Constituent Society of FASEB AMERICAN SOCIETY FOR ......4 The Welch Foundation: Devoted to Chemistry...

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

w w w . a s b m b . o r gMARCH 2003MARCH 2003

Constituent Society of FASEB


NIH ‘Hits Wall’ InPresident’s Budget0

Purdue ResearchersFind Key To BiologicalClockPage 12

ALSO IN THIS ISSUE

NIH ‘Hits Wall’ InPresident’s BudgetPage 10

Purdue ResearchersFind Key To BiologicalClockPage 12

The

Welch FoundationChemistry Research & Texas

The

Welch FoundationChemistry Research & Texas

Organized by:Joan W. Conaway, Stowers Institute

Ralph A. Bradshaw, UC, Irvine John Walker, Univ. of Missouri, Columbia

Steve Alexander, Univ. of Missouri, Columbia

Stowers Institute For Medical ResearchKansas City, Missouri

May 2–4, 2003

Proteomic Solutions in Cellular andDevelopmental Biology and Medicine

Sponsored by the

ASBMBand the

Stowers Institute forMedical Research

Meeting website: http://www.asbmb.org/meetingsMeeting website: http://www.asbmb.org/meetings

For further information contact:

ASBMB Meetings Office9650 Rockville Pike, Bethesda, MD 20814

Tel: 301-634-7145; Fax: 301-634-7126Email: [email protected]

See page 2 formore information

on this meeting

f e a t u r e s2 Proteomic Solutions in Cellular And

Developmental Biology

10 NIH ‘Hits Wall’ in President’s 2004 Budget Request

12 Purdue Researchers Discover Basis forBiological Clock

14 Protein That Kills Cancer Cells Identified

15 Antibiotic Protein Kills Bacteria

16 Designer Molecules May Fix RNA SplicingDefects

17 ASBMB Graduation Survey

18 NIAID Grant Supports Probe of Innate Immunity

19 Check Our New Website

22 Cutting Large Keyword Searches Down to Size

d e p a r t m e n t s10 News From the Hill

12 Members in the News

20 Biotech Business

24 Calendar


w w w . a s b m b . o r g

15

MARCH 2003, Volume 1, Issue 12

19

O N T H E C O V E R :

4 The WelchFoundation:Devoted toChemistryResearch and Texas

ASBMBToday MARCH 20032

he field of proteomics hasemerged in the post-genomicera as one of the most rapidly

growing and exciting new areas of bio-logical research. It has the capacity ofidentifying the molecular componentsof organelles and other subcellularstructures as well as understanding themyriad of post-translational modifica-tions that control cellular regulatorypathways. Although the “proteomicera” is only beginning, these studiesare already producing excitingadvances in cell and developmentalbiology as well as medicine.

For researchers who need to keep up-to-date on these developments,ASBMB and the Stowers Institute forMedical Research are jointly sponsor-ing a meeting, Proteomic Solutions inCellular and Developmental Biologyand Medicine, May 2-4, at the StowersInstitute in Kansas City, Missouri.

Many recent proteomics meetingshave focused in large part on develop-ing technologies for protein separation,analysis of composition and post-trans-lational modifications, and analysis ofprotein-protein interactions. By apply-ing these new technologies, researchershope to be able to gain insights intohow the myriad of proteins in cells andorganisms function together as inte-grated systems. An important challengeis to devise strategies for the effectiveapplication of the vast amounts of datagenerated in proteomic analyses to theunderstanding of biological pathwaysand systems and how they contributeto human disease.

“The goal of this meeting,” said JoanConaway, Senior Scientist at the Stow-ers Institute for Medical Research andone of the meeting organizers, “is tomove beyond technology by promot-ing discussion of how best to use pro-teomic approaches to address biological

problems, and to analyze the data fromproteomic analyses and effectively inte-grate it with results of more traditional‘hypothesis-driven’ research.”

“This timely meeting promises toreveal the exciting progress in biologyand medicine that has resulted fromthe proteomics revolution of the pastfew years,” said Stephen Alexander,Professor, Division of Biological Sci-ence, University of Missouri, Colum-bia, a member of the team thatplanned the meeting.

“The Stowers meeting was created tomeet the varied interests of the Societyand provide an opportunity to discussproteomics at a small meeting withmultiple purposes,” said Ralph Brad-shaw, Professor, Department of Physi-ology and Biophysics, University ofCalifornia-Irvine, one of the meetingorganizers and Editor of ASBMB’s newjournal, Molecular and Cellular Pro-teomics. “We wanted to do somethingnot being done by others, we wantedto fashion a meeting based on specificissues and applications. This meetingcan be seen as part of a larger fabric ofsmall, focused meetings in the generalfabric of proteomics.

“This meeting,” he added, “alsomeets the need of a more local audi-ence, and is an opportunity for gradstudents and postdocs from the Mid-west in particular to meet with the bestand get some of their work displayed.”

The Stowers Institute has outstandingconference facilities, including a 230-seat auditorium, smaller meeting andconference rooms, space for poster ses-sions, dining facilities, and on-site guestsuites for speakers. Situated in an areaof parks and fountains, the Institute is afew blocks from the neo-classic Nelson-Atkins Museum of Art and the CountryClub Plaza, a vibrant shopping, dining,and entertainment neighborhood.

TProteomic Solut ions in CellularASBMB Today

is a monthly publication of The American Society for

Biochemistry and Molecular Biology

OfficersBettie Sue Masters President

Robert D. Wells Past-President

Albert E. Dahlberg Secretary

Kenneth E. Neet Treasurer

Thomas Blumenthal Councilor

Judith Bond Councilor

William Lennarz Councilor

Alexandra C. Newton Councilor

Merle S. Olson Councilor

Peter Parker Councilor

Cecile M. Pickart Councilor

Cecil B. Pickett Councilor

James T. Stull Councilor

Non-Voting MembersGeorge M. CarmanChair, Meetings Policy Committee

Claudia KentVern L. SchrammCo-chairs, 2003 Program Committee

Marion H. O’LearyJ. Ellis BellCo-chair, Education and ProfessionalDevelopment Committee

William R. BrinkleyChair, Public Affairs Advisory Committee

Phillip A. OrtizChair, Minority Affairs Committee

Herbert TaborEditor, JBC

Ralph A. BradshawEditor, MCP

CommentsPlease direct any comments or questionsconcerning ASBMB Today to:

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

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

ext. 7175 or 301-530-7157, or email [email protected].

Moving Beyond Technology:

MARCH 2003 ASBMBToday 3

May 2-4, 2003Stowers Institute for Medical Research

Kansas City, Missouri

The meeting will begin Friday, May 2 in the evening and end by noon on Sunday, May4. Additional speakers for oral sessions will be selected from the abstracts submitted.Students, postdoctoral fellows, and younger faculty are particularly encouraged to submit a paper for presentation in these sessions. Those who are selected to make oralpresentations will also be encouraged to present a poster.

Keynote Lecture:Richard A. Young, Whitehead Institute for Biomedical Research

P ro t e o m i c S o l u t i o n s i n C e l l B i o l o g y — O r g a n e l l eS t r u c t u re a n d F u n c t i o n a n d S i g n a l i n g P a t h w a y sChair, Steve Alexander, University of Missouri, ColumbiaMichael Rexach, Stanford UniversityJohn J.M. Bergeron, McGill University

P ro t e o m i c S o l u t i o n s i n D e v e l o p m e n t a l B i o l o g yChair, A.J. Marian Walhout, Dana Farber Cancer InstituteMichael Washburn, Torrey Mesa Research InstituteRichard D. Cummings, Univ. of Oklahoma Hlth. Sci. Ctr.

P ro t e o m i c S o l u t i o n s i n M e d i c i n eChair, John Kessler, Northwestern UniversityHubert Hondermarck, Universite des Sciences et Technologies de Lille, FranceSamir Hanash, Univ. of Michigan Med. Sch.

