Advanced Photon Source atArgonne National Laboratory Tang andcolleagues were able to solve the struc-tures of this enzyme in complex withinsulin and with amyloid-beta as well asamylin and glucagon These high resolu-tion crystal structures open the door tothe rational design of pharmacologicalmodulators of this important protease

The enzyme Tangrsquos team reportsresembles the video game characterldquoPac-Manrdquo with two bowl-shaped

Structure of Enzyme Offers TreatmentClues for Diabe tes AlzheimersR

IDE resembles the video gamecharacter ldquoPac-Manrdquo with twobowl-shaped halves joined by a

hinge at one end and heldclosed most of the time by a

latch of hydrogen bonds on the other end

ASBMB member Wei-JenTang is an Associate Professorat the Ben May Institute forCancer Research at the Univer-sity of Chicago He receivedhis BS in Zoology at theNational Taiwan University in1982 After two years of servicein the Republic of Chinarsquos AirForce his earned his PhD in Biologi-cal Sciences at the University of Texasat Austin in 1988 He became anInstructor at the University of TexasSouthwestern Medical School in 1991and was promoted to Assistant Profes-sor in 1993 He joined the faculty ofthe University of Chicago in 1994

Tang has authored or co-authored works in more than50 publications and holdstwo patents He is the recipi-ent of many honors andawards including the 1999American Heart AssociationEstablished InvestigatorAward His laboratory cur-

rently focuses on elucidating themolecular basis of cell communica-tion by analyzing the interactionbetween prokaryotic and eukaryoticcells His current research deals withthe biology of bacterial adenylylcyclase toxins proteins that secretedby human bacterial pathogens

Dr Wei-Jen Tang

Structure of human insulin-degrading enzyme(IDE) in complex with beta-amyloid



senior author of a report on this workthat appears in the October issue ofJournal of Proteome Research

ldquoUntil now there was no way to sep-arate IUPs in large numbers from themore structured proteins and confirmtheir roles in the cellrdquo Kriwacki saidldquoOur new technique selectively con-centrates the IUPs that are involved inregulating functions in the cell andtransmitting signals within themrdquo

Unlike the classic description of pro-teins described in science textbooksIUPs are not completely locked intorigid three-dimensional shapes thatdetermine their function in the cellInstead IUPs have varying amounts offlexibility within their sometimesspaghetti-like structures that is criticalfor function For example one proteinnamed p27 initially looks like aSlinkyTM toy However when p27goes to work it puts a vise-like grip onan enzyme that otherwise would pro-mote uncontrolled cell division

The St Jude team developed a tech-nique that uses heat to isolate IUPs inlarge purified quantities from extracts ofNIH3T3 fibroblasts The IUPs were resis-tant to the heat unlike more structuredproteins which fell apart Based onthese studies the investigators were ableto classify all proteins into one of threecategories IUPs intrinsically folded pro-teins (IFPs ie fully folded into specificshapes) or mixed ordered or disorderedproteins (MPs) which have both struc-tured and unstructured parts

ldquoThis work further illustrates thatthe disorderliness of IUPs isnrsquot just acuriosityrdquo said Charles Galea PhD apostdoctoral fellow in Kriwackirsquos labldquoThis characteristic is a fundamentalpart of how these proteins work Sodetermining their exact nature includ-ing the parts that are disordered is animportant part of understanding howthey work This is especially importantin the case of IUPs linked to cancerand other diseasesrdquo

nvestigators at St Jude Chil-drenrsquos Research Hospitalturned up the heat on ldquodisor-

derlyrdquo proteins and confirmed thatmost of these unruly molecules per-form critical functions in the cell TheSt Jude team completed the first largescale collection investigation andclassification of these so-called intrinsi-cally unstructured proteins (IUPs) alarge group of molecules that play vitalroles in the daily activities of cells

The new technique for collectingand identifying IUPs is importantbecause although scientists have beenaware of the existence of flexible pro-teins for many years they have onlyrecently realized that these moleculesplay major biological roles in the cellaccording to Richard Kriwacki PhDan associate member of the St JudeDepartment of Structural BiologyMoreover he said previous work byother researchers suggested that a largeproportion of IUPs in mammalian cellsplay key roles in transmitting signalsand coordinating biochemical andgenetic activities that keep the cellalive and functioning Kriwacki is

I

First Major Study of MammalianldquoDisorderlyrdquo Proteins

IUPs play diverse roles in cells by folding upon binding to their regulatory targets

ASBMB mem-ber Richard Kri-wacki PhD isan assistantmember in theSt Jude Chil-drenrsquos ResearchHospital Struc-tural BiologyDepartment Hejoined the St Jude staff in 1997after performing postdoctoral stud-ies at The Scripps Research Instituteand receiving graduate training atYale University

Kriwackirsquos laboratory applies struc-tural biophysical and cell biologytechniques to understand the rela-tionships between protein structureand biological function Emphasis isplaced on studies of proteins withintumor suppressor pathways espe-cially those involved in regulatingthe cell division cycle because theirgenes are frequently targeted bymutations in cancer

Dr Richard Kriwackitimes more active than the normal ver-sion of the enzyme

ldquoThis suggests that the rate limitingstep may be the speed at which theenzyme can reopen and then clampdown on a new morsel rather than thetime it takes to chew something uprdquosaid Tang ldquoThis makes us think that ifwe can slightly alter its shape we cansubstantially boost its activityrdquo

The researchers are now searching forsmall molecules that can duplicate theeffects of those mutations shifting thebalance toward the open rather than theclosed state ldquoSuch compoundsrdquo theauthors note ldquomight facilitate the clear-ance of amyloid-beta and other patho-logically relevant IDE substratesrdquo


Trans it ion ing fromAcademic toIndustr ia l Sc ience

Everyone who enters the biomedicalindustry comes out of an academic set-ting where there are specific goals andapproaches to how science is done Thegoals and approaches in industry aredistinct and can seem quite foreign tothe newcomer it is thus worthwhile toconsider how these two settings differ

One of the most obvious differencesis in the degree of focus that is appliedto biological questions within the twosettings While academic researcherstend to ask questions of broad interestthe industrial researcher must take amore practical view focusing attentionalmost exclusively on questions ofpathobiology that have a direct clinicalutility To exemplify this consider theactivity of target validation within thepharmaceutical industry The goal hereis to determine whether the activity of aparticular biomolecule (usually a pro-tein) is critical to a specific diseaseprocess and whether targeting this bio-molecule for drug intervention willhave the desired effect on the diseaseThis activity requires the combinedefforts of scientists from multiple disci-plines including biochemistry molecu-lar biology genetics cellular and animalbiology and perhaps medicinal chem-istry One can invest many months oreven years in understanding thedetailed role of a putative target in forexample cell signaling Along the wayone may uncover fascinating aspects ofthe cell biology associated with a partic-ular biomolecule but may also discoverthat it is not an appropriate target fordrug discovery At such a point an aca-demically trained scientist may betempted to explore further the interest-ing biochemistry and biology of themolecule to add to the general knowl-

edge base The industrial scientist how-ever must immediately abandon fur-ther work on such a target as toprolong efforts on the target would becounterproductive to the goal of bring-ing new medicines to patients in needThe industrial scientist is likely to pub-lish hisher finding so that others per-haps in academics can pursue the basicscience but would then quickly moveon to other activities This exampleillustrates another distinction betweenacademic and industrial research pro-ject lifetimes are much more finite inthe industrial setting It is not uncom-mon for an academic scientist to pursuea major research project or at least acommon research theme for a signifi-cant portion of their career In contrastprojects in industry are of more limitedduration defined either by successfultransition to the market or by suspen-sion for pragmatic reasons as justdescribed Pharmaceutical research isexpensive current estimates of the typi-cal cost of going from target identifica-tion to a marketed drug are in the rangeof 900 million US dollars Hence if aproject is not going to yield a usabledrug it is in the researcherrsquos and thecompanyrsquos best interest to discover thisand terminate the project as early aspossible For this reason scientists inindustry are often challenged to comeup with what are commonly referred toas ldquokiller experimentsrdquo - designed to testrigorously the suitability of a scientificapproach for progression Failure tomeet predetermined outcomes in suchexperiments would lead to termination(ie ldquokillingrdquo) of the project

For young investigators in academicsettings (eg assistant professors) thereis usually a strong incentive to work asan independent researcher and toavoid significant collaborative researchThis is because collaborative research

he desire to find practical solu-tions to problems of commer-cial interest has fueled key

discoveries in the biochemical sciencesfrom early civilizations to the presentThroughout history practical applica-tions of biological chemistry have con-tributed in myriad ways to improvingthe human condition In moderntimes industrial applications of bio-medical sciences perhaps most notablywithin the pharmaceutical industryhave contributed greatly to extendingand enhancing human life through thediscovery development and commer-cialization of medicines diagnosticsand medical devices

Hence innovation creativity and thedesire to apply these skills in a focusedand contemporaneous way to societalproblems has been and continues to bethe hallmarks of industrial biomedicalscience A scientific career in industrycan be extremely rewarding for thosewho wish to see the potential fruits oftheir labors translate into meaningfulimpact on humanity within their ownlifetime A growing number of young sci-entists are emerging from their academictraining with the realization that theirprofessional aspirations can be best metthrough a career in industry Althoughmany bright and talented students havecome to this realization few of themhave any familiarity with how science isconducted within an industrial settingand what skills are most valued by theirpotential employers This month andnext month I will attempt to addressthese issues in a two-part series on bio-medical careers in industry All of myindustrial experience has been in thepharmaceutical industry and I will focusmy comments on this industry I suspecthowever that many of the statements Iam about to make apply equally well toother biomedical industries as well

T

Biomedical Careers in Industry By Robert A Cope land Ph D V ice Pres ident Enzymo logy amp Mechan ist ic Pharmaco logy

G laxoSm i thK l i ne Pharmaceut ica ls


success in the industrial sector There isno generic answer to this type of ques-tion Every company and every individ-ual hiring manager will have differentperspectives on this issue I can onlyanswer this question from the perspec-tive of a supervisor and hiring managerin terms of what I personally find ofmost value in potential employeesBelow I describe some of the attributesthat I look for in job candidates

Be a scientist not a technologistEveryone coming out of their academictraining will have honed their skills inspecific types of technologies Employ-ers expect you to be a master of yourcraft However it is a fundamental mis-take to market yourself on the basis of acollection of specific techniques thatyou are trained in Rather what is mostvalued is someone who demonstratesgood scientific problem solving abili-ties This involves being able to iden-tify important scientific problemsdefine a cogent plan for experimentallyapproaching the problem collect andanalyze data appropriately testhypotheses objectively draw clear andthoughtful conclusions and be able toeffectively communicate these conclu-sions and their impact in the broadercontext of a drug discovery project tofellow scientists and laypeople

Demonstrate quantitative skillsWhile there are many important tech-niques in biological sciences that yieldqualitative results the greatest value isusually gained from quantitative dataHence researchers who can analyze andinterpret data in quantitative termsusing appropriate mathematical mod-els are highly sought after I believe thisto be universally true in all science butit is especially important to industrialscience Phenomenological observa-tions may be a good starting point foran investigation but it is only when

one can define a phenomenon quanti-tatively that one can truly begin tounderstand the nature of the observa-tions In the pharmaceutical industryquantitative data is needed at every stepin discovery and development Drug-target affinity cellular and in vivo dose-response analysis must all be expressedin quantitative terms synthetic stepsmust be quantified in terms of reactantstoichiometry and yields drug formula-tion must be precisely described andpharmacokinetics toxicokinetcs andpharmacodynamics must all be definedin a quantitative fashion

Communicate effectively I cannotstress enough the importance placedon effective oral and written commu-nication skills These are absolutelycritical to success in any field of sci-ence It doesnrsquot matter how brilliant atheoretician nor how skilled an exper-imentalist you are if you cannot com-municate your ideas results andconclusions to your peers and othersHence hone these skills throughoutyour academic training Write andspeak as often as you can Seek out andaccept constructive criticism frommentors colleagues and others whoseskills you admire If English is not yourfirst language donrsquot expect prospectiveemployers to take this into account itis up to you to be a competitive jobcandidate Therefore look for extrahelp during your academic training