Tentative Meeting Schedule:Friday, May 26:00 - 8:00 p.m.- Registration/Check-in6:30 p.m.- Reception8:00 p.m.- Opening Lecture and Welcome

Saturday, May 37:30 a.m.- 9:00 a.m.- Continental Breakfast9:00 a.m.- 12:00 p.m.- Oral Session12:00 p.m.- 2:00 p.m.- Lunch/Poster Presentations2:00 p.m.- Keynote Lecture3:00 p.m.- 6:00 p.m.- Oral Session

Sunday, May 47:30 a.m.- 9:00 a.m.- Continental Breakfast9:00 a.m.- 12:00 p.m.- Oral Session

ASBMB Meetings Office • 9650 Rockville Pike, Bethesda, MD 20814-3996 USAPh: 301-634-7145 • Fax: 301-634-7126 • Email: [email protected]

and Developmental Biology and MedicineHOTEL RESERVAT IONS—DEADLINE: April 2, 2003

Hotel reservations should be madeby Wednesday, April 2 in order toreceive the discounted meeting rate.Room blocks are currently being heldat the Fairmont Kansas City at thePlaza. Participants should contact thehotel directly to make their housingreservations. Be certain to mention theASBMB/Stowers Meeting to receive theroom rates below.

Fairmont Kansas City at the Plaza401 Ward ParkwayKansas City, Missouri 64112 USA

Global Reservations Center1-800-441-1414Fairmont Kansas City ReservationsDepartment - 816-756-1500

Room Rates:King: $129.00 per night plus taxesDouble: $139.00 per night plus taxes

SUBMISS ION OFABSTRACTS—DEADLINE: March 19, 2003

Membership in the ASBMB is notrequired for submission of an abstract.Speakers for oral sessions will be selectedfrom the abstracts submitted. Students,postdoctoral fellows, and younger faculty are encouraged to submit apaper for presentation in these sessions.

Abstracts must be submitted elec-tronically. There is no abstract submis-sion fee. Early submission isencouraged. Participants may submitmore than one abstract. Abstracts willbe published in a meeting program tobe provided on site.

ASBMB Meetings Office9650 Rockville PikeBethesda, MD 20814-3996 USAPh: 301-634-7145 Fax: 301-634-7126Email: [email protected]

w w w . a s b m b . o r g / m e e t i n g s

Preliminary Program

The Welch Foundation


Dr. Hackerman: The effect of thissupport on academic research institu-tions in this state has been notable. Ithas helped bring and hold hundreds offaculty and thousands of students inchemistry, biochemistry, and chemical

engineering. Also,while the effect ofother forces cannotbe fully dissected,this support hasalso contributednotably to thegrowth of chemicalscience and tech-nology in Texassince the mid-

twentieth century. This statementincludes both quality and quantity. Itis clear to scientists and engineers, hereand elsewhere, that The Welch Foun-dation has been a significant factor.

ASBMB Today: What are your hopesfor the foundation and for chemicalresearch in Texas?

Dr. Hackerman: Inevitably the futureis at best fuzzy. However the changesdue to increased interdisciplinary capa-bilities must lend to a broadening of thearea chemistry covers. Nature isunaware of fields of science, the latterbeing a ‘human invention’ for conven-ience. However, our understanding ofnature grows. Nonetheless, what we callchemical processes will remain identifi-able and we will be able to continue todiscern the somewhat fuzzier bound-aries of the future. With that as a fact,the Foundation’s activities for a reason-ably discernible future are assured.

Reflecting on the Foundation’saccomplishments in its 2002 AnnualReport, Chairman Richard J.V. Johnsonsaid, “I am struck by how much thefield of chemistry research has grownsince the Foundation was first estab-

lished, from increases in governmentaland private funding to new investiga-tive methods that make it possible toexplore complex questions more effec-tively. As research and discovery occurat a faster pace, scientists are usingmore interdisciplinary approaches tosolve complex problems. Yet basicresearch in chemistry remains funda-mental to developing this broaderunderstanding of our universe, and itis clear that the need for support inthis area remains.”

The Foundation’s endeavors includean annual chemistry conference; theNorman Hackerman Award in Chemi-cal Research to rec-ognize a “risingstar” young scien-tist; grants tochemistry depart-ments at small andmedium-sized edu-cational institu-tions in the state;and funding of 41academic chairs inchemistry. The Foundation also pro-vides support at Texas universities for alecture series by prominent visitingchemists, a summer scholar researchprogram for high school students, anda biennial conference for high schoolchemistry teachers.

Sc ient i fic Adv isoryBoard

The Scientific Advisory Boardchaired by Dr. Norman Hackerman iscomprised of nine of the world’s mostrenowned leaders in chemistry andrelated sciences, including five NobelLaureates. This group plays a key rolein the Foundation’s mission, advisingthe board of directors on scientificissues, evaluating proposals for

ne of the oldest and largestprivate sources funding basicresearch in chemistry, the

Robert A. Welch Foundation has, sinceits founding in 1954, become one ofthe United States’ oldest and largestprivate funding sources for chemistry,biochemistry, and chemical engineer-ing research, providing $469 million inresearch and departmental grants, uni-versity chairs, scholarships, lecture-ships, special projects and awards. Thefoundation is unique in that it is theonly foundation in the nation thatprovides funding for chemical researchin just one state—Texas.

Norman Hackerman, a former presi-dent of both Rice University and theUniversity of Texas and the longtimechairman of the Foundation’s Scien-tific Advisory Board, summarized theinstitution’s uniqueness in hisresponse to some questions posed byASBMB Today.

ASBMB Today: The Welch Founda-tion is to our knowledge the onlyfoundation that supports chemicalresearch in a given state, Texas. In yourown words, how do you see this asbenefiting industry and research insti-tutions in the state?

Dr. Hackerman: Welch grants areprovided to support research into hownature functions in the area of itsactivities humans label as chemistry.By this means we hope to improve ourunderstanding of how chemicalprocesses occur and how they can becontrolled. It is expected that such acapacity can be helpful but that is nota specific objective.

ASBMB Today: Have the foundationand its grants been a factor in attract-ing a large number of outstandinginvestigators to Texas?and keepingthem in the state?

OBy John D . Thompson , Ed i tor

Devoted to Chemistry Research

Foundation Chairman Richard J.V. Johnson

Scientific AdvisoryBoard Chairman Norman Hackerman


Awards Recogn izeScientific Achievements

The Welch Foundation recognizesexceptional scientific achievement withtwo awards. The Welch Award in Chem-istry, which includes a $300,000 prizeand a gold medallion, is presented eachyear to an individual who has made life-time contributions to science throughbasic research in chemistry. The$100,000 Norman Hackerman Award ismade on an annual basis, when war-ranted, to a younger scientist conductingchemical research in Texas. This award ismeant not only to recognize the scien-tist’s work, but is also intended as encour-agement to those embarking on careersdedicated to increasing our fundamentalunderstanding of chemistry.

As a result of his pioneering work inunderstanding the fundamentalmolecular properties of cell mem-branes, including those related to theregulation of cholesterol and the acti-vation of the body’s immune system,Stanford University’s Harden M.McConnell, an ASBMB member, wasselected to receive the 2002 WelchAward in Chemistry.

Dr. McConnell, Robert Eckles SwainProfessor of Chemistry Emeritus atStanford University, was recognized forsignificant discoveries in basic sciencewhich he has more recently related tocellular behavior at the molecularlevel. His research has increased ourunderstanding of the interactionsbetween cholesterol and the fatty acidchains of phospholipids, as well as thereactions between proteins and pep-tides by which the body activates itsimmune system.

“These discoveries set the stage forfurther research that will bring newinsights into immune surveillance andin understanding the function of cho-

lesterol in cells,”said Welch Foun-dation ChairmanJohnson.

“Dr. McConnellhas made a seriesof pioneering dis-coveries concern-ing the physicalstate of liquid

membranes, providing principles usedevery day by many scientists,” said Dr.Hackerman. “His combination ofphysical chemistry and biology hasimmediate relevance to contemporaryresearch on cell membranes.”

Designed to recognize and encour-age young chemists in Texas, the inau-gural Norman Hackerman Award inChemical Research was awarded toAndrew R. Barron in 2002. Dr. Barronis the Charles W. Duncan, Jr. – WelchChair in Chemistry and Professor ofMaterials Science at Rice University.

Dr. Barron specializes in the chemistryand materials science of aluminum andits related elements. Research initiativesencompass problems across the fields of traditional inorganic chemistry,organometallic chemistry, nanoscale sci-ence and technology, and materials sci-ence. His research covers the continuumfrom synthesis to application. On theapplication side, Dr. Barron is especiallyinterested in the development of newmaterials and the fabrication of micro-and nano-electronic devices based onmolecular design.

He has developed a new way to makealuminum-oxide ceramics that is moreenvironmentally sensitive, as well ascomposite materials enhanced by nan-otechnology. In collaboration withMark Wiesner, Rice Professor of Civil,Environmental and Chemical Engineer-ing, he also created a nano filter system

research grants, and reviewing allnominations for the Welch Award inChemistry. In addition, the boardhelps oversee the foundation’s visitinglecture series, departmental grants, andother programs.

Nobelists on the Scientific AdvisoryBoard are:

Elias J. Corey, Professor of Chem-istry at Harvard, who received theNobel Prize for Chemistry in 1990.

Joseph L. Gold-stein and MichaelS. Brown the 1985,ASBMB memberswho shared theNobel Prize in Phys-iology or Medicinefor discoveriesrelated to choles-terol metabolism.

Dr. Goldstein is Chairman of theDepartment of Molecular Genetics atthe University of Texas SouthwesternMedical Center, Dallas.

Yuan T. Lee, a recipient of the Nobelfor Chemistry in 1986. Dr. Lee is Presi-dent of Academia Sinica, Taipei, Taiwan.

ASBMB member William N. Lip-scomb, Jr., Professor of ChemistryEmeritus, Harvard University, who wasawarded the Nobel for Chemistry in1976.

Ahmed H. Zewail, the Linus Paul-ing Chair and Professor of Chemistryand Physics, California Institute ofTechnology, who was awarded theNobel for Chemistry in 1999.

Other members of this board areASBMB member Peter B. Dervan, Pro-fessor of Chemistry, California Instituteof Technology; Marye Anne Fox, Chan-cellor, North Carolina State University;and Peter G. Schultz, Professor of Chem-istry, The Scripps Research Institute.

And the State of Texas

Nobelist Joseph Goldstein

Welch Award Recipient Harden M. McConnell



This first-hand experience not onlyteaches students a great deal aboutchemistry, but exposes them to new edu-cation and career options. Many partici-pants are motivated to pursue educationbeyond high school, often continuingtheir work in science and chemistry.

In addition to in-lab work, studentsgain exposure to a guest speaker series,tours of chemistry-based research facili-ties, assignment to an ongoing researchgroup, the presentation of personalresearch findings, and life on a typicaluniversity campus. The common labo-ratory experience is conducted duringthe first week of the program and isdesigned to give students the expecta-tions of a university-level laboratoryexperience. Experiments have includedinorganic synthesis and analysis,organic synthesis and analysis andspectrometric methods of analysis.

Last summer, 53 Texas high schoolstudents took part in the SummerScholar Program at the University ofTexas campuses in Arlington, Austin,and Dallas, and at Texas Tech Univer-sity and the University of Houston.

Teacher ProgramAn important consideration for pre-

college chemistry teaching is the contin-uing education of teachers. The WelchFoundation, recognizing the importanceof a teacher’s role in fostering studentinterest in the sciences, has supportedseveral activities initiated by the Associ-ated Chemistry Teachers of Texas.

In 2002, the Foundation supporteda workshop held at Texas WesleyanUniversity. Forty-three high schoolteachers (31 from Texas) participatedin this intense workshop, which isspecifically tailored to the needs ofhigh school and junior high schoolchemistry and science. The workshopfocused on enhancing the teacher’s

that could be used in hazardous wastetreatment, biomedical separations, andto control the spread of viruses.

Quantum ChemistryTakes Center Stageat We lch Chemica lResearch Conference

Recent developments in computertechnology and sophisticated theoryhave dramatically increased the scopeand power of quantum chemistry andits ability to shed light on complexchemical problems. More than 400 sci-entists from around the world con-vened in Houston last October tofurther explore these capabilities atThe Welch Foundation’s 46th Confer-ence on Chemical Research, “Advancesin Quantum Chemistry.”

“It was exciting to see so many excel-lent quantum chemists gather togetherand discuss this subject,” said confer-ence chairman Yuan T. Lee, “Chemistryhas long been an experimental science,but these new tools provide a founda-tion for analytical approaches to verycomplex problems.”

The 2003 Welch Conference onChemical Research, “Chemistry inTexas: Fifty Years of The Welch Foun-dation,” will be held October 27-28 atthe Wyndham Greenspoint Hotel inHouston.

Welch ProgramsEnr ich Chemica lResearch , Educat ionResearch Grants

In 2002, the Foundation awarded$19.3 million in grants to 126researchers?renewing support for 106projects and funding 20 new propos-als. Currently, 452 principal investiga-tors receive Welch funding, bringingtotal Foundation support for chemicalresearch to $469 million since 1954.

Each research grant is renewable basedon a proposal and provides a mini-mum of $150,000 over three years.

Departmental GrantsIn the past year, 40 chemistry depart-

ments at small- and medium-sizedTexas educational institutions receivedWelch department grants. These grantsfund scholarships and provide labequipment and supplies for faculty andstudent research. By providing studentswith first-hand experience in basicresearch and the opportunity to partici-pate in industry meetings and confer-ences, the Foundation hopes to furthertheir interest in chemistry.

Welch ChairsIn addition to providing departmental

grants, the Foundation currently endows41 chairs in chemistry at 20 Texas institu-tions. These chaired positions attractsome of the world’s most renownednames in science, enhancing chemicalresearch and education statewide.

Visiting Lecture SeriesEach year, students and faculty at var-

ious Texas colleges and universitiesenhance their chemistry studies byattending a visiting lecture series hostedby The Welch Foundation. These lec-tures feature some of the best scientificminds in the world sharing their insightand knowledge about various areas ofchemistry. For the 2001-2002 academicyear, eight scientists made presentationsat 24 universities across Texas.

Summer Scholar ProgramThe Welch Summer Scholar Program

has for the past 18 years provided highschool students the opportunity towork with faculty researchers in theirlaboratories at Texas university cam-puses for five weeks.


The Robert A. Welch Foundation hashad a profound impact on the qualityof research in chemistry in Texas. TheWelch Foundation supports severaltypes of programs including EndowedChairs for distinguished faculty, researchgrants for scientists at Texas institutionsin chemistry, chemical engineering, andbiochemistry as well as sponsoring theannual Welch Award.

The Robert A. Welch EndowedChair in Chemistry at the Institute ofBiosciences and Technology, which Ihold, was a major factor in attractingme to move to Texas in 1990, and hascertainly been a positive factor in myretention since resigning the InstituteDirectorship in 1994. The WelchFoundation provides Endowed Chairsto judiciously chosen institutions whothen identify an excellent scientist forrecruitment, generally outside thestate of Texas. Thus, this mechanismhas served an important role instrengthening chemically relatedresearch within the state. In additionto the Welch Endowed Chairs, theFoundation has provided almost $500million in chemical research grants to69 Texas institutions since the mid

1950s. In 2001, itcontributed over$22 million inresearch grants to135 researchers.Thus, these fundsmay be used for salaries, equip-ment, supplies,travel, etc., and, therefore, serve as awonderful contribution to researchprograms that are otherwise ade-quately funded.