Be a team player As Irsquove describedabove industrial science is a team sportPeople who can effectively network andcollaborate in the context of projectmatrix teams will be most successful inindustry Those who need all the gloryand therefore try to work in isolation aredoomed to failure in this setting Drugdiscovery is just too complicated for anyone person to master It is only through

projects make it difficult for tenurecommittees to assess the significance ofthe individual investigatorrsquos contribu-tions In stark contrast essentially allresearch in the industrial sector is doneas collaborative matrix teams This isnecessitated by the complexity of drugdiscovery requiring the concertedefforts of talented scientists from multi-ple disciplines from molecular biolo-gists and biochemists to cliniciansThus newcomers to the pharmaceuti-cal industry must adapt to this style ofinteractive and interdependent science

A final contrast between academic andindustrial science is the ultimate productof the efforts in these two sectors In aca-demics the ultimate product of researchis information most typically dissemi-nated in the form of scholarly publica-tions and lectures In industry theultimate product of research is a tangibleentity such as a new medicine in thecase of the pharmaceutical industryWhat about the information gleanedalong the path to product marketing Aswith our academic colleagues we indus-trial scientists share this informationwith the general scientific community inthe form of scholarly publications lec-tures and patents However where thesemedia for information sharing are thekey products of academic research theyare viewed as byproducts ndash importantbyproducts but byproducts nonetheless- of industrial research

Sk i l ls Va lued byIndustr ia l Emp loyers

As a young scientist nears completionof their academic training it is commonto begin thinking about how best topresent oneself to potential employersA question that frequently arises at thispoint is what are the skills and talentsthat are most valued by potentialemployers and that may portend career

A Few Tips for the Newcomer (Part 1)

Continued on page 15

SAVE THE DATE Apr i l 28 - May 2 2007 in Wash ington DC


versity of Wisconsin) will shed lightinto the energetics of an enzyme-cat-alyzed reaction Dr Dagmar Ringe(Brandeis University) will talk aboutthe mechanism of pyridoxal phos-phate one of the most universallyused cofactors in nature and howmechanism-based inhibitors for thisenzyme class function

Dr Peter Wright (The ScrippsResearch Institute) will chair the ses-sion The Role of Dynamics in EnzymeCatalysis and discuss dynamic NMRexperiments and classic enzymekinetics to describe the energy land-scape of the enzyme dihydofolatereductase (DFHR) Dr GordonHammes (Duke University) will fol-low with single molecule studies onDFHR Dr Dorothee Kern(HHMIBrandeis University) willexplore the dynamic personality ofenzymes by ldquowatchingrdquo them duringturnover Through combining crystal-lography NMR computation and sin-gle molecule FRET experiments sheinvestigates the hierarchy in timescale of dynamics Dr Judith Klinman(University of Berkeley) will presentexciting results on hydrogen tunnel-ing that give insight into the role ofdynamics in enzyme catalysis

The session on Computational Stud-ies of Mechanistic and DynamicalAspects of Enzyme Reactions chairedby Dr Sharon Hammes-Schiffer (Penn-sylvania State University) will empha-size the power of computation in ourefforts to understand how enzymesaccomplish their incredible catalyticefficiencies Dr Hammes-Schiffer willillustrate that by comparing computa-tional results on hydrogen tunnelingwith experimental data Dr KennethMerz (University of Florida) and Dr

Jiali Gao (University of Minnesota)will present a similar theme This ses-sion will demonstrate state of the artmethodology in computation and the strength of these methods ofdetecting correlated motions andcharacterizing pathways

The session on Enzyme Design willexemplify our current understandingof enzyme mechanism by rationaldesign of enzymes Stephen Mayo(HHMICalifornia Institute of Technol-ogy) will present recent successes incomputational enzyme design DrKendall N Houk (University of Califor-nia Los Angeles) will focus on theheart of an enzyme the active site Hewill show results from active sitedesigns based on Quantum Mechani-cal calculations Dr Homme WHellinga (Duke University MedicalCenter) will implement a number ofdifferent functions in a protein using acommon scaffold as a starting pointfor rational design

he enormous rate accelera-tion and specificity ofenzymes has fascinated sci-

entists for many decades While clas-sical enzymology has provideddetailed insight into the chemicalnature of these catalyzed reactionsstructural biology elevated our under-standing to a new level Recently therole of protein dynamics for enzymecatalysis has gained increasing inter-est New biophysical methods such asNMR spectroscopy single moleculeexperiments mass spectrometry aswell as development of sophisticatedcomputational approaches to thisproblem provide powerful tools toinvestigate this question The uniquefeatures of macromolecules to sampleconformational states a necessity forfunction is being presented in a sepa-rate but coordinated theme Macro-molecular Structure and Dynamics)

The Enzymes Theme at the 2007ASBMB meeting in Washington willoffer a comprehensive picture of ourcurrent understanding of enzymemechanisms based on all the abovementioned approaches Thanks to thediverse group of speakers we will seethe beauty of combining differentexperimental approaches and compu-tation to tackle the secrets of enzymesOpen questions will be identified thatneed to be addressed in the future

The session entitled StructuralEnzymology will highlight the incred-ible impact of x-ray crystallography tothe current understanding of enzymemechanisms Dr Karen Allen (BostonUniversity) will illustrate how knowl-edge of atomic resolution of a numberof intermediates in an enzymaticcycle reveals chemical details ofenzyme catalysis Dr Perry Frey (Uni-

T

AS BM B 2007 Enzymes Mechanism and DesignOrgan izer Dorothee Kern

Dr Dorothee Kern inserting an NMR sample ina 600 MHz NMR spectrometer

ASBMB Annual MeetingApr i l 28 - May 2 2007 in Wash ington DC


The second ses-sion Making andRe-Making DNAwas organized andwill be chaired byLorena Beese ofDuke UniversityMedical CenterLorena Beese willdiscuss insights into DNA replicationand repair Graham Walker of MIT willcover recent developments in under-standing the process of translesionDNA synthesis Greg Verdine willrecount the efforts of his lab to under-stand how DNA glycosyases locate raredamaged bases embedded in a vastexcess of undamaged DNA

The third session Telomeres andTelomerase was organized and will bechaired by Kathleen Collins of the Uni-versity of California Berkeley In this ses-sion Elizabeth Blackburn of theUniversity of California San Franciscowill talk about new developments instudies of telomeres and their mainte-nance mechanisms Kathy Collinsrsquo talkwill describe requirements for telomeraseribonucleoprotein assembly and activityin the cellular context Carol Greider willexplain their study regarding how shorttelomeres limit the division of both can-cer cells and stem cells and the role thatthis shortening plays in human disease

The fourth and final session Methylat-ing and De-methylating DNA was orga-nized and will be chaired by Tim Bestorof Columbia University College of Physi-cians and Surgeons In this sessionTomas Lindahl of Cancer Research UKwill discuss biochemical and cellular stud-

ies aimed at understanding human pro-teins responsible for the repair of aber-rantly methylated DNA Tim Bestor willtalk about methylation of aspartic acidtRNA by a protein that by sequence andstructure must be a DNA methyltrans-ferase Bob Fischer of the University ofCalifornia Berkeley will discuss how theDEMETER (DME) DNA glycosylase estab-lishes gene imprinting by demethylatingmaternal alleles in Arabidopsis

remendous strides have beenmade in recent years towardunderstanding what may be

called ldquothe secret life of the genomerdquothe spectacular enzyme-catalyzed oper-ations that alter the covalent structureof DNA to remodel its informationcontent and enable it to withstand thesometimes harsh environment of thecell Scientists at the leading edge ofthis revolution in our understandingof genomic husbandry will convene atthe 2007 ASBMB Meeting April 28 ndashMay 2 in Washington DC to providean account of their latest findings inthis fast-moving area This Themeorganized by Greg Verdine of HarvardUniversity and the Dana-Farber CancerInstitute and entitled From Genome toEpigenome ndash Modification and Repairconsists of four sessions each coveringan important topic in genome modification

The first session Recombining andModifying DNA was organized andwill be chaired by David Schatz of Yaleuniversity The talk of David Schatzwill focus on the use of FRET to exam-ine the structure of the synaptic com-plex formed by the RAG1RAG2proteins during V(D)J recombinationGreg Van Duyne of the HowardHughes Medical Institute and the Uni-versity of Pennsylvania School of Med-icine will discuss recent insights intothe asymmetric nature of the Cre-loxPsite-specific recombination reactionWilliam Reznikoff of the University ofMadison-Wisconsin will discuss struc-ture and function studies on transposi-tion catalyzed by Tn5 transposase

From Genome to Epigenome ndashModif icat ion and Repair

Organ izer Gregory Verd ine Harvard Un ivers i ty

T

Dr Greg Verdine

team efforts that new medicines can besuccessfully discovered and developed

Think holistically As a member of aproject matrix team you will have pri-mary responsibility for one aspect of theproject or for the application of one sci-entific discipline (eg biochemistry ormolecular biology) Again you areexpected to be a master of your specificdiscipline but that is not enough Suc-cessful researchers in the pharmaceuticalindustry are those who commit tounderstanding a project in its entiretyThis does not mean that one must be anexpert in every discipline Rather itmeans making a commitment to learn-ing enough about each aspect of a pro-ject team so that one can be an effectivecollaborator with onersquos colleagues fromdifferent disciplines and can best putonersquos own research in the correct con-text of the project team objectives

In part 2 of this series we will discusssome frequent misconceptions aboutindustry and some more generaladvice for career fulfillment

Careers cont inued hellipContinued from page 13



lished the first crystal structure of thecAMP-dependent protein kinase in1991 and there followed a highly pro-ductive period in which she illumi-nated the allosteric regulationdynamics catalytic mechanism andenergetics and recognition of sub-strates modifiers activators and otherbinding partner proteins

Taylorrsquos broad interests and collabora-tive style are evident in her activism inmaking the implications of her struc-tural insights as broadly available as pos-sible to the scientific community Sheworked hard with others in the field tocreate the Protein Kinase Resource(httppk[sdsceduhtmlindexshtml)which houses a rich compendium ofinformation about protein kinases andtools for structural and computationalanalyses Anyone who has beeninvolved in such broad community-minded endeavors knows that they arelabors of love and they require just theskills that Taylor has of imparting herenthusiasm and ambition to othersorganizing meetings and workinggroups and always passing along mostof the credit to her collaborators

Her interest in ways to foster wide-spread collaboration between disparatedisciplines that intersect around molecu-lar structure led to her active involve-ment in biomolecular computing incollaboration with the San Diego Super-computer Center where she is a SeniorFellow Taylor plays important leader-ship roles in biomolecular structuralvisualization and bioinformatics Shealso worked hard with Helen Berman on

a project that revolu-tionized the usabilityof the Protein DataBank (PDB) In herlocal environment inthe UCSD and SanDiego area she is abridge- builder con-sortium-builder andcollaborative force In addition she is asuperb recruiter for UCSD and the largerlocal scientific community

Taylor has played innumerablenational and international activistroles that are well-known to FASEB andits member societies She was an earlyadvocate for increasing involvement ofyoung people in scientific organiza-tions During her Presidency ofASBMB she spearheaded membershipdrives among young people andhelped to create the ASBMB Fall Sym-posia that showcased their talent Shehas worked tirelessly to advocate forincreased funding for science withFASEB and the Joint Steering Commit-tee (JSC) for Public Policy She excels atsearching out nurturing and mentor-ing young talent and has served onmany panels such as the David andLucile Packard Fellowships AdvisoryPanel the Burroughs Wellcome FundAdvisory Committee for Interfaces inScience Program (2004 Co-Chair) aswell as many others Not surprisinglyshe is a wonderful mentor to graduatestudents and postdoctoral fellowsmany of whom are by now accom-plished scientists holding academicpositions allover the world

ormer ASBMB PresidentSusan Taylor of the Depart-ment of Chemistry and Bio-

chemistry and an HHMI Investigatorat the University of California SanDiego has been selected to receive theWilliam C Rose Award The Award rec-ognizes outstanding contributions tobiochemical and molecular biologicalresearch and a demonstrated commit-ment to the training of younger scien-tists as epitomized by the late DrWilliam C Rose The Award consists ofa plaque stipend and transportationto the 2007 Meeting to present a lec-ture Recent recipients of this awardwere W L Smith in 2006 Frederick PGuengerich in 2005 Sunney IChanin 2004 Jack E Dixon in 2003and in 2002 Gordon Hammes

Taylor is one of the most preeminentscientists in the world studying thestructure and function of proteinkinases a large family of signaling pro-teins representing 2 of the humangenome and involved in many crucialcellular processes including growthmetabolism differentiation and apop-tosis Disregulation of this family ofmolecules underlies a number of dis-eases especially cancer Susan was thefirst to crystallize a protein kinase thecAMP-dependent protein kinasewhich revolutionized our understand-ing of the body plan of protein kinasesas a family This classic work has shedlight on the evolution function anddynamics of protein kinases She hasbeen for the past 20 years the leadingfigure this important field She pub-

F

Susan Taylor to ReceiveWill iam C Rose Award

Dr Susan Taylor



makes his research particularly freshand exciting Chris is now recognizedas a leader in his field of research andhis reputation will grow exponentiallyin the coming years

One nominator wrote ldquoBurge is arare commodity among computa-tional biologists in that he invariablycouples his analyses with experimen-tal tests of their validity Thus hisimportant conclusions have founda-tions in real biology and can beapplied with confidence by con-sumers of bioinformaticsrdquo I firstcame to admire Chrisrsquos approach dur-ing his postdoctoral work with PhilSharp His thorough analysis of thephylogenetic distribution of U12-type introns served as the basis forformulating a novel and I think rea-sonable hypothesis as to the originsof this unanticipated second class ofintrons and the spliceosome thatexcises them His 1997 Cell and 1998Molecular Cell papers proposed thatthe two spliceosomes evolved from acommon ancestor in separate lin-eages that later fused subsequentconversion over time of U12-typeintrons to the U2-type with moreflexible consensus sequences nicelyexplains the rarity and distribution ofsuch introns in the genes of modemmetazoans

Upon assuming a more independentposition (Bioinformatics Fellow) in1999 Chris extended hisanalyses ofthe behavior of introns to the mostchallenging question in pre-mRNAsplicing-how fidelity in splice sitechoice and pairing is achieved These

phenomena under-lie alternative splic-ing which we nowappreciate has mul-tiplied the func-tional potential ofthe 28000 genesestimated to com-prise the humangenome Burgersquos 2001 PNAS paperfound that ldquointron definitionrdquo worksslightly differently in different organ-isms and framed a picture of the mini-mal set of features being recognized -in each case Equally impressive washis 2002 Science paper that combinedcomputational prediction of exonicenhancer sequences with experimentalverification of their functioning Theinterested biologist was therefore notleft dangling in computational spacewaiting for someone else to test theconclusions

In his subsequent analyses of aher-natively spliced introns Burge hascoupled a clever in vivo reporter-basedscreen with computational approachesto identify decameric exonic splicingsilencers some of which correspondto known recognition sequences forabundant nuclear RNA-binding pro-teins Likewise exons conservedbetween mouse and man identifiedby an exon classification algorithmwere confirmed to exist in alterna-tively spliced transcripts by RT -PCRsequencing Interesting differencesbetween the use of alternative splicingin mouse and man have been uncov-ered and have evolved into useful data bases

r Christopher Burge of theDepartment of Biology atMassachusetts Institute of

Technology will receive the Schering-Plough Research Institute Award at theASSBMB Annual Meeting April 28 ndashMay 2 in Washington DC The Scher-ing-Plough Award recognizes out-standing research contributions tobiochemistry and molecular biologyThe recipient must have no more thanten years post-doctoral experienceand the nominees and nominatorsneed not be ASBMB members TheAward consists of a plaque stipendand transportation and expenses topresent a lecture at the 2007 MeetingPrevious recipients of this award wereJM Berger in 2006 Brian Strahl in2005 Pehr A B Harbury in 2004Catherine Drennan in 2003 and in2002 John D York

Burge did his graduate work at Stan-ford in Computational Biology withSam Karlin where he developed awidely acclaimed computational pro-gram Genscan to identify genesequences This and other softwareBurge has produced have beendescribed as probably second only toBLAST in how widely they are used bygenome analysts After Burge com-pleted two years of postdoctoralresearch he became MITMerckBioinformatics Fellow in the Depart-ment of Biology

The nearly unique aspect of Chrisrsquoresearch is the integration of strengthsin computational science and statisticswith a strong personal interest in biol-ogy This interdisciplinary program

Christopher Burge to ReceiveSchering-Plough AwardD

Dr Christopher Burge


he Garvan Institute of MedicalResearch was founded in 1963Initially a research department

of StVincentrsquos Hospital in Sydney it isnow one of Australiarsquos largest medicalresearch institutions with approxi-mately 400 scientists students and sup-port staff The Garvan Institutersquos mainresearch programs are Cancer Diabetesand Obesity Arthritis and ImmunologyOsteoporosis and Neuroscience It ispart of the St Vincentrsquos Hospital Cam-pus and is affiliated with the Universityof New South Wales

The current facilities are only tenyears old and feature an open planlayout of laboratories around an

One of Austral iarsquosT

The Garvan is positioned to the east of theSydney central business district in a trendy

cafeacute suburb called Darlinghurst

GarvanGarvan


recent finding that non-methylatedgenes that reside in a particular lsquosub-urbrsquo near methylated genes aresilenced in cancer whereas untilnow it was thought that only individ-ual single genes were silenced bymethylation In addition Garvanrsquosattention to translational cancerresearch over the last decade hasresulted in several key findings Theseinclude identification of the proteinEDD as a new prognostic marker forearly ovarian cancer relapse whichmay predict the development ofchemoresistance and the finding of anovel prostate cancer marker thathelps identify men whose prostatecancer is likely to spread

Partnerships between the institutersquosneuroscientists and immunologists hasled to the discovery of the mechanismby which neuropeptide Y a moleculethat is proving to have an array of func-tions in different physiological systemscan suppress the immune system Asimilar team effort with scientists in theBone Program revealed the role of NPYand leptin in bone formationmdashresearchthat could possibly result in new treat-ments for osteoporosis

The Garvanrsquos strengths lie in thecalibre of its scientists unique crossdisciplinary collaborations and thebelief that technology is an importantcomponent of competitiveness inmedical science The institution wasthe first in Australia to implement theAffymetrix Microarray TechnologyThe challenge as Garvan continues toexpand is to ensure it retains thedynamics of these fruitful interactionsand keeps up the excitement andmomentum of the research

Assoc iate ProfessorSusan C lark

Professor Clarkruns the epigeneticsgroup in GarvanrsquosCancer programHer interest in sci-ence began with afascination forgrowing seeds Atschool Susanrsquosinterest in botanygrew into other scientific areas buteventually led her to the study of bio-chemistry at Australian National Uni-versity Her postgraduate years at theUniversity of Adelaide were in thedepartment that first introducedrecombinant biology and DNAsequencing to Australia The next movewas into the biotechnology industrywhere Clark again pioneered an Aus-tralian first this time making the firstrecombinant vaccine for porcine diar-rhea which is still used today Clarkwas also involved in producing the firstrecombinant interleukins in mam-malian cells A stint at Cambridge fol-lowed after which Clark returned toAustralia to join the lab of MarianneFrommer The research that followedhas pushed Susan Clark into the inter-national scientific arena Her imple-mentation of the bisulphite sequencingmethod for detecting epigeneticchanges is used around the world andhas spearheaded a new quest for aninternational human lsquoepigenomersquo pro-ject in normal and diseased cells thatgoes far beyond the DNA sequence ofgenome In 2004 Clark received theprestigious German Science Prize theBiochemisch Analytik Preis

atrium that facilitates interactionbetween scientists from differentresearch disciplines The stand-outarchitectural feature is an iconic spiralstaircase that represents the DNA helix

Since its very beginning the Garvanhas placed great importance on com-bining fundamental research discover-ies with clinical outcomes TheBusiness Development Unit providesthe link between Garvan discoveriesand the pharmaceutical and biotech-nology sector In 2006 in one of thelargest commercial deals in Australianbiotech history the Garvan licensed ananti-inflammatory antibody againstthe C5a receptor to the Danish com-pany Novo Nordisk

Research in the 1960s was focussedon diabetes an area in which Garvanhas a strong track record The insti-tutersquos scientists were among the first toshow that abdominal fat is a high riskfactor for type 2 diabetes and thatintra-abdominal fat rather than subcu-taneous fat is the key problemMicroarray analyses of intra-abdomi-nal fat are currently underway to iden-tify proteins with altered levels ininsulin-resistant subjects

The institutersquos collaborations extendto hospitals and academic researchorganizations within Australia andaround the globe The Garvan hasforged links with the Shanghai Insti-tute of Biological Sciences and hasrecently provided biochemical andphysiological evidence to help confirmthat certain traditional Chinese medic-inal plants have beneficial effects forpeople with type 2 diabetes

Cancer research continues to makefundamental discoveries such as the

Largest Medical Research Inst i tut ions

Associate ProfessorSusan Clark


Sydney Harbor and surfing on the local beaches

Assoc iate ProfessorTrevor B iden

Trevor Biden heads the Garvanrsquos Dia-betes Signalling Unit He undertook hisPhD on insulin secretion in Londonfollowing relocation of his mentorrsquos lab-oratory from Sydney University Subse-quently as post-doc with ClaesWollheim in Geneva he was introducedto signal transduction and contributedto early studies characterizing IP3 as asecond messenger Shifting both fieldsand location Biden returned to Australiaand set up a small lab at the Garvanwhere he successfully cloned PKCiotathe last of the PKC family to be discov-ered In ensuing years Bidenrsquos work hascontinued to focus on the nexusbetween signalling cellular functionand the pathophysiology of diabetes beit investigating the molecular mecha-nisms of insulin resistance or pancreaticbeta cell dysfunction He believes thathis current pet projects endoplasmicreticulum stress in beta cells and thesurprising re-emergence of PKC as atherapeutic target for diabetes are someof the most excitingof his career Hefeels fortunate tohave been a part ofthe tremendousdevelopment of theGarvan over thelast 15 years Bidenmay have returned

to Sydney for life-style reasons andcommuting via a harbour ferry contin-ues to hold an attraction but it is the sci-ence that now keeps him here

Dr Robert Br inkRobert Brink recently joined the

Garvan Institute as a group leader inthe rapidly-expanding Immunologyand Inflammation Program Thefocus of his laboratory is B cell devel-opment and antibody production ASydney lad Brink first became inter-ested in the immune system when heattended an undergraduate lecturedescribing the way in which B cells rearrange and mutate theirimmunoglobulin genes in order togenerate antibody diversity For his PhD research he studied the first series of antigen-specificimmunoglobulin transgenic miceand on completion was awarded a CJMartin Overseas Biomedical Fellow-ship But by this time Brink hadbecome severely allergic to mice somuch so that he ended up in a hospi-tal emergency ward His overseaspostdoctoral years were spent at theWhitehead Institute in Boston wherehe furthered his molecular skills andworked on TNF receptors andimmune system signaling moleculesThe late 1990s saw Brink returning toSydney to the Centenary Institutewhere he concentrated on generatingvarious gene-targeted mice for under-standing B cell biology without han-dling them himself These mouse

Professor David JamesThe director of

Garvanrsquos DiabetesProgram DavidJames has spenthis entire scientificcareer studying thelink betweeninsulin receptorsignalling and glu-cose uptake into muscle and fat cellsSince his early days as a Garvan Insti-tute PhD student he has continuedto make valuable contributions tothe field of metabolism But Davidrsquosknowledge of biology was not alwaysso extensive After having failed tobe admitted to medical school andstruggling to pass first year biologyhe ended up taking biochemistry Hehas never looked back While a post-doctoral researcher at Boston Univer-sity in the lab of Paul Pilch and laterwith Mike Mueckler in St LouisJames discovered and cloned theGLUT4 transporter that is found onmuscle and fat cells and is regulatedby insulin Since then he hasfocussed his attention on connectingthe dots between insulin binding toits receptor at the membrane andincreased glucose uptake In 1999James won the Glaxo WellcomeMedal recognizing his contributionto this field This year he receivedthe highest award given by the Aus-tralian Diabetes Society the KellionAward James balances his workloadat the Garvan with kayaking in

Professor David James

Associate ProfessorTrevor Biden

T he Gar van rsquos s t r eng ths l i e in the ca l i b r e o f i t s s c i en t i s t s

un i que c ro s s d i s c i p l inar y c o l l abo ra t i ons and the b e l i e f tha t

t e chn o lo gy i s an impor tant c omponent o f c ompe t i t i v ene s s in

med i ca l s c i enc e


that it is a physiological regulator ofinsulin action They have also found anew role for the cytoskeletal proteincortactin in preventing degradation ofa cell surface receptor involved in can-cer development