The Robert A. Welch Award andthe Annual Meeting are highlights ofthe Texas chemical academic yearand a large number of members ofthe ASBMB have been recognized bythis fine award (discussed above).

To the best of my knowledge, thisis the sole foundation in the U.S. thatprovides funds for chemical researchin a single state.

In summary, the impact of theRobert A. Welch Foundation on thequality of chemical research in Texashas been enormous.

The research supported by theFoundation in my laboratory focuseson the biochemical properties of long

triplet repeats of GAA•TTC which areinvolved in the etiology of a devastat-ing hereditary neurological diseasenamed Friedreich’s ataxia. A majordiscovery over the past 10 years hasbeen the genetic expansion of simple triplet repeat sequences (CTG•CAG,CGG•CCG, and GAA•TTC) for theindicated diseases. Normal individu-als have short repeat sequenceswhereas patients contain greatlyexpanded triplet repeat tracts. Theprocesses of replication, DNA repair,and recombination mediate theseexpansions and deletions are themajor focus of my laboratory. Inaddition, we are quite interested inthe chemistry of the DNA conforma-tions adopted by these sequences,especially the GAA•TTC tract inFriedreich’s ataxia which forms a longthree-stranded structure (triplex)named sticky DNA. Sticky DNA is anovel conformation found in Friedre-ich’s ataxia sequences that causes twosegments of DNA to tightly adhere toeach other. Our present emphasis isin addressing the physiological func-tions of this unusual DNA structurein the disease etiology.

Robert D. Wells

The Welch Foundat ion’s Impact on Research in Texasby Dr. Robert D . We l l s , Past Pres ident of ASBMB and Pres ident-E lect of FASEB .

knowledge of using chemical demon-strations, participation in hands-onlaboratory activities, and meetingNational Education Science Standardsfor chemistry.

The Welch LegacyThe Welch Foundation is a legacy to

the world from Robert Alonzo Welch, aself-made man with a strong sense ofresponsibility to humankind, an

enthusiastic respect for chemistry anda deep love for the state of Texas.

Born in South Carolina to a promi-nent family that fell on hard economictimes, Mr. Welch came to Houston as ayouth and later made his fortune in oiland minerals. Over the course of hiscareer and life, he became convincedthat the pursuit of chemistry and chemi-cal research held great potential for vastgood and would continue to have a valu-

able impact on business, industry, globalleadership and the human condition.

In his will, Welch stated, “I have longbeen impressed with the great possibili-ties for the betterment of mankind thatlay in the field of research in thedomain of chemistry.” With his deathin 1952, he left a generous portion ofhis estate to his employees and theirfamilies. The balance began what isnow The Welch Foundation.



of nitric oxide synthase after havingspent most of my experimental life inresearch on NADPH-cytochrome P450reductase and a subfamily ofcytochromes P450 catalyzing fatty acidand prostaglandin oxygenation. With-out these additional resources, it wouldnot have been possible to begin thisentirely new research program.

During the years I have been eligiblefor Welch funding, as a faculty mem-

ber of a Texas academic institution, Ihave received continuous supportfrom The Robert A. Welch Foundation.Many of my colleagues in other stateshave been envious of this opportunityas they see it as a stability factor and analternative support mechanism for thetraining of students and postdoctoralfellows. I have been honored andblessed by the largesse of this remark-able foundation.

oon after I began my inde-pendent career as an AssistantProfessor at the University of

Texas Southwestern Medical School, Ireceived a research grant from TheRobert A. Welch Foundation. The Bio-chemistry Department at Southwesternwas the only one in the institution privi-leged at that time to be granted suchawards due to our chemical heritage.Robert A. Welch, after all, had endowedresearch in chemistry only in the state ofTexas in his will. This award meant thatwe could hire a postdoctoral fellow andsupport a graduate student or an under-graduate research scholar or it could beused to bolster our funding levels tomake it possible to fund an extra item ofequipment or simply to provide somestability to our laboratory enterpriseswhen other sources fluctuated.

In the 1970’s, the Robert A. WelchFoundation Chairs in Chemistry wereestablished. This offered certain institu-tions that received Welch grant fundingthe opportunity to recruit outstandingresearch investigators from out of state totheir respective campuses with generousendowments. I was a member of thecommittee to select such an individualin Dallas but the mission was not accom-plished before I left to become Chair ofBiochemistry at the Medical College ofWisconsin in 1982. It never occurred tome that I would become a recipient ofone of these endowments some 8 yearslater. In 1990, I was recruited from Wis-consin to become the first Robert A.Welch Chair in Chemistry in the Depart-ment of Biochemistry at the Universityof Texas Health Science Center in SanAntonio. The decision to assume thatposition has been one of the most posi-tive of my life. With these supplementalfunds, it was possible for me to embarkupon an entirely new area of researchinvolving studies of the various isoforms

S

A Source of Stabil i tyby Dr. Bett ie Sue Masters , ASBMB Pres ident .

Multitasking with papers under her arm and headset on for teleconferencing is Bettie Sue Masters,Robert Welch Foundation Professor of Chemistry at the University of Texas Health Science Center in

San Antonio. With her are Laboratory Director and Senior Research Associate Tom Shea, in sus-penders, and Pavel Martasek, M.D., Ph.D. The latter, said Dr. Masters, “is pointing to the flasks to

guide my hands. My lab colleagues are always fearful when they see me in lab mode—a little rusty.”

New ASBMB Member BenefitFree Subscription to MCP Online

Activate your subscription today at:http://www.mcponline.org/subscriptions

Your customer number is included on your 2003ASBMB membership card.

Questions? Contact the ASBMB subscriptions office:Tel: 301-634-7140 Fax: 301-634-7108

[email protected]


r. Leroy Hood, President of theInstitute for Systems Biology,Seattle, was presented with the

Kyoto Prize for advanced technology inthe field of Biotechnology and MedicalTechnology. Dr. Hood received theaward at a special ceremony last Novem-ber in Kyoto, Japan, and delivered hislaureate presentation in March at theSecond Annual Kyoto Laureate Sympo-sium at the University of San Diego.

The Kyoto Prize recognized Dr.Hood’s “outstanding contribution tolife sciences through the developmentof automated instruments for thedetermination of protein and DNAsequences and their syntheses.” Hedeveloped an automated peptidesequencer approximately 100 timesmore sensitive than previous instru-ments, as well as automated peptideand DNA synthesizers and an auto-mated fluorescence DNA sequencer.Through these achievements, he hasmade a substantial contribution toprogress in life science and today’sadvances in human genome science.

Dr. Hood conceived and realized theuse of automated instruments inmolecular biology and molecular

genetics, fields which had hithertodepended primarily on the technicalprowess of scientists. Through suchinnovations, he helped complete thesequencing of the human genome, anextraordinary contribution to theadvancement of life science and onethat had initially been predicted totake nearly a century to accomplish.

In the 1970s, scientists made impor-tant steps in the field of genetic engi-neering, foremost among which wereDNA fragmentation and cloning andthe subsequent technology of DNAsequencing. Such methods, however,required considerable time and skill onthe part of scientists. Dr. Hood devel-oped a high-speed, highly-sensitivepeptide sequencer, making it possibleto automatically determine the aminoacid sequence of amino acids withinproteins, key components of thehuman body. The dramaticallyincreased sensitivity of this sequencer,which employed phase-based couplingand cleavage steps, allowed scientistsfor the first time to analyze trace pro-teins in living organisms.