Professor John Sh ine FAA AO

John Shine is the Executive Directorof the Garvan institute of MedicalResearch a post he has held since 1990His name is known to most undergrad-uate biology students for his role indefining the Shine-Dalgarno genesequence which is responsible for theinitiation and termination of protein-synthesis However he has a number ofother significant scientific lsquofirstsrsquo underhis belt Shine was a central figure inthe cloning of the insulin and growthhormone genes was the first to clone ahuman hormone gene was responsiblefor cloning of an endorphin gene andwas the first to demonstrate that hor-mone genes cloned in bacteria could beexpressed in a biologically active formHe also determined the first sequenceresponsible for replication of a cancer-causing virus Shine started out doingveterinary science at the University ofSydney for no particular reason at theage of 16 He dropped out when he ranout of money and went to work in thepublic service in Canberra while doinga part-time science degree at the Aus-tralian National University LecturerLynn Dalgarno inspired John in thefield of molecular chemistry despiteShinersquos previous dislike for biochem-istry He went on to do his PhD withDalgarno ndash years that were incrediblyproductive

Shine had the usual share of rejec-tion letters when applying for postdoc-toral positions but ended up with

three options in three different coun-tries and chose San Francisco Thismove in 1975 proved to be one of thebest choices in Shinersquos scientific careerand was where he went on to clonenumerous genes as well as developtechniques to do this for example heis the sole inventor on a patent forusing phosphatase to direct the joiningof DNA molecules

After heading back to Canberra forsix years Shine returned to the Statesand took up ajoint position asan Adjunct Profes-sor of Medicine atUCSF and Directorof Research for anewly formedbiotech CaliforniaBiotechnology IncHe was appointed President of thecompany in 1986 and guided it froma staff of some 15 scientists in 1984to over 200 in 1987 During thisperiod Cal Bio developed severalimportant new therapeutics includ-ing treatments for congestive heartfailure infant respiratory distress syn-drome burns and general woundhealing agents At the same timeShine developed an interest in thegeneration of functional diversity inthe nervous system a research areahe established on joining the Garvan

Science is also an integral part ofShinersquos outside interests He enjoysracing his thoroughbred horses andis fascinated by the art of the sportin particular how genetics and theenvironment come together to deter-mine the horsesrsquo chances of successin a specific race on a certain race-course His scientific successes how-ever havenrsquot been replicated on thetrackmdashyet

models are now providing newinsights into how B cells respond toantigens and survive in the body

Professor Roger Da lyAs a child in England Roger Daly

had lots of science projects on the gofrom growing crystals to collecting fos-sils But an article in Scientific Americanstirred his interest in the molecular andcellular biology of cancer the area inwhich he now works Daly carried outhis PhD studies on cloning oestrogenresponsive genes from breast cancercells at the University of Liverpool UKand continued this theme for his firstpostdoc at what was then the ImperialCancer Research Fund in London Thisled to an interest in growth factoraction and combined with excitingdevelopments in the signalling field inthe late 1980rsquos drew Daly into theanalysis of tyrosine kinase signallingmechanisms His second postdoc withJoseph Schlessinger at New York Uni-versity led to the cloning and charac-terization of Grb2 which established aparadigm for adapter protein sig-nalling This research resulted in a jointfirst author Cell paper that has beencited more than 1000 times Dalyrsquosnext move was to the Garvan Institutein 1993 His Signal Transduction Grouprecently cloned Grb14 and determined

Professor Roger Daly

Professor John Shine


S P O T L I G H T O N A S B M B M E M B E R S

Helen Davies Honoredfor Excellence in MedicalEducat ion

Helen C Davies PhD MS Profes-sor of Microbiology and Ombudsmanfor Students at the University of Penn-sylvania School of Medicine is therecipient of an Alpha Omega Alpha(AOA) Robert J Glaser DistinguishedTeacher Award Davies is being recog-nized by the Association of AmericanMedical Colleges (AAMC) for herefforts to provide the nationrsquos nextgeneration of doctors with an excep-

tional educationalexperience

Daviesrsquo educa-tional efforts havebeen focused onrecruiting mentor-ing and retainingminority groupsand women in biomedical careersFor 35 years she has incorporatedunique methods into her ownlessons to help her students learnand retain information on the symp-toms and mechanisms of variousinfectious diseases Davies writesoriginal song lyrics and performs

them to the tunes of popular songsand her songs are hits among hermedical students One of her morefamous songs ldquoLeprosyrdquo is set to thetune of the Beatlersquos ldquoYesterdayrdquo

During her 40-year teaching careerDavies has achieved many ldquofirstsrdquo Shewas the first female faculty membernamed to Pennrsquos Department of Micro-biology (1965) the first woman facultymember to be designated ldquomaster of acollege houserdquo at Penn (1995-2002)and the first woman to ever receive theAmerican Medical Student Associa-tionrsquos National Excellence in TeachingAward (2001)

Dr Helen Davies

Dill Named forDist inguished Service byBiophysical Socie ty

Ken A Dill University of CaliforniaSan Francisco School of Pharmacy fac-ulty member Associate Dean forResearch and an expert in proteinfolding has been named winner of the2007 Distinguished Service Award bythe Biophysical Society Dill served asPresident of the Society from 1998 to

1999 and currently co-chairs the PublicAffairs Committee

The award recognizes Dillrsquos contribu-tions to the field of biophysics as wellas to the society and in particular hiscontributions to the Bridging the Sci-ences Coalition In 2003 he co-founded the coalition which bringstogether science societies across theUnited States to speak as one voice fordeeper innovation and for federallyfunded research that bridges the physi-calcomputational and the biological

sciences The ulti-mate effect ofdeeper innovationat this interfaceaccording to thecoalition will be themore effective andquantitativeapproaches to discovering drugs andcuring diseases that transcend todayrsquosmore cumbersome lab bench disease-by-disease and molecule-by-moleculeapproaches

Dr Ken A Dill

Wang Elected to RoyalSocie ty of Canada

Yu-Tian Wang of the University ofBritish Columbiarsquos Brain Research Cen-tre has been elected to the Royal Soci-ety of Canada Awarded by theAcademies of Arts Humanities andSciences of Canada Wang joins a totalof 82 new Fellows 2 Foreign Fellowsand 1 Specially Elected FellowFounded in 1882 the Royal Society ofCanada is Canadarsquos oldest scholarlyorganization and election represents

one of the highesthonors for Cana-dian scholars artistsand scientists

In keeping withthe motto of theSociety ldquoDifferentpaths one visionrdquothe newly elected Fellows while com-ing from diverse backgrounds and dis-ciplines are dedicated to achievingexcellence in their endeavors thusenhancing Canadarsquos competitivenesson a global basis

Wangrsquos research has transformedthe understanding of fundamentalmechanisms of synaptic transmissionand neural plasticity serving essentialroles in cognition and emotion Hismost revolutionary discovery demon-strated that dopamine and gamma-aminobutyric acid (GABA) receptorsinfluence each other via protein-pro-tein interactions Wangrsquos discoverieshave been used to guide the develop-ment of novel drugs for modulationof aberrant synaptic plasticity relatedto mental illness

Dr Yu-Tian Wang



Sydney Brenner ReceivesSingapore Nat ionalScience and TechnologyMedal

Nobel Laureate Sydney Brenner Dis-tinguished Professor at the Salk Institutefor Biological Studies was awarded theSingapore Agency for Science Technol-ogy and Research (ASTAR) NationalScience and Technology Medal The

medal which is the highest honorgiven by ASTAR recognized Brennerrsquosdistinguished and strategic contribu-tions to the development of Singaporersquosscientific capability and culture particu-larly in the biomedical sciences sector

Over the past 20 years Brenner whois also Chairman of the ASTAR Biomed-ical Research Council has devoted histime and energy to helping Singaporedevelop into an emerging global hub forbiomedical research He played aninstrumental role in convincing the gov-

ernment to establishthe Institute of Molec-ular and Cell Biology(IMCB) in 1987 Thisproved to be a strate-gic milestone and crit-ical starting point forSingaporersquos efforts todevelop biomedical sciences Brennerserved as Chairman on IMCBrsquos ScientificAdvisory Board from 1987 to 1997 andcontinues to serve as a member on thatboard to this day

Dr Sydney Brenner

Randy Schekman NamedNew Editor of PNAS

Following a review of more than 60nominees the National Academy ofSciences has appointed Randy Schek-man PhD as the new editor-in-chiefof the Proceedings of the National Acad-emy of Sciences (PNAS)

Schekman is Professor of Cell andDevelopmental Biology in the Depart-ment of Molecular and Cell Biology atthe University of California Berkeley

and an investigatorof the HowardHughes MedicalInstitute Elected tothe National Acad-emy of Sciences in1992 Schekmanserved on the editorial board of PNASin 2001-2005 and is currently thechair of the Academyrsquos Biological Sci-ences division

Schekman succeeds former Editor-in-Chief Nicholas R Cozzarelli who died

of Burkittrsquos lymphoma in MarchSolomon H Snyder MD took on addi-tional leadership duties for PNAS duringCozzarellirsquos illness and has served asSenior Editor since January 2005

Schekman whose term runsthrough 2010 said he already has a listof goals and ideas for PNAS Theseinclude seeing a broader range of sci-ence and more integrative science rep-resented in the journal and allowingresearch to be explored in greaterdepth in the articles

Dr Randy Schekman

Seven AS BM B MembersElected to IOM

In October the Institute of Medicineannounced the names of 65 newmembers 7 of whom are members ofASBMB These include

Stephen P Goff PhD investigatorHoward Hughes Medical Institute Hig-gins Professor of Biochemistry andMolecular Biophysics and professor ofmicrobiology Columbia UniversityMedical Center New York City

Susan L Lindquist PhD investiga-tor Howard Hughes Medical Institutemember Whitehead Institute for Bio-medical Research and professor ofbiology Massachusetts Institute ofTechnology Cambridge

Joseph Loscalzo MD PhD HerseyProfessor of the Theory and Practice ofPhysics Harvard Medical School andchair Department of Medicine Brighamand Womenrsquos Hospital Boston

Martha L Ludwig PhD researchbiophysicist and J Lawrence OncleyDistinguished Professor Department ofBiological Chemistry University ofMichigan Ann Arbor

Joan Massagueacute PhD investigatorHoward Hughes Medical Institute andAlfred P Sloan Chair cancer biology andgenetics program Memorial Sloan-Ket-tering Cancer Center New York City

Baldomero M Olivera PhD Distin-guished Professor of Biology Depart-ment of Biology University of UtahSalt Lake City

Ajit P Varki MD DistinguishedProfessor of Medicine and Cellular andMolecular Medicine Department ofMedicine University of CaliforniaSan Diego

The new members raise the totalactive membership of the IOM to 1501Current active IOM members elect newmembers from among candidates nom-inated for their professional achieve-ment and commitment to service Anunusual diversity of talent is assured bythe institutersquos charter which stipulatesthat at least one-quarter of the member-ship be selected from outside the healthprofessions from such fields as the nat-ural social and behavioral sciences aswell as law administration engineeringand the humanities


directed at examin-ing the model forthe architecture ofthe moving replica-tion fork first pro-posed by BruceAlberts of the Uni-versity of Califor-nia San Francisconearly 30 years ago and modified byherself and others in the field Thismodel was based on the T4 phagereplication system termed the ldquoTrom-bone modelrdquo There were two centralaspects of this model which suggesteda solution for the problem that theleading and lagging strands at the forkare synthesized in the same enzymaticdirection but opposite physical direc-tion If the replisome at the fork is asingle large protein machine that repli-cates the DNA Alberts suggested thatthere are two polymerase moleculesone synthesizing the leading strandand one the lagging strand Further heproposed that the lagging strand loopsback at the fork to generate a loopwhich grows and then contractsthrough each cycle of Okazaki frag-ment synthesis hence the analogywith a trombone slide

The presence of a loop at the laggingstrand loop had been visualized in thelate 1990rsquos by Jack Griffith and CharlesRichardson and their colleagues in thesimpler T7 system Working with theGriffith laboratory Nancy Nossal andher group used electron microscopy toexamine the architecture of the mov-ing fork using the more complex T4replication system In one paper pub-lished in Molecular Cell they were ableto examine Okazaki fragment synthe-sis on single replicating DNAs andshow that even at a single moleculelevel the size distribution of Okazaki

fragment length is great and does notfit current models In a paper pub-lished in the Journal of Biological Chem-istry Nossal and colleagues presentedthe long sought-after evidence in thefull T4 system directly demonstratingthe presence of trombone loop at amoving fork Further they showed thatthe single stranded segments at thefork are not extended but present incompact particles bound by the T4 sin-gle strand binding protein