In 1984, Dr. Hood pioneered an auto-mated peptide synthesizer and an auto-

AS BM B Member Receives Kyoto Prize

AS BM B Welcomes New Ph.D.sASBMB extends its congratulations to these individuals who recently received

their Ph.D. degrees. In recognition of their achievement, ASBMB is presentingthem with a free one-year membership in the Society. The new Ph.D.s are listedbelow with the institution from which they received their degree.

Dayle K. BlencoweCardiff University School of Biosciences

Steven M. ClaypoolHarvard University

Amy L. HaasHarvard University

Christina A. JohnsonUniversity of California, San Diego

Andrew W. KinleyUniversity of Virginia

Zhiqiang LuUniversity of Arkansas

Michael A. A. MathewsUniversity of Utah

Jalil MehrzagGhent University

Steven C. PohnertDuke University

Xinye YinUniversity of Texas Health Science Center

mated DNA syn-thesizer. The lattertechnology con-tributed to therapid diffusion ofPCR (PolymeraseChain Reaction), aDNA amplificationtechnique devel-oped around thesame time. These important innova-tions facilitated and stimulated the sub-sequent remarkable progress in all areasof DNA and protein research. In 1986,he announced the world’s first auto-mated fluorescent DNA sequencer, agroundbreaking invention that madethe deciphering of three billion geneticcodes an attainable goal. This automa-tion drastically reduced the timerequired for sequence determinationand formed the prototype for the capil-lary DNA sequencer widely used today.

A working draft of the entire humangenome sequence was published in 2001and the complete sequence will be pub-lished later this year. This rapid advance-ment of the Human Genome Projectwas made possible in large part by Dr.Hood’s DNA synthesizer and sequencer.

The progress and achievements ofgenomics are expected to lead to rev-olutionary new medical applications,such as the development of powerfulDNA diagnostics methods for predic-tive medicine. specification of opti-mal methods of treatment forindividuals. In addition, the deci-phering of genetic information forother species will undoubtedly facili-tate the development of solutions forthe food crisis and environmentalproblems as well as provide impor-tant insights into the history of lifeevolution. The various high-speed,automated instruments pioneered byDr. Hood have been fundamental toprogress in genomic science andmodern biology.

D

Kyoto Prize WinnerLeroy Hood

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


more robust pace. For example, the2003 budget included almost $1.4 bil-lion in facilities construction (on andoff the NIH campus) and anthrax vac-cine procurement. These one-time costswere paid for last year and funds in the2004 budget have been reallocated tosupport research, expenditures forwhich grow by 7.5% in the new budget.

However, these additional researchexpenditures are targeted. A total of 322new and competing grants are fullyfunded in 2004, for over $179 million.

In addition, the number of biodefense-related research grants has doubledfrom last year, to 661. The number ofnew and competing grants that are notbiodefense-related rises only slightly—9,848 in 2004, a gain of just 19. The sizeof grants will also increase slightly—competing renewal grants will be upabout 1%, and noncompeting grants2.7%. In short, nonbiodefense-relatedresearch expenditures rise at only abouta 4% rate in the budget proposal.

In his January 28 State of the Union,President Bush noted that the skill andinnovation of American medicine gen-

erates “a pace of discovery that isadding good years to our lives.” How-ever, a 2% increase at NIH fails to rec-ognize those factors required to ensurecontinued progress toward betterhealth and improved quality of life.These include maintaining currentresearch efforts, producing new ideas,and the development of technologiesneeded to sustain medical progress.

While biomedical researchersexpressed gratitude to the President forhis strong support of the doubling cam-paign (which is slated to end in FY2003), the new proposal falls well shortof the 8% to 10% increase mostobservers believe NIH needs to maintainbiomedical research at some reasonablelevel. ASBMB, along with FASEB, the AdHoc Group for Medical Research Fund-ing, and most other biomedical researchadvocacy groups, is supporting a 10%increase in NIH funding for 2004.

Of the NIH budget proposal, ASBMBPresident Bettie Sue Masters said, “Weare grateful to the President for hislong-standing support for doubling theNIH budget and are pleased that hisproposal assumes that Congress willcomplete the doubling on time. How-ever, the proposed 2% increase for the2004 budget is disappointing, andmarks the beginning of an erosion ofNIH’s research capacity just at thepoint when the doubling has beenlargely completed. Several years ofsuch increases would largely eliminatethe effect of the generous appropria-tions supported by two Presidents andlarge bipartisan majorities in Congress

he Administration has pro-posed a 2% increase for NIHin the federal budget for fiscal

year 2004. The NIH budget wouldincrease $549 million, to almost $27.9billion. While the proposed increase isconsiderably larger than the 0.2%increase floated as a trial balloon latelast year, it is still a disappointing (butnot unexpected) proposal after almostfive years of multi-billion dollarincreases in connection with the NIHdoubling campaign begun in 1999.

In an unusual sequence of events,the President’s budget for fiscal 2004was made public about 10 days beforethe fiscal 2003 budget was finalized.However, the President’s 2004 propos-als for all unfunded agencies werebased on his FY 2003 budget proposalsmade a year ago. The President hadproposed that NIH receive a 15%increase in 2003; his 2004 proposal wasbased on the assumption that Congresswould complete the doubling of theNIH budget in fiscal 2003, which it didjust before Valentine’s Day. Thus, theincrease for NIH in the President’s 2004proposal does not need to be recalcu-lated, as it does for many other agen-cies the budgets for which did notincrease at the rate proposed in his2003 budget (see the discussion of the2003 budgets for NIH and NSF in theaccompanying sidebar).

While the President’s 2004 proposalcalls for only a 2% increase overall,there have been shifts within thebudget from last year to this to keepresearch project grants growing at a

N I H ‘Hits Wall ’ in President’s2004 Budget Request

By Peter Farnham , Pub l i c A f fa i rs O f ficer

T

“The proposed 2%increase for the 2004 budget isdisappointing, andmarks the beginningof an erosion of NIH’sresearch capacity…“

—Bet t i e Sue Mas t e r s ,ASBMB Pre s ident


NSF continues to work towardincreasing the size and duration of itsresearch grants, and has adopted thegoal of average NSF grants amountingto $250,000 per year for five years.Although it has a long way to go toreach that goal, slow progress contin-ues this year. The average grant in2004 is expected to be $128,000.

In addition to core research programs,NSF is supporting significant work in sixpriority areas: Biocomplexity in the Envi-ronment ($99.8 million); InformationTechnology Research ($302.6 million);

Nanoscale Science and Engineering ($249million); Mathematical Sciences ($89 mil-lion); Human and Social Dynamics($24.2 million); and a Workforce for the21st Century initiative ($8.5 million).

Funding will also be targeted towardhomeland security research, researchon climate change, and the establish-ment of three to five centers to focuson the science of learning.

More detailed information on the NSFbudget proposal for 2004 can be foundon its website, at: http://www.nsf.gov/home/budget/start.htm

since 1998. It is even more imperativein this time of uncertainty that thevery underpinnings of the health ofU.S. citizens be maintained over anextended period at a level that will sus-tain the progress that has been made,albeit somewhat less than during thedoubling years. This cannot be donewith an increase of merely 2% as com-pared to 13% to15%. Therefore,ASBMB and most of the biomedicalresearch community are supporting anincrease for NIH of approximately 10%in the 2004 budget in order to sustainthe magnificent research engine thathas been created at NIH.”

A detailed document laying out thePresident’s 2004 proposal for NIH isavailable on the NIH website, athttp://www.nih.gov/news/budgetfy2004/fy2004presidentsbudget.pdf

NSF Fares L i tt leBetter

Regarding NSF, the President asked fora 9% increase to $5.48 billion in 2004.This is about $450 million above theAdministration’s request of $5.03 billionfor the agency in fiscal 2003. However,Congress approved on February 13 a$5.3 billion budget for NSF for 2003, sothe President’s request for 2004 hasalready been overtaken by events. Takinginto account the 2003 appropriation, thePresident’s proposal amounts to a 3.2%increase, not a 9% increase (see accompa-nying sidebar for more detail).

The agency’s core research programsare up slightly over 2003, with Researchand Related Activities increasing by1.2% to $4.1 billion of NSF’s total. Extraemphasis is placed this year in the areaof mathematics and physical sciences.For the first time, the research pro-grams in this area collectively amountto more than $1 billion. The BiologicalSciences Directorate (BIO) actuallyshrinks under the President’s proposal;he proposed a total of $562 million forBIO, but Congress had alreadyapproved $571 million for BIO in 2003.

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

The 2003 appropriations process isfinally complete (although well overfour months behind schedule).House, Senate, and White Housenegotiators hammered out a 2003omnibus spending bill in early Febru-ary that was approved by both Houseand Senate on February 13 and sentto the President for his signature.

In even better news, the NationalInstitutes of Health budget will beofficially doubled. In the agreement,NIH receives almost $3.8 billion inadditional money over the 2002level—a 15% increase that puts it at$27.2 billion. However, once varioustaps, salary cuts and other allocationsare taken into account, the effectiveprogram budget for NIH is about$26.4 billion. These reductionsinclude $100 million for global AIDS;$176 million to cover a 0.65% across-the-board cut in all agencies in theomnibus bill; and $507 million for a“program evaluation” tap (largely atransfer to other HHS agencies suchas the Agency for Healthcare Researchand Quality). On the other hand, $74million is transferred from EPA forresearch at the National Institute ofEnvironmental Health Sciences.

PAAC Chair Bill Brinkley said uponhearing the news, “We all can declarevictory on this remarkable five-yearcampaign. The bill is not expected tohave any changes when it goes toCongress for signature and to thePresident’s desk. Victory at last! Kudosto our champions on the Hill and allwho worked to make this possible.”

The National Science Foundationalso fares well. NSF receives an 11.6%increase in the omnibus bill, with theFoundation’s research programs ris-ing 13.5%. Last September, when anNSF appropriation bill finally beganto move in the Senate, ASBMB Presi-dent Bettie Sue Masters wrote to Sen-ators Mikulski and Bond expressingconcern about the disparity betweenwhat had been proposed for most ofthe research programs at NSF (in thedouble-digits on a percentage basis)and the biological sciences direc-torate (about 3.5%). That disparityhas been eliminated; BIO gets a13.1% increase, the same as the otherresearch directorates.

Tables from NIH and NSF showingthe fiscal 2003 appropriations areavailable for viewing on the publicaffairs page of the ASBMB website.

2003 Appropriat ions Clear Congress; N IH Completes 5-Year Doubling Campaign


M E M B E R S I N T H E N E W S

prove anything conclusively, though,so the physicists had a field day argu-ing about it.”

The argument was more than just anintellectual exercise. Even in the early1960s, scientists knew that cancerpatients and the elderly often experi-enced disorders thought to be relatedto the biological clock. As time passed,it also became clear that astronauts suf-fered bone loss and muscle wastagedue, in part, to space travel’s effects ontheir internal clocks, and air travelersbegan experiencing the clock-relatedailment of jet lag.

“We knew little for certain,” he said.“But I always thought a better under-standing of life’s processes would resultif we knew what made them tick.”

One biological clue to the puzzle wasdiscovered in the 1960s. Heavy water—water made of two atoms of deuterium,the isotope of hydrogen with an extraneutron in its nucleus—could alter theclock to run on a 27-hour day.

“Lots of heavy water was availableback then, as it was needed for nuclearreactors,” he said. “Investigators discov-ered that if you fed cells heavy water,they would operate on a 27-hour day. Itwas a clue that the clock had a bio-chemical basis, but heavy water’s effectwas almost forgotten as other explana-tions for the clock gained favor.”

Forty years passed. Dr. Morré spenttime on other projects, but the biologi-cal clock never escaped his mind orefforts completely. Then an examina-tion of how cells grow led him to thediscovery.

The Morrés found that cells increasein size at a periodic rate – they enlargethemselves for 12 minutes, then rest

for 12 before growing again. The com-plex interaction of proteins is the basisfor many activities within cells, andJames Morré theorized that someundiscovered proteins were responsi-ble for the 24-minute growth cycle.

The discovery came when the teamfound that a single cylinder-shapedprotein molecule with a unique char-acteristic regulated the cell enlarge-ment cycle. This particular protein hadtwo activities: one served as a catalystfor growth activities for 12 minutesand then rested while its other activitytook over for the next 12 minutes.

“Our model is that of a Janus-headprotein with two opposing faces,” hesaid. “One ‘face’ handles cell enlarge-ment. Then the protein ‘flips over,’allowing the second face to carry outother activities while cell enlargementrests. While two functions from a singleprotein had been seen before, what istotally unique here is that these activi-ties alternate, and with very precisetiming. The activities don’t both run allthe time, but instead alternate to gener-ate the 24-minute period length.”

To confirm that the protein wasresponsible not just for regulatinggrowth but for all activities set by thebiological clock, Pin-Ju Chueh, then amicrobiology graduate student in Dr.Dorothy Morré’s lab, isolated the genewhich produced the protein withincells. The team then cloned the pro-tein and altered it in ways that pro-duced different period lengths.

“We found that we could produceclocks with cycles of between 22 and42 minutes,” Dr. James Morré said.“The ‘day’ which the cell experi-enced was precisely 60 times the

he biological clock—time-keeper for virtually everyactivity within living things,

from sleep patterns to respiration—is asingle protein, Purdue Universityresearchers report.

The husband-and-wife team of D.James and Dorothy Morré has discov-ered this protein, which is responsiblefor setting the length of periods ofactivity and inactivity within cells. Ifthe protein is altered, an organism’sbody will experience “days” of differ-ent length—ranging from 22 to 42hours in length in some cases. The dis-covery, they believe, could have far-reaching implications for medicine.

“We can now begin to understandthe complex chain of events that con-nect the clock to events in the body,”said James Morré, an ASBMB memberand Dow Distinguished Professor ofMedicinal Chemistry in Purdue’sSchool of Pharmacy and Pharmacal Sci-ences. “Since the clock affects nearlyevery bodily activity, this discoveryholds myriad potential applications,from minimizing jet lag to determiningwhen best to administer cancer drugs.”

The research is the culmination offour decades of work and a lifelong fas-cination of Dr. James Morré.

“I first set out to find the source ofthe biological clock in 1962, when Iwas still a student,” he said. “Back thenthe question was the subject of peren-nial and lively scientific debate. Theo-ries abounded as to why the body wasable to keep its own rhythm – somethought it was bound up in cellularchemistry, but others thought it couldbe influenced by anything from thelunar cycle to sunspots. No one could

TPurdue Researchers Discover


assist future practical applications ofthe discovery.”

This research was sponsored in part byNASA, the National Institutes of Healthand the Purdue Botanicals Center.

Dr. James Morré is a member of thePurdue Cancer Center, one of eightNational Cancer Institute-designatedbasic-research cancer centers in theUnited States. Established in 1976, thecenter is committed to helping cancerpatients by identifying new moleculartargets and designing future agentsand drugs for effectively detecting andtreating cancer.

Both Morrés are members of the Pur-due-UAB Botanicals Center, which incollaboration with the University ofAlabama-Birmingham, promotes inter-disciplinary botanicals research for theprevention of age-related diseases. Thecenter has received support from theNational Institutes of Health to studycompounds in botanicals purported toreduce the risk of cancer, osteoporosis,cardiovascular disease, cognitive func-tion and other age-related diseases. ThePurdue-UAB Botanicals Center is one offour NIH-funded Botanicals ResearchCenters in the United States.

period length of the protein’s cycle.We even found that feeding cellsheavy water gave them a 27-minutecycle of growth and rest, so that oldpiece of information served to con-firm our theory.”