In a paper which will shortly appearin the JBC the Nossal and Griffith lab-oratories applied a new EM methodoriginally developed by Steve Bell atMIT and Griffith in which nano-scaleldquobiopointersrdquo are designed and synthe-sized to detect the presence and loca-tion of specific proteins in a complexDNA-protein complex Using this tech-nology Nossal spent much of her owntime in the laboratory over the pastthree years combining this methodwith classic biochemical approachesHer goal was to test a basic assumptionthat there are indeed two polymerasemolecules at a moving fork The resultspresented in this paper provide thefirst direct proof which has been inwaiting for nearly 30 years that thereare indeed two polymerase moleculesat a moving fork and that in the morerare cases where two Okazaki frag-ments are being synthesized on thesame molecule at the same time threepolymerases could be detected

Griffith noted that Nancy Nossalrepresents the finest example of asenior scientist who by remainingclose to the lab bench herselfbecame not only a leading expert inthe complex field of DNA replicationbut also an invaluable resource oftechnical and scientific insight for allof her colleagues

ancy G Nossal 69 a scientistat the National Institutes ofHealth and former ASBMB

member died September 28 of cancerat her home in Bethesda Dr Nossalwas born in Fall River Mass and grewup in Newton Mass and SyracuseNY She received a bachelorrsquos degreefrom Cornell University in 1958 and adoctorate in biochemistry from theUniversity of Michigan in 1964

She joined the scientific staff atNIH in 1964 and advanced to chiefof the laboratory of molecular andcellular biology at the National Insti-tute of Diabetes and Digestive andKidney Diseases a position she heldat the time of her death In the1960s Dr Nossal became one of thefirst women working in the then-newfield of molecular biology directingher research toward fundamentalquestions about how viruses affectDNA replication and how proteinsfunction at a molecular level

She published more than 60 papersand was on the editorial boards of theJournal of Biological Chemistry and theJournal of Virology She served on anumber of advisory and review com-mittees and in 2005 was elected tomembership in the American Acad-emy of Arts and Sciences

Survivors include her husband of 47years Ralph Nossal of Bethesda threechildren Susan Nossal of MadisonWis Steven Nossal of Reston Virginiaand Michael Nossal of WashingtonDC her mother Dorothy Goldman ofChicago a sister and a brother

Dr Jack Griffith of the University ofNorth Carolina Lineberger CancerCenter whose lab worked closely withDr Nossalrsquos lab recalled that over thepast 10 years a significant portion ofher experimental efforts have been

NNancy Goldman Nossal N IH Scient ist

Dr Nancy G Nossal


September 1 and December 1 witheach issue featuring news from eachof the UAN regions as well as high-lights of student faculty and pro-gram activities and various resourcesand lead articles Each year the UANwill present an outstanding chapterplaque for a school from each regionas well as a national award for thetop chapter in the country

During October and early Novem-ber the North Central North Westand South East UAN regions heldregional undergraduate symposiuafor local schools where travel awardsto the DC national meeting wereawarded to the best undergraduatepresenters at the meeting The NorthCentral meeting was held in con-junction with the Argonne NationalLaboratory Annual Symposium forUndergraduates in Science Engineer-ing and Mathematics and threetravel awards were given to best pre-senters The North West meetingattracted over 80 attendees from sev-eral states and featured 33 under-graduate posters from 10 differentschools Four ASBMB travel awardswere presented The South East eventwas held on Friday October 20 andSaturday October 21 2006 and washosted by the Department of Bio-chemistry at Virginia Common-wealth University (VCU) This eventinvolved presentations of researchprojects performed by studentsenrolled in colleges and universitiesthroughout the Southeast Partici-pants had the opportunity to presentresearch posters to a diverse audi-ence consisting of graduate studentspostdoctoral researchers and facultyfrom VCU and other participatinguniversities Three travel awards werepresented

Next year it is hoped that eachregion of the UAN will host one ormore regional Undergraduate Meet-ing in the fall where travel awards tothe next springs national meetingwill be awarded for best presentationsby undergraduates If you are inter-ested in hosting such a regional meet-ing please contact the ASBMB UANProgram Next year in addition to theUAN and regional meeting travelawards there will still be a number ofcompetitive undergraduate travelawards that any student can apply for

The Saturday at the WashingtonDC National Meeting will again havea major focus on undergraduate par-ticipation and faculty from under-graduate institutions In addition tothe Undergraduate Poster sessionjointly sponsored by EPD and theMinority Affairs Committee therewill be two morning workshopsgeared towards teaching faculty oneon incorporation of outreach andservice learning activities into thecurriculum and the other on usingphysical models to teach proteinstructure function relationshipsThere will be limited space availablein each workshop so be sure to regis-ter for them when you register forthe meting if you are interested

Again this year various GraduatePrograms will be sponsoring recruit-ing tables at the Undergraduate PosterSymposium on Saturday Afternoonwhere both the many undergraduatesattending the session and their facultymentors will have the opportunity tovisit with faculty post docs and gradu-ate students from the participatinggraduate programs If your graduateprogram is interested in sponsoring atable and participating in this eventplease contact ASBMB

ast weekend the Educationand Professional Develop-ment (EPD) Committee

held its annual fall retreat wheremembers gather to discuss a varietyof topics related to education andprofessional development This yearthe EPD met with the UndergraduateAffiliates Network (UAN) Commit-tee and the focus of the meetingswere the new Education and Profes-sional Development Web Site (com-ing soon to a computer near you)and the infrastructure of the UANprogram as well as several potentialinitiatives for the future includingdiscussion of how to enhance tieswith industry interactions with thecommunity college system and out-reach to K-12 particularly focusingon interactions with science teach-ers The committee itself has mem-bers from all aspects of academia aswell as industry and in the past sev-eral years has included representa-tion from both graduate studentsand postdoctoral fellows The UANCommittee two members of whichalso serve on the EPD Committeeconsists of the regional directors ofthe UAN program This year thereare two new members of the UANcommittee Takita Sumter fromWinthrop University who will helprun the Southeast region and DavidPeterson from Texas A amp M who willtake over in the South Centralregion Marilee Benore Parsons fromthe University of Michigan Dear-born who is the North Central UANcoordinator will also assume editor-ial duties for the UAN NewsletterEnzymatic Enzymatic will come outfour times a year with Marilees firstissue being March 1 2007 Subse-quent issues will come out June 1

Inside the Educat ion and ProfessionalDevelopment CommitteeL


S c i e n c e fr o m A S B M B J o u r n a l sBy N ico le Kresge Sc ience Ed i tor

AS BM B Bio Bits

Increased plasma low density lipoprotein cholesterol (LDL-c) level is thought to be the pri-mary risk factor for the development of coronary heart disease and atherosclerosis In humansmore than 70 of LDL-c is removed from plasma by low density lipoprotein receptor (LDLR)-mediated uptake in the liver In previous studies the authors of this paper showed that thecompound berberine (BBR) an alkaloid isolated from the Chinese herb huanglian acts aunique cholesterol-lowering drug that up-regulates hepatic LDLR expression by mRNA stabi-lization Now the authors show that the root extract of goldenseal a BBR-containing medicinalplant is highly effective in up-regulation of liver LDLR expression in HepG2 cells and in reduc-ing plasma cholesterol and LDL-c in hyperlipidemic hamsters with greater activities than thepure compound BBR This higher potency is achieved through concerted actions of multiplebioactive compounds in addition to BBR

Goldenseal administration reduces hepatic fat storage in hyperlipidemic hamsters

The Medicinal Plant Goldenseal is a NaturalLDL-Lowering Agent with Multiple BioactiveComponents and New Action Mechanisms

Parveen Abidi Wei Chen Fredric B Kraemer Hai Li and Jingwen Liu

J Lipid Res 2006 47 2134-2147

Mechanism of Cholesterol Transfer from theNiemann-Pick Type C2 Protein to Model MembranesSupports a Role in Lysosomal Cholesterol TransportSunita R Cheruku Zhi Xu Roxanne Dutia Peter Lobel and Judith Storch

J Biol Chem 2006 281 31594-31604Niemann-Pick type C disease is a lipid storage disorder characterized by the accumulation of unesteri-

fied cholesterol and glycolipids in the endosomallysosomal system The disease is caused by defects ineither of two genes that code for the proteins NPC1 and NPC2 NPC2 is asmall intralysosomal protein that has been characterized biochemically as acholesterol-binding protein Using a fluorescence dequenching assay theauthors of this paper monitored the kinetics of cholesterol transfer from NPC2to model phospholipid membranes They showed that transfer of cholesterolfrom NPC2 likely involves a collisional mechanism and is optimal in an acidicenvironment such as the endosomallysosomal compartment They furtherdemonstrated that NPC2 dramatically increases the rate of transfer of lyso-bis-phosphatidic acid-containing vesicles These studies support a role for theNPC2 protein in the transport of low density lipoprotein-derived cholesterolout of the endosomallysosomal compartment

Potential mechanisms of cholesterol transfer from NPC2 to membranes


S c i e n c e fr o m A S B M B J o u r n a l s

Epigenetic gene silencing can result from modifications in gene expres-sion caused by changes in DNA methylation or chromatin structure In Sac-charomyces cerevisiae DNA polymerase ε (Pol ε) has been shown to bindto double-stranded DNA (dsDNA) and to participate in the stable inheri-tance of the silenced state of chromatin Pol ε is a four-subunit complexthat contains a catalytic subunit Pol2p and three auxiliary subunitsDpb2p Dpb3p and Dpb4p Dpb3p and Dpb4p contain a histone-foldmotif and cells lacking DPB3 andor DPB4 are defective in silencing sug-gesting the subunits involvement in dsDNA binding In this paper theauthors show that neither Pol2p-Dpb2p nor Dpb3p-Dpb4p binds stably to dsDNA but that binding is efficiently reconsti-tuted when the two subassemblies are combined indicating that both complexes are required for stable association withdsDNA Further characterization of mutant forms of Pol ε suggested that the Dpb3p-Dpb4p subassembly in Pol ε bindsdsDNA around its dimeric histone-fold structure in a manner resembling the histone-DNA interaction The Pol ε mutantsalso displayed reduced telomeric silencing suggesting that the dsDNA binding property of Pol ε is required for epigeneticsilencing at telomeres

The small numbers of blood proteins in human serum serveas a substrate pool for cancer-derived proteases which thengenerate cancer-specific serum peptides Following develop-ment of a unique semiautomated serum peptide profilingplatform and after completing investigations to eliminatecommon experimental bias the authors of this paper havenow studied possible effects of gender and age on serum pep-tidomes of 200 healthy men and women ages 20ndash80 and of60 patients (30 men and 30 women) with metastatic thyroidcarcinomas Extensive MALDI-TOF MS and data analysis sug-gests negligible contributions of both age and gender to theserum peptidome patterns except that healthy men andwomen under 35 years but not older individuals could bedistinguished with ~70 accuracy Considering the moreadvanced age of most patients this finding is unlikely tointerfere with peptidomics analysis of most cancers

Serum Peptidome Patterns That DistinguishMetastatic Thyroid Carcinoma from Cancer-free Controls Are Unbiased by Gender and Age

Josep Villanueva Andrew J Martorella Kevin Lawlor John Philip Martin Fleisher Richard J Robbins and Paul Tempst

Mol Cell Proteomics 2006 5 1840-1852

Double-stranded DNA Binding an Unusual Propertyof DNA Polymerase ε Promotes Epigenetic

Silencing in Saccharomyces cerevisiae Toshiaki Tsubota Rie Tajima Kunitomo Ode Hajime Kubota Naoshi Fukuhara Takeshi KawabataSatoko Maki and Hisaji Maki

J Biol Chem 2006 281 32898-32908

Clustering and analysis of peptide profiling data from healthy men and women

DNA polymerase ε binds to double-stranded DNA

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


the way drugs are discovered and devel-opedrdquo said Peter S Kim President ofMerck Research Laboratories

The Nobel Prize in Physiology orMedicine this year went to Andrew ZFire of Stanford University and Craig CMello of the University of Massachu-setts for their discovery of RNAi a nat-ural process that apparently evolved asa way for cells to fight viruses Theawarding of the prize only eight yearsafter the discovery was a sign of howimportant RNAi has become

Merck trying to recover from thewithdrawal of its Vioxx painkiller fromthe market and setbacks on someexperimental drugs is trying to diver-sify beyond pills to other forms ofmedicine In May it agreed to pay $480million to acquire two small compa-nies to help it move into protein drugs

Merck Buys Maker of Gene-Silencing Drugs

by John D Thompson Ed i tor

the province of biotechnology compa-nies like Amgen and Genentech

In RNAi Merck already had a collab-oration with Sirnarsquos chief rival AlnylamPharmaceuticals However Merckexpects that the Alnylam collaborationwould continue

Merck amp Company will pay $11billion to acquire Sirna Therapeuticsone of the leading companies pursu-ing the technology that was the basisfor the 2006 Nobel Prize in medicineshared by Andrew Fire of StanfordUnversiy and the University of Massa-chusetts Craig Mello

The deal is the largest sign yet ofinterest among pharmaceutical com-panies in the technology RNA interfer-ence Merckrsquos all-cash offer for Sirnawas worth $13 a share more than dou-ble Sirnarsquos $645 closing price

RNAi is already used widely in labo-ratories to study the functions of genesbut Merck and Sirna hope the tech-nique may also be used one day to treatdiseasesmdashkilling viruses or tumors forinstance by turning off their genesldquoTherersquos a potential for RNAi to change

Brazil to Expand Sugarcane Output 55 in Six YearsBrazil the worldrsquos largest ethanol

exporter will expand sugarcaneacreage and output by about half overthe next six years as demand for bio-fuel grows supported by made higheroil prices Eduardo Pereira de Carvalhohead of an association representingabout 85 of sugar and ethanol pro-duction in Brazil said cane outputmay rise 55 over the next six years toabout 730 million metric tons whileplanting may grow 45 to about 9million hectares (222 million acres)

A doubling of oil prices over thepast three years which raised the costof gasoline has boosted demand forethanol in Brazil and the US whileJapan and other countries plan to startusing the biofuel as additive Carvalhosaid he expects the price for a barrel of

oil to remain near or above $60 incoming years encouraging invest-ments in ethanol production in Brazil

ldquoWith oil prices around $60 thetrend is for continuous progress indemand here and abroadrdquo Carvalhochairman of the Center-South Sugarand Ethanol Industry AssociationldquoWe will have the incentive to con-tinue to boost ethanol productionrdquo

Brazilian ethanol exports jumped91 percent last month from a yearearlier to 545 million liters (144 mil-lion gallons) on surging demandfrom the US the Trade Ministry saidon its Web site today

Carvalho said he expects annualethanol exports to rise to 7 billion litersover the next six years from 31 billionliters in the crop year ending next April

Cloning Bill SqueezesThrough Australian Senate

The Australian Senate passed thehuman embryo cloning legislation lastmonth but deleted a controversialprovision that would have allowed theuse of animal eggs in the procedureSenators voted 34 to 32 in favor of thelegislation a tighter result than the ini-tial vote earlier that day

The vote came after the legislationrsquosmajor advocates agreed to a proposal todisallow the use of animal eggs - a movecritics have described as opening theway to animal-human hybridsThe Aus-tralian Democrats Andrew Bartlett saidhe proposed the amendment becausescientists had indicated research waspossible without the use of animal eggsHe told the Herald newspaper earlierthat he was still wrestling with the viewconveyed by the legislation thatembryos created by cloning ldquohave lesserintrinsic value than an embryo createdthrough a sperm and an eggrdquo

The Senate also agreed to amend-ments including a proposal for a compre-hensive review and tougher penaltieswhich mean anyone offering to pay for ahuman egg sperm or embryo faces 15yearsrsquo jail Democrat Senator NatashaStott Despoja said she trusted scientists todo the right thing and the bill wouldgive them the tools to embark on ldquosomepotentially dazzling researchrdquo

tion drug Cialis for $21 billion incash Big Biotech also got into thegame And in mid-October GenzymeCorp agreeing to pay $580 million incash for the development-stage com-pany The attraction said Genzymewas AnorMedrsquos Phase III drug candi-date Mozobil which is being tested foruse in stem cell transplantation in can-cer patients

According to Hassan the takeovercraze has been fueled by recent rash ofpatent expirations on some of the indus-tryrsquos biggest-grossing products such asMerckrsquos Zocor Bristol-Myersrsquo Pravacholand Pfizerrsquos Zoloft ldquoThe industryrsquos RampDengines are struggling to keep up withthe expirationsrdquo said Hassan notingthat the trend towards acquisitions hasbeen in place for some time

Hassan added that the windfalls seenby companies under the AmericanJobs Creation Act of 2004 whichallowed US companies to repatriateforeign profits at a special tax rate hasalso powered the trend Under thatmeasure companies can use the cashfor such purposes as mergers andacquisitions

As for Schering-Plough Hassan saidthe company doesnrsquot feel as strong aneed to make a major merger or acqui-sition deal ldquoas our existing products[patents] go into the next decaderdquo IfSchering-Plough were to pursue anacquisition he added it would be tocomplement its existing therapeuticproduct areas cancer inflammatory ill-nesses hepatitis C cholesterol-mainte-nance and respiratory conditions

ldquoThe prices that are being paid byour competitors are breath-takingrdquosaid Schering-Plough Corp Chief Exec-utive Officer Fred HassanHassan in arecent interview with MarketWatchldquoThey wouldrsquove been unthinkable fiveyears agordquo

Indeed the price tags attached to themost recent deals appear to underscoreHassanrsquos observations Note Merckrsquosrecent announced that it was paying a102 premium $21 billion in cashfor research group Sirna Therapeuticswhich co-markets its erectile dysfunc-

Schering CEO Tells MarketWatch MampA Prices are lsquoBreath-Takingrsquo



Brigham Young University andDaniel Simmons a researcher in itsDepartment of Chemistry and Biologyhave filed a lawsuit alleging that Mon-santo a precursor company to Pfizermisappropriated Simmonsrsquo research onCOX-2 to develop its blockbusterpainkiller Celebrex

The suit filed against Pfizer in theUS District Court in Salt Lake CityUtah came after more than five yearsof discussions between the parties andfailed efforts at mediation earlier thisyear ldquoWe know what we are dealingwith and we are prepared to perse-vererdquo BYU spokesperson MichaelSmart told The Scientist

According to the plaintiffs Mon-santo entered a contract with BYU andSimmons in 1991 to partner on thedevelopment of painkillers that tar-geted COX-2 but left COX-1 unaf-

fected Simmons and BYU claim thatMonsanto subsequently used theirresearch methodologies and data todevelop Celebrex outside of the part-nership in order to avoid having toshare the profits They are requestingactual and punitive damages and ask-ing that 75 patents be amended toinclude Simmons among the inventors

The suit claims that Simmons firstidentified COX-2 mRNA at the end of1988 while at Harvard UniversityAfter he relocated to BYU the follow-ing year he characterized the gene andsequenced it noting the applicabilityof his discovery immediately Howeverduring contract negotiations the suitcharges that Monsanto ldquowronglyadvised Dr Simmons that he shouldnot patent these items because anysuch patent would not be enforceableor defensiblerdquo

University Sues Pfizer Over COX-2 research

German Firm to BuildNeuroscience Center atSingapore Hospital

German-based BrainLAB AG hassigned a contract with SingaporeHealth Services (SingHealth) for theestablishment of the worldrsquos firstfully digital neuroscience centre atSingapore General Hospital (SGH)The S$26 million project covers theinstallation of a five-suite operatingfacility to be set up in the next 12months For the first time a com-prehensive range of the latest tech-nologies in healthcare will beavailable in one location digitallyintegrated to provide clinicianswith effective access to and intelli-gent management of digital med-ical information From diagnosticsthrough treatment this new infra-structure will provide clinicianswith timely information and moretreatment options resulting in bet-ter-informed medical decisionsand the ability to seamlessly com-bine multiple treatments


F o r Yo u r L a b F o r Yo u r L a b F o r Yo u r L a bThe information in For Your Lab has been provided by manufacturers and suppliers of

laboratory equipment For further information about any of these products l isted

contacts are l isted at the bottom of each panel When contacting any of these

companies please mention that you saw their product in AS BM B Today Please note

that a l isting in AS BM B Today does not imply an endorsement by the American Society

for Biochemistry and Molecular Biology or by any of its members or staff

Manufacturers and suppliers to include your products in For Your Lab contact

Molly at adnetfaseborg or 301-634-7157 (direct) or 1-800-433-2732 ext 7157

2 1 S T C E N T U R Y B I O C H E M I C A L S

For more info please call 87721782385083038222 e-mail us atinfo21stcenturybiocom or visit us at www21stcenturybiocom

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ANTIBODIES FOR IHC AND ICCBethyl is qualifying over 300 polyclonal antibodies to cell signaling molecules for use with Formalin-Fixed Paraffin-Embedded (FFPE) Tissues and Formalin-Fixed Cells Antibodies are packaged with ample antibody to stain 50-250samples depending on optimal antibody concentration and sam-ple type New mdash IHC Accessory Kit (Cat No IHC-101) providesthe reagents and method for sensitive reliable and economicalIHC staining

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For your free copy please call 707-864-0845 or visit httpwwwChemSWcomASBMB-bphtm

NEW White Paper on Best Practices for ManagingLab Chemical Inventory ChemSW Incrsquos latest white paper detailsbest practices in chemical inventorymanagement providing insights toensure system adoption and successfulincorporation into lab processes Reasonswhy systems fail and why they succeedare examined as well as the true costsassociated with chemical inventorymanagement and cost savings that resultwhen such a system is optimized formaximum effectiveness

E X I Q O N

More information Web wwwexiqoncom E-mail supportexiqoncom Phone 781-376-4150

microRNA expression profilingmiRCURYtrade LNA Array microarray slides incorporateExiqonrsquos unique Locked Nucleic Acid (LNAtrade) technologyto provide unrivalled sensitivity and excellent mismatchdiscrimination for short microRNA (miRNA) targets miR-CURYtrade LNA Arrays work on less than 1 microg total RNA (noneed for microRNA enrichment) labeled using the miR-CURYtrade Array labeling kit The miRCURYtrade LNA microar-ray slides can be used in combination with standardmicroarray slides and microarray analysis instrumentsand software Hybridization and wash buffers areincluded


POSTDOCTORAL RESEARCH ASSOCIATEThe Biology Department of BrookhavenNational Laboratory (BNL) currently has aresearch associate position available in thelaboratory of John Shanklin Research willinvolve structure-function relationships ofplant desaturase enzymes The Shanklinlab (httpwwwbiologybnlgovplant-bioshanklinhtml) focuses on under-standing the basic biochemical mecha-nisms of oxygen-dependent diiron lipidmodification enzymes Current workfocuses on the dimeric organization of thedesaturases and understanding the struc-tural basis for regiospecificity A PhD inbiochemistry chemistry or plant biologywith experience in enzymology isrequired Knowledge of molecular biologyis preferred

BNL a scientific research facility oper-ated by Brookhaven Science Associatesunder contract with the US Departmentof Energy is located on Long Island 50miles from New York City It has strongprograms in Physics Chemistry andBiomedicine in addition to Biology It isalso affiliated with the State University ofNew York at Stony Brook (located 15miles away)

Interested candidates should send thefollowing to shanklinbnlgov PhD the-sis title and date granted a list of up tothree most recent publications and thenames and contact information of threereferees Brookhaven National Laboratoryis an equal opportunity employer com-mitted to workforce diversity

East Central UniversityMolecular Biology The Department ofBiology at East Central University(ECU) seeks qualified applicants for theposition of a tenure-track if eligibleAssistant Professor in Biology beginningAugust 2007 ECU is a student-centeredregional state university located in AdaOklahoma

ECU offers thirty-three undergraduatebaccalaureate degree programs in arts andletters business education mathematicsand sciences nursing and the social sci-ences Eight masterrsquos degrees are offeredin education human resources and psy-chology ECUrsquos 4500 students come form24 countries and 34 states About 70 ofthe 165 faculty members hold doctoratesQualified candidates will hold an earneddoctorate in an appropriate biological dis-

and contact information of at least threeindividuals for letters of recommendationto be submitted in electronic format toDr Bob Hutchins Search CommitteeChair Department of Biomedical SciencesTAMUSHSC 3302 Gaston Avenue DallasTX 75246 Emailbhutchinsbcdtamhscedu

Oak Ridge Associated University

POSTDOCTORAL PROJECT INPROTEOMICSAir Force Research Laboratory Requiresexpertise in analysis of biological and pro-teomic samples Activities for this collab-orative effort between the AFRL AppliedBiotechnology Branch and the Dept ofMolecular and Cellular Biochemistry OhioState Univ will be located at the MassSpectrometry amp Proteomics Facility OSUColumbus Ohio For more informationemail JeffreyJohnsonorauorg