He said the discovery could be appliedto a great number of biological issues.

“Now we have an opportunity to tellhow organisms tell time,” saidDorothy Morré, an ASNS member andProfessor of Foods and Nutrition inPurdue’s School of Consumer andFamily Sciences. “This could give usnew insights into cellular activity, suchas cholesterol synthesis, respiration,heart rhythms, response to drugs,sleep, alertness—there’s so much.”

While it is presently difficult to makethe biological clock speed up or slowdown, it can be reset, a fact whichcould assist the sleep-deprived.

“This discovery also affords anopportunity to improve our methodsof clock setting, from minimizing jetlag to correcting sleep disorders,” Dr.James Morré said. “We might even beable to develop simple artificial clock-setting environments to aid astronautsand those living near the Arctic Circle,where day-night cycles are absent forlong periods.”

While the research could be applied tomany disorders, the newly discoveredprotein first needs further attention.

“It is very difficult to look at the pro-tein,” he said. “Usually with unknownproteins you can crystallize them andthen examine them with a high-energy X-ray beam, but this one can’tbe crystallized because it’s constantlymoving. A better picture of the proteinswitching back and forth would greatly

Basis For Biolog ical Clock

M E M B E R S I N T H E N E W S

D. James and Dorothy Morré in a Purdue University laboratory. The husband-and-wife team hasdiscovered a protein that is responsible for setting the length of periods of activity and inactivitywithin cells in the body, acting as a biological clock. The research, which appears in the journal

Biochemistry, is the culmination of four decades of work by James Morré.

Purd

ue N

ews

Serv

ice

Phot

o/D

avid

Um

berg

er


levels also rise and trigger productionof prostaglandins. The prostaglandinsbind to tumor cells and help turn ongenes involved in the generation ofnew blood vessels, helping feed thecells’ rapid growth.

In this study, Dr. Anant and col-leagues looked at events early in thedevelopment of tumors. In any cell’slife, there is a normal cycle of replica-tion and division. First, a close copy ofDNA, called RNA is made, and thatRNA, in turn is translated into pro-teins. These proteins have to be madeat precisely the right time in order forthe cycle to work correctly. It isthought that tight regulation of impor-tant proteins is critical, and interferingwith the strict regulation of these pro-teins even by a few minutes can lead toserious problems such as cancer.

That precise timing is controlled bythe activity of messenger RNA (mRNA).Anant and colleagues explored theinteraction of CUGBP2 with COX-2mRNA in eight types of human cancercells. In all eight, levels of CUGBP2were very low.

“This suggests that an important stepin the development of cancer is turning

down the gene responsible for produc-tion of CUGBP2, thereby reducingCUGBP2 protein levels and allowing thecancer to flourish,” Dr. Anant explains.

The researchers also found thatwhen CUGBP2 attached to mRNAfrom COX-2, cancer cells no longercould make COX-2, and they died.That suggested that CUGBP2 mightplay a central role in tumor cell sur-vival or death.

“CUGBP2 may be one type of masterswitch used by the cell to control otherkey proteins,” says co-author Brian K.Dieckgraefe, M.D., Ph.D., Assistant Pro-fessor of Medicine in the Division ofGastroenterology. “Proteins like COX-2need to be tightly regulated to avoiduncontrolled growth. That may be whyCUGBP2 levels were significantly lowerin every single tumor we studied.”

Dr. Anant, Dr. Dieckgraefe and col-leagues also found that CUGBP2 wasnot toxic to healthy cells. Moreover,when they introduced CUGBP2 intocancer cells at the levels found in nor-mal cells, the cancer cells died.

“When CUGBP2 is introduced, thereare a number of molecular derange-ments that take place in the cancer cellthat make it susceptible to death,” Dr.

esearchers at Washington Uni-versity School of Medicine inSt. Louis have found that a

protein called cytidine uridine guano-sine binding protein-2 (CUGBP2) candestroy several different types of cancercells. When the team inserted the pro-tein into cultured tumor cells, morethan 70 percent self-destructed.

The study appeared in the January17 issue of the journal Molecular Cell.The researchers found that CUGBP2helps regulate production of cyclooxy-genase-2, (COX-2), which is betterknown as a key culprit in arthritis.

“The gene that produces COX-2 isturned on very early in cancer, so therehas been a lot of research to seewhether interfering with it might bean effective therapy,” says principalinvestigator ASBMB member ShrikantAnant, Ph.D., Assistant Professor ofMedicine in the Division of Gastroen-terology and Research Member of theSiteman Cancer Center at WashingtonUniversity School of Medicine andBarnes-Jewish Hospital in St. Louis.

In rheumatoid arthritis, COX-2 con-verts arachidonic acid in the body intoprostaglandins. In cancer cells, COX-2

RResearchers Ident i fy Protein

CUGBP2 inhibition results in decreased levels of radiation-induced apoptosis. Colon cancer cells inculture were transfected with either antisense CUGBP2 specific (A) or scrambled (B)oligonucleotide, and subsequently subjected to 12 Gy g-radiation. Apoptotic cells are shown bygreen fluorescence. Nuclear staining of the cells is shown in blue (inset).

Dr. Shrikant Anant


become a synergistic addition to exist-ing therapies. By augmenting existingchemotherapy with CUGBP2, wemight be able to make traditional ther-apies more effective.”

In addition, the team says COX-2might not be the only protein thatCUGBP2 influences. Broad ranges ofproteins have similar targets, so theybelieve CUGBP2 may have a role inregulating the production of those pro-teins, too.

Anant says. “In the future, it may bepossible to use this protein as a meansof killing tumor cells without harmingnormal cells because normal cellsalready produce significant amounts ofthe protein.”

He already is looking at whether it ispossible to use the protein in animalmodels of cancer to see whether it hasthe same effect in their tumors as it didin human cancer cells in the test tube.If these studies continue to demon-

Researchers at Washington Univer-sity School of Medicine in St. Louishave discovered a new antibiotic pro-tein that appears to kill certain types ofbacteria in the intestine. Their resultsare to be published this month in thejournal Nature Immunology.

“These findings were completelyunexpected,” says Lora V. Hooper,Ph.D., Instructor of Molecular Biologyand Pharmacology. “We initiallythought that this protein might beinvolved in blood vessel formation.What we discovered, though, is that it’sa potent killer of bacteria.”

Dr. Hooper is first author of the study.ASBMB member Jeffrey I. Gordon,M.D., the Dr. Robert J. Glaser Distin-guished University Professor and Headof the Department of Molecular Biologyand Pharmacology, led the study.

The team identified a protein calledangiogenin 4 (Ang4), which belongs toa class of proteins originally believed tobe involved in the development ofblood vessels that supply tumors withnutrients. The group discovered thatAng4 was released by specific cells,

called Paneth cells, located in the intes-tinal lining.

Because Paneth cells are known toassist the immune system in defendingagainst infection, the team examinedAng4 to determine how it interactswith a variety of different microbes.They found that the protein killed cer-tain kinds of gut microbes and con-clude that Ang4 may be part of anarsenal of microbicidal proteinsdeployed by Paneth cells to help keepgut bacteria from getting too close tothe intestinal lining, where they could

cause damage or mount an invasion. Moreover, the researchers were sur-

prised to find production of Ang4 iscontrolled by a bacterium that makesits home in the intestine. The microbe,called Bacteroides thetaiotaomicron, isa prominent member of the mouse andhuman gut microbial community. Thismakes Ang4 unique, as it is the firstexample of a protein antibiotic whoseexpression is controlled by friendlyintestinal bacteria.