POSTDOCTORAL PROJECT INNANOTECHNOLOGY-BASED TARGETEDANTI-VIRAL THERAPEUTICSAir Force Research Laboratory Bioscienceand Protection Division with Wright StateUniversity Fellow will research howmetallic nanomaterials interact with ampinhibit viral proteins and particles usingcell-based in vitro model systems to evalu-ate anti-viral effects and host cell toxicityThe stipend ranges $35000-50000depending on experience and expertiseFor more information emailJeffreyJohnsonorauorg

POSTDOCTORAL FELLOWSHIPS INMOLECULAR BIOLOGY ANDBIOCHEMISTRYThe Naval Health Research CenterDetachment Environmental Health EffectsLaboratory Dayton Ohio has a vacancyfor an outstanding viral cellular or molec-ular biologist in the nanotechnology areaThe Fellow will conduct research on hownanomaterials interact with and inhibitviral proteins and particles using cell-based in vitro model systems For moreinformation emailJeffreyJohnsonorauorg

cipline related to molecular biology Responsibilities include teaching courses

in General Biology Molecular Biology anda course in area of expertise advising biol-ogy majors directing undergraduateresearch writing external funding propos-als serving on departmental and universi-ty committees and other scholarly activi-ties Familiarity with a Real Time PCR andan ABI 310 Genetic Analyzer is desiredEach applicant should submit a letter ofapplication curriculum vitae official tran-scripts (undergraduate and graduate) astatement of teaching philosophy andresearch interests and three letters of rec-ommendation to Dale Hayden Director ofHuman Resources East Central University1100 East 14th Street Ada OK 74820Review of applications will begin immedi-ately and continue until the position isfilled For information about ECU visithttpwwwecokedu AAEOE

Baylor College of Dentistry

FACULTY POSITIONThe Department of Biomedical Sciences

at Baylor College of Dentistry Texas AampMUniversity System Health Science CenterDallas is seeking outstanding candidatesfor a full-time position at the Assistant toAssociate Professor level for either thetenure or non-tenure educator track A PhDin Biochemistry or a related science area isrequired Non-tenure educator track appli-cants must demonstrate considerableteaching experience (preferably in a dentalschool setting) with a record of excellentstudent evaluations Tenure-track appli-cants must demonstrate the ability toestablish an independent research programand procure extramural funding The suc-cessful tenure-track candidate will partici-pate primarily in a team-taughtBiochemistry course to first year dental stu-dents and graduate students for a non-tenure educator track candidate the teach-ing load will include participation in addi-tional courses Current departmentalresearch strengths include genetics anddevelopmental biology of the craniofacialregion and inflammationpainApplications will be reviewed as they arereceived and will continue to be accepteduntil the position is filled

Applications should include a curricu-lum vitae summary of current researchactivities statement of career goals andteaching philosophy along with the names

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


Keystone Symposium on PI 3-Kinase SignalingPathways in Disease

February 15-20 bull Hilton Santa FeHistoric Plaza New MexicoFor information wwwkeystonesymposia orgMeetingViewMeetingscfmbullMeetingID=864infokeystonesymposiaorg Ph 800-253-0685 or 970-262-1230

Keystone Symposia Bioactive Lipids in the Lipidomics Era

February 20-25 bull Taos New MexicoFor information wwwkeystonesymposiaorg

German Society for Fat Science (DGF) OleochemicalsUnder Changing Global Conditions

February 25-27 bull HamburgFor information wwwdgfettdemeetingshamburgindexhtml

M A R C H 2 0 0 7

US HUPO 2007

March 4-8 bullSeattleFor information contactwwwushupoorgEmail USHUPOUSHUPOorg Ph 505-9899-4876

Keystone Symposia Metabolic Syndrome andCardiovascular Risk

March 27-April 1 bull Steamboat Springs ColoradoFor information wwwkeystonesymposiaorg

4th International Symposium on Diabetes andPregnancy

March 29-31 bull Istanbul TurkeyFor information wwwkenescomdip07ref=oldEmail dip07kenescom

RNAi2007 The Expanding Roles of Small RNAs

March 29-30 bull St Annersquos CollegeWoodstock Road Oxford UKOrganizer Dr Muhammad SohailPh +44(0)1865 275231Fx +44(0)1865 275259 (Switchboard)Email MuhammadsohailbiochoxacukwwwlibpubmediacoukConferencesRNAi2007Homehtm

Association for Biomolecular Resource Facilities

Mar 31-April 3 bullTampa Convention Center FloridaFor information contactwwwfaseborgmeetingsdefaulthtmEmail ncopenfaseborg Ph 301-634-7010

D E C E M B E R 2 0 0 6

Second ISN Special Neurochemistry Conference NeuralGlycoproteins and Glycolipids

December 1-5 bull Antigua West IndiesFor information contactwwwisnantigua2006org

19th World Diabetes Congress

December 3ndash7 bull Cape Town South Africa wwwidf2006org

American Society for Cell Biology 46th Annual Meeting

December 9-13 bull San DiegoPh 301-347-9300 Email ascbinfoascborgWebsite wwwascborg

J A N U A R Y 2 0 0 7

BioSysBio 2007 Bioinformatics System BiologySynthetic Biology

Incorporating the Young Bioinformaticians Forum

January 11-13 bull Manchester UKFor informationwwwbiosysbiocomEmail JohnCumbersbiosyscom Ph 44-0-207-617-7824

Sanibel Conference

January 19-22 bull Sundial Beach Resort Sanibel Island FloridaImaging Mass SpectrometryProgram Chairs Richard Caprioli Ron Heeren and MarkusStoeckli For information contact ASMS505-989-4517 asmsasmsorg wwwasmsorg

F E B R U A R Y 2 0 0 7

Keystone Symposium on Ubiquitin and Signaling

February 4-9 bull Big Sky Resort Big Sky MonotanaFor information wwwkeystonesymposiaorgMeetingsViewMeetingscfmbullMeetingID=860infokeystonesymposiaorg Ph 800-253-0685 or 970-262-1230

Proteomics and PathologymdashJoint Congress of theSpanish Proteomics Society and the EuropeanProteomics Association

February 10-14 bull Valencia SpainFor Information wwwproteomics-valencia2007ibvcsicesEmail catedrasgcaces Ph 34-96-197-46-70

Mitosis Spindle Assembly and FunctionA FASEB Summer Research Conference in Honor of Dr B R Brinkley

June 9 -14 bullHyatt Grand Champions Resort and Spa IndianWells CaliforniaApplications from students and post-docs are especially wel-come For additional information contact the organizersDr Conly L Rieder riederwadsworthorg orDr Robert E Palazzo palazrrpiedu

76th Annual EAS CongressEuropean Atherosclerosis Society

June 10-13 bull Helsinki FinlandThe Congress aims to create a stimulating atmosphere forexchange of the latest scientific and clinical knowledge in thefield of atherosclerosis and cardiovascular diseasesDeadline for submission of abstracts November 30 2006For more information contactKenes International EAS 200717 rue du Cendrier PO Box 1726CH-1211 Geneva 1 SwitzerlandPh +41 22 908 0488 Fax +41 22 732 2850Email eas2007kenescomWebsite wwwkenescomeas2007

20th American Peptide Symposiummdash20th JubileePeptides for Youth

June 22-27 bull Montreal CanadaFor information wwwamericanpeptidesocietycomindexaspEmail 20thAPSUMontrealcaPh 819-564-5346

J U LY 2 0 0 7

XXIst Congress of the International Society onThrombosis and Haemostasis

July 6ndash12 2007 bull Geneva Switzerland wwwisth2007com

32nd FEBS Conference Molecular Machines and theirDynamics in Fundamental Cellular Functions

July 7-12 bull Vienna AustriaAbstracts to be considered for lectures must be received byJanuary 31 2007 All presenting authors of abstracts chosenfor a main talk will receive a registration fee waiverFor registration information httpFEBS2007orgFor Sponsor and Exhibitor information EmailInfgofebs2007org

A P R I L 2 0 0 7

3rd European Symposium on Plant Lipids

April 1-4 bull York UKWebsite wwweurofedlipidorgmeetingsindexhtm

Second Workshop on Biophysics of Membrane-activePeptides

April 1ndash4 bull Lisbon Science Museum PortugalThe Lisbon Science Museum includes a 19th century lab and lec-ture room Conference call for papers special theme issue of J PepSci Symposia Membrane-translocating peptides Cell penetrat-ing peptides Membrane-permeabilizing peptides Antimicrobialpeptides Fusogenic peptides and Structure and Dynamics in pep-tide-membrane interaction Plenary lectures Joumlel Schneide Bio-active properties of peptide surfaces Robert HancockAntimicrobial peptides Stuart McLaughlin Electrostatic interac-tion of basic peptides with acidic lipids in membranes Abstract submission January 15 2007 Early registrationJanuary 15 2007 Faculty of Sciences University of LisbonMiguel Castanho PhDwwwbiophysicsmapcom E-mail castanhofculpt

American Society for Biochemistry and MolecularBiology Annual Meeting in Conjunction with EB2007

April 28ndashMay 2 bull Washington DCContact ASBMB 2007 9650 Rockville Pike Bethesda MD20814-3008Ph 301-634-7145Email meetingsasbmborgWebsite wwwasbmborgmeetings

2nd International Congress on Prediabetes and theMetabolic Syndrome

April 25ndash28 2007 bull Barcelona Spain wwwkenescomprediabetes2007 Email prediabetes2007kenescom

M A Y 2 0 0 7

7th International Symposium of the Protein Society

May 12ndash16 2007 bull Stockholm-Uppsala CA Sweden wwwproteinsocietyorgpagespage02bhtm E-mail cyablonskiproteinsocietyorg Tel 301-634-7277

J U N E 2 0 0 7

55th ASMS Conference on Mass Spectrometry

June 3-7 bullIndianapolisFor information contact ASMS 505-989-4517asmsasmsorg wwwasmsorg

Organized by Benjamin F Cravatt The Scripps Research Institute Michael K Rosen University of Texas Southwestern Medical Center and the 2007 ASBMB Program Planning Committee

From Genome to Epigenome ndash Modification and Repairbull Methylating and De-methylating DNAbull Recombining and Modifying DNAbull Making and Re-making DNAbull Telomeres and Telomerase

The Chromosome Cyclebull Centromeres and Kinetochoresbull Chromatin Structure and Remodelingbull Chromosome Duplication and Cohesionbull Chromosome Segregation and Aneuploidy

RNAbull Molecular Recognition and Enzymology of RNAbull RNA-Based Gene Regulationbull Small RNAsbull RNA Modification Mechanism and Function

Protein Synthesis Folding and Turnoverbull Molecular Mechanisms of Protein Biosynthesisbull Co- and Post-Translational Foldingbull Protein Modification and Turnoverbull Ribosome and Translation

Macromolecular Structure and Dynamicsbull Conformational Transitions and

Protein Aggregationbull Experimental and Computational Dynamicsbull Protein-Lipid Interfacebull Structural and Mechanistic Evolution

Enzymes ndash Mechanism and Designbull Structural Enzymologybull The Role of Dynamics in Enzyme Catalysisbull Computational Studies of Mechanistic and

Dynamical Aspects of Enzyme Reactionsbull Enzyme Design

Extracellular Matrix at Multiple Biological Scalesbull Extracellular Matrix at the Cellular Scalebull Extracellular Matrix at the Molecular Scale bull Extracellular Matrix at the Organism Scalebull Extracellular Matrix at the Tissue Scale

Chemical Biologybull Chemical Biology of Cell Deathbull Fragment Based Drug Discoverybull Chemistry and Cell Biology of Natural Products bull Antibiotics for the 21st Century

Metabolismbull Metabolic Sensing and Signalingbull Molecular and Cellular Aspects of Metabolic Diseasebull Mitochondria in Health and Diseasebull Aging and Metabolism

Organelle Dynamicsbull Golgi Structure and Biogenesisbull Membrane Biogenesisbull Mitochondrial Dynamicsbull Nuclear Dynamics

Systems Biologybull Modeling of Cell Systemsbull Molecular Profiling of Cell Systemsbull Proteomics of Cell Systemsbull Mathematical Biology