“Robert Frost said it best: ‘Goodfences make good neighbors,’” notedDr. Hooper. “Apparently, one of thefunctions of normal gut bacteria is tohelp erect an “electric fence” that pro-tects the internal milieu from microbeswe encounter throughout our lives.”

The group also discovered that othermouse and human angiogenins, whichare produced in other organs, also are ableto combat dangerous microorganisms.

“These findings support the notionthat the angiogenin family of proteinsmay represent a critical component ofthe body’s innate defense system,” Dr.Gordon says. Dr. Jeffrey Gordon

Newly Ident i f ied Gut Protein Kil ls Bacteria

strate that it’s possible to kill cancercells by raising CUGBP2 levels, hebelieves the strategy might be ready forhuman testing in a few years.

Even if raising levels of CUGBP2does not eliminate cancer, theresearchers believe it may help existingtherapies work better.

“Most therapeutic tools we currentlyuse for cancer act by triggering cells toself-destruct,” Dr. Dieckgraefe says. “Soit’s entirely possible that this might

That Kil ls Cancer Cells


who is familiar with the research butnot involved in the study.

For cells to produce protein, DNA isfirst transcribed into pre-messengerRNA. Pre-messenger RNA is a “word-for-word” representation of a DNAsequence in the language of RNA, butfor reasons that remain unclear, pre-messenger RNA molecules containexcess “words” that are removed bysplicing to create mature messengerRNA (mRNA), the templates that cellsuse to make proteins. In many geneticdiseases, gene mutations cause errorsin the RNA splicing process. Improp-erly spliced mRNA molecules lead tothe creation of altered proteins thatcannot perform their duties properly,resulting in disease.

Gene mutations that alter pre-mRNAsplicing frequently cause an importantsegment of the RNA to be skipped orleft out of the mature mRNA. Withthis in mind, Dr. Krainer and colleagueDr. Luca Cartegni looked for ways totell a cell to include a piece of RNAthat is erroneously skipped. They tookinspiration from natural proteins thatguide which segments are includedwhen the cell’s splicing machinery cutsup pre-mRNA and pastes only theimportant bits back together. One endof these guide proteins attaches to thepre-mRNA transcript. The other endrecruits enzymes that carry out theactual cutting and pasting.

Dr. Krainer and Dr. Cartegni attachedthe recruiting portion of the guide pro-tein to a synthetic molecule that can beprogrammed to bind to any piece ofRNA according to its sequence. Theresearchers designed a batch of these

molecules corresponding to a mutantform of the BRCA1 gene implicated inbreast cancer. The designer moleculessuccessfully caused the splicingmachinery to include an importantpiece of BRCA1 mRNA that is usuallyskipped. Thus, the designer moleculescorrected the splicing error, making anormal messenger RNA from a defec-tive pre-messenger RNA transcript.

Next, the scientists turned their newtechnology loose on a mutant form ofthe SMN2 gene which is associatedwith the neurodegenerative diseasespinal muscular atrophy (SMA). Peopleafflicted with SMA generally possessboth a fully defective SMN1 gene andone or more copies of the closelyrelated SMN2 gene which, due to skip-ping of a particular segment duringRNA splicing, is capable of producingonly small amounts of normal mRNA.The severity of SMA symptoms couldbe relieved if a patient’s SMN2 genecould be coaxed into producing morenormal mRNA by including theskipped RNA segment more often. Justas they corrected splicing defects ofBRCA1 RNA, Dr. Krainer and Dr.Cartegni’s designer molecules alsoenhanced the production of properlyspliced SMN2 RNA.

The scientists dubbed the methodESSENCE (Exon-Specific SplicingEnhancement by small Chimeric Effec-tors). The next step is to create ESSENCEdesigner splicing molecules that passeasily into cells and can home in on thedesired splicing targets. If such mole-cules can be developed, they may ulti-mately prove useful for treating a greatdiversity of human disease.

ith a high-tech fix for faultycellular editing, scientists atCold Spring Harbor Labora-

tory have moved a step closer to devel-oping treatments for a host of diseasesas diverse as breast cancer, musculardystrophy, and cystic fibrosis.

Many human diseases have beenlinked to defects in a cellular editingprocess called pre-messenger RNAsplicing. Adrian Krainer, an ASBMBmember and molecular biologist atCold Spring Harbor Laboratory, hasspent years investigating this complexediting process, which takes the infor-mation coded in genes and makes itavailable for building proteins. In anew study, Dr. Krainer’s team hasdevised a clever way to correct RNAsplicing defects implicated in breastcancer and spinal muscular atrophy (aneurodegenerative disease). In princi-ple, the technique could provide theability to correct RNA splicing defectsassociated with any gene or disease.

For now, Dr. Krainer’s method hasbeen shown to work under the sim-plest of conditions — in test tubes withsmall segments of RNA. The next stepis to adapt the technique for use in liv-ing cells. “It’s a very promisingapproach,” according to molecularbiologist Brenton Graveley, of the Uni-versity of Connecticut Health Center.“There are a lot of hurdles to be over-come in terms of delivering the correc-tive molecules to the cells that need tobe treated. But theoretically the exactsame approach could be taken for anygene at all, and the list of genes thathave defects at the level of RNA splic-ing is very long,” said Dr. Graveley,

W

Designer Molecules MayCorrect R NA Splicing Defects


2001-2002conferred and the increase in doctor-ates is possibly due to the type ofinstitutions responding to the survey.Most of the institutions respondinghad a student population of less than5,000, but this includes medicalschools which often have smallenrollments.

At both the bachelors and masterslevel, degrees awarded in 2001-2002were down for all minorities, while atthe Ph.D. level all categories were upfrom the preceding year. For 2001-2002 the number of minorities receiv-ing bachelors was 459, down from 654in 2000-2001; for masters it was 68,down from 96; but the 2001-2002 sur-vey found 127 minority candidatesreceiving doctorates compared to 78 inthe preceding year

he 2001-2002 ASBMB Gradua-tion Survey found a decreasein the number of bachelors

and masters degrees awarded whiledoctorates awarded were up substan-tially from the 2000-2001 GraduationSurvey. The survey was sent to a totalof 448 departments known to offerdegrees in biochemistry, molecularbiology, or chemistry with a biochem-istry emphasis, and 223 responded, up16% from the 192 in the previous year.

The schools responding reportedawarding 1,985 bachelors and 296masters degrees, and 650 doctoratesbetween July 1, 2001 and June 30,2002. The corresponding numbers for2000-2001 were 2,036 bachelors, 341masters, and 450 doctorates. Thedecrease in bachelors and masters

Graduat ion Survey ResultsT

Students Graduated, July 1, 2001—June 30, 2002Bache lors Masters Doctora l

M F Total M F Total M F Total

American Indian or Alaskan Native 5 5 10 0 2 2 0 0 0

Asian 111 148 25 19 25 44 45 33 78

Black, not of Hispanic origin 29 48 77 3 6 9 6 7 13

Hispanic 39 55 94 6 6 12 9 11 20

Pacific Islander 8 11 19 0 1 1 6 10 16

White, not of Hispanic Origin 732 683 1415 100 78 178 215 133 348

International Students 49 62 111 23 27 50 104 71 175

Total 973 1012 1985 151 145 296 385 265 650

These graduation surveys are onlyas representative as the responsesfrom departments. To see if yourschool responded to the survey, see the list of respondents at in thesurvey section of education athttp://www.asbmb.org/. The schoolsthat we know offer degrees at somelevel can also be seen in the educa-tion section of the website.

If you know of any schools thatoffer a degree in biochemistry,molecular biology, or chemistry with a biochemistry emphasis, please contact Kelly Gull [email protected]. With yourassistance we can contact moreschools and have an even moredefinitive 2002-2003 survey.


to invasion by foreign organisms or totrauma. Uncontrolled inflammationcan cause extensive