Minority Affairs Committee Sponsored Symposiabull Best Practices in Program Assessmentbull Infectious Diseases in Minority Populations

ndash Hepatitis Cbull Genetic Diseases in Minority Populations

ndash Sickle Cell Anemiabull Infectious Diseases in Minority Populations

ndash Tuberculosis

Biochemistry and Signaling of Lipidsbull Biogenesis Transport and Compartmentalization

of Lipidsbull Chemical Probes of Lipid Systemsbull Lipids as Transcriptional Regulatorsbull Specific Protein-Lipid Interactions

Signaling Pathways Controlling Cell Structure and Fatebull Cytokine and Growth Factor Signalingbull DNA Damage Signalingbull Cell Cyclebull Signaling to the Cytoskeleton

Public Affairs Advisory Committee Sponsored SymposiumSponsored by EB participating societiesbull NIH at the Crossroads How Diminished Funds

Will Impact Biomedical Research and what Scientists Can Do About it

Education and Professional Development Committee Sponsored Symposiabull Classroom of the Future IIbull Science at Undergraduate Institutionsbull Graduate StudentPostdoctoral Starting

Faculty Transitionsbull Preparing for a Successful Career

in Industry

April 28 ndash May 2 2007 bull Washington DCHeld in conjunction with EB 2007

LIMITED TIME OFFERDecember 1st through midnight December 21st (EST)

Save an extra 10 on every orderPlus get FREE shipping when you spend $25 or more

(see site for details)

Go to wwwbncomasbmbto start your holiday shopping

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HolidayGiftIdeas_2006_1bindd 1 112206 12502 PM


Cell Culture













6 Washington Update

7 NIH News

12 Career Insights


26 ASBMB BioBits

28 Biotech Business

30 For Your Lab


32 Calendar



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J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

US HUPO 2007










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J A N U A R Y 2 0 0 7




Sanibel Conference


F E B R U A R Y 2 0 0 7











J U LY 2 0 0 7





A P R I L 2 0 0 7









M A Y 2 0 0 7



J U N E 2 0 0 7




















ndash Tuberculosis








in Industry



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6 Washington Update

7 NIH News

12 Career Insights


26 ASBMB BioBits

28 Biotech Business

30 For Your Lab


32 Calendar



O N T H E C O V E R


26


10




DESIGN amp LAYOUT




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PHCPHN

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Dr Greg Verdine















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Dr Randy Schekman
























Dr Nancy G Nossal












AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




Sanibel Conference


F E B R U A R Y 2 0 0 7











J U LY 2 0 0 7





A P R I L 2 0 0 7









M A Y 2 0 0 7



J U N E 2 0 0 7




















ndash Tuberculosis








in Industry





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PHCPHN

PHCPHN 2 2 3PLC

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Dr Greg Verdine















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Dr Susan Taylor





















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Dr Helen Davies






Dr Ken A Dill






Dr Yu-Tian Wang








Dr Sydney Brenner








Dr Randy Schekman
























Dr Nancy G Nossal












AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




Sanibel Conference


F E B R U A R Y 2 0 0 7











J U LY 2 0 0 7





A P R I L 2 0 0 7









M A Y 2 0 0 7



J U N E 2 0 0 7




















ndash Tuberculosis








in Industry
































































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N I H N E W S































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PHCPHN 2 2 3PLC

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Dr Helen Davies






Dr Ken A Dill






Dr Yu-Tian Wang








Dr Sydney Brenner








Dr Randy Schekman
























Dr Nancy G Nossal












AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




Sanibel Conference


F E B R U A R Y 2 0 0 7











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J U N E 2 0 0 7




















ndash Tuberculosis








in Industry





















































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N I H N E W S































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Dr Sydney Brenner








Dr Randy Schekman
























Dr Nancy G Nossal












AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




Sanibel Conference


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J U N E 2 0 0 7




















ndash Tuberculosis








in Industry


































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PHCPHN 2 2 3PLC

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F


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Dr Helen Davies






Dr Ken A Dill






Dr Yu-Tian Wang








Dr Sydney Brenner








Dr Randy Schekman
























Dr Nancy G Nossal












AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































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Dr Randy Schekman
























Dr Nancy G Nossal












AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































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F E B R U A R Y 2 0 0 7











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in Industry














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Dr Randy Schekman
























Dr Nancy G Nossal












AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































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M A R C H 2 0 0 7

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J A N U A R Y 2 0 0 7




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F E B R U A R Y 2 0 0 7











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in Industry































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PHCPHN

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TFII-Ikinase

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Dr Sydney Brenner








Dr Randy Schekman
























Dr Nancy G Nossal












AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




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F E B R U A R Y 2 0 0 7











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TFII-Ikinase

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Dr Sydney Brenner








Dr Randy Schekman
























Dr Nancy G Nossal












AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

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F E B R U A R Y 2 0 0 7











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Dr Randy Schekman
























Dr Nancy G Nossal












AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

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Dr Randy Schekman
























Dr Nancy G Nossal












AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































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M A R C H 2 0 0 7

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F E B R U A R Y 2 0 0 7











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Dr Randy Schekman
























Dr Nancy G Nossal












AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































C H E M S W I N C



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M A R C H 2 0 0 7

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Dr Ken A Dill






Dr Yu-Tian Wang








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Dr Randy Schekman
























Dr Nancy G Nossal












AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




Sanibel Conference


F E B R U A R Y 2 0 0 7











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Dr Helen Davies






Dr Ken A Dill






Dr Yu-Tian Wang








Dr Sydney Brenner








Dr Randy Schekman
























Dr Nancy G Nossal












AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




Sanibel Conference


F E B R U A R Y 2 0 0 7











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A P R I L 2 0 0 7









M A Y 2 0 0 7



J U N E 2 0 0 7




















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in Industry













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Dr Susan Taylor





















GarvanGarvan


















































Dr Helen Davies






Dr Ken A Dill






Dr Yu-Tian Wang








Dr Sydney Brenner








Dr Randy Schekman
























Dr Nancy G Nossal












AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




Sanibel Conference


F E B R U A R Y 2 0 0 7











J U LY 2 0 0 7





A P R I L 2 0 0 7









M A Y 2 0 0 7



J U N E 2 0 0 7




















ndash Tuberculosis








in Industry












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Dr Susan Taylor





















GarvanGarvan


















































Dr Helen Davies






Dr Ken A Dill






Dr Yu-Tian Wang








Dr Sydney Brenner








Dr Randy Schekman
























Dr Nancy G Nossal












AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




Sanibel Conference


F E B R U A R Y 2 0 0 7











J U LY 2 0 0 7





A P R I L 2 0 0 7









M A Y 2 0 0 7



J U N E 2 0 0 7




















ndash Tuberculosis








in Industry






















GarvanGarvan


















































Dr Helen Davies






Dr Ken A Dill






Dr Yu-Tian Wang








Dr Sydney Brenner








Dr Randy Schekman
























Dr Nancy G Nossal












AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




Sanibel Conference


F E B R U A R Y 2 0 0 7











J U LY 2 0 0 7





A P R I L 2 0 0 7









M A Y 2 0 0 7



J U N E 2 0 0 7




















ndash Tuberculosis








in Industry









GarvanGarvan


















































Dr Helen Davies






Dr Ken A Dill






Dr Yu-Tian Wang








Dr Sydney Brenner








Dr Randy Schekman
























Dr Nancy G Nossal












AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




Sanibel Conference


F E B R U A R Y 2 0 0 7











J U LY 2 0 0 7





A P R I L 2 0 0 7









M A Y 2 0 0 7



J U N E 2 0 0 7




















ndash Tuberculosis








in Industry



















































Dr Helen Davies






Dr Ken A Dill






Dr Yu-Tian Wang








Dr Sydney Brenner








Dr Randy Schekman
























Dr Nancy G Nossal












AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




Sanibel Conference


F E B R U A R Y 2 0 0 7











J U LY 2 0 0 7





A P R I L 2 0 0 7









M A Y 2 0 0 7



J U N E 2 0 0 7




















ndash Tuberculosis








in Industry






































Dr Helen Davies






Dr Ken A Dill






Dr Yu-Tian Wang








Dr Sydney Brenner








Dr Randy Schekman
























Dr Nancy G Nossal












AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




Sanibel Conference


F E B R U A R Y 2 0 0 7











J U LY 2 0 0 7





A P R I L 2 0 0 7









M A Y 2 0 0 7



J U N E 2 0 0 7




















ndash Tuberculosis








in Industry























Dr Helen Davies






Dr Ken A Dill






Dr Yu-Tian Wang








Dr Sydney Brenner








Dr Randy Schekman
























Dr Nancy G Nossal












AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




Sanibel Conference


F E B R U A R Y 2 0 0 7











J U LY 2 0 0 7





A P R I L 2 0 0 7









M A Y 2 0 0 7



J U N E 2 0 0 7




















ndash Tuberculosis








in Industry










Dr Helen Davies






Dr Ken A Dill






Dr Yu-Tian Wang








Dr Sydney Brenner








Dr Randy Schekman
























Dr Nancy G Nossal












AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




Sanibel Conference


F E B R U A R Y 2 0 0 7











J U LY 2 0 0 7





A P R I L 2 0 0 7









M A Y 2 0 0 7



J U N E 2 0 0 7




















ndash Tuberculosis








in Industry









Dr Sydney Brenner








Dr Randy Schekman
























Dr Nancy G Nossal












AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




Sanibel Conference


F E B R U A R Y 2 0 0 7











J U LY 2 0 0 7





A P R I L 2 0 0 7









M A Y 2 0 0 7



J U N E 2 0 0 7




















ndash Tuberculosis








in Industry















Dr Nancy G Nossal












AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




Sanibel Conference


F E B R U A R Y 2 0 0 7











J U LY 2 0 0 7





A P R I L 2 0 0 7









M A Y 2 0 0 7



J U N E 2 0 0 7




















ndash Tuberculosis








in Industry













AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




Sanibel Conference


F E B R U A R Y 2 0 0 7











J U LY 2 0 0 7





A P R I L 2 0 0 7









M A Y 2 0 0 7



J U N E 2 0 0 7




















ndash Tuberculosis








in Industry




AS BM B Bio Bits





J Lipid Res 2006 47 2134-2147














J Biol Chem 2006 281 32898-32908



























































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




Sanibel Conference


F E B R U A R Y 2 0 0 7











J U LY 2 0 0 7





A P R I L 2 0 0 7









M A Y 2 0 0 7



J U N E 2 0 0 7




















ndash Tuberculosis








in Industry











J Biol Chem 2006 281 32898-32908



























































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




Sanibel Conference


F E B R U A R Y 2 0 0 7











J U LY 2 0 0 7





A P R I L 2 0 0 7









M A Y 2 0 0 7



J U N E 2 0 0 7




















ndash Tuberculosis








in Industry


























































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




Sanibel Conference


F E B R U A R Y 2 0 0 7











J U LY 2 0 0 7





A P R I L 2 0 0 7









M A Y 2 0 0 7



J U N E 2 0 0 7




















ndash Tuberculosis








in Industry



































C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




Sanibel Conference


F E B R U A R Y 2 0 0 7











J U LY 2 0 0 7





A P R I L 2 0 0 7









M A Y 2 0 0 7



J U N E 2 0 0 7




















ndash Tuberculosis








in Industry


















C H E M S W I N C



E X I Q O N




























M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




Sanibel Conference


F E B R U A R Y 2 0 0 7











J U LY 2 0 0 7





A P R I L 2 0 0 7









M A Y 2 0 0 7



J U N E 2 0 0 7




















ndash Tuberculosis








in Industry



























M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




Sanibel Conference


F E B R U A R Y 2 0 0 7











J U LY 2 0 0 7





A P R I L 2 0 0 7









M A Y 2 0 0 7



J U N E 2 0 0 7




















ndash Tuberculosis








in Industry










M A R C H 2 0 0 7

US HUPO 2007










D E C E M B E R 2 0 0 6







J A N U A R Y 2 0 0 7




Sanibel Conference


F E B R U A R Y 2 0 0 7











J U LY 2 0 0 7





A P R I L 2 0 0 7









M A Y 2 0 0 7



J U N E 2 0 0 7




















ndash Tuberculosis








in Industry








J U LY 2 0 0 7





A P R I L 2 0 0 7









M A Y 2 0 0 7



J U N E 2 0 0 7




















ndash Tuberculosis








in Industry



















ndash Tuberculosis








in Industry


Documents

Constituent Society of FASEB AMERICAN SOCIETY FOR ... · This process in no way diminishes the interest of NIH Institutes and Centers in investigator-initiated, unsolicited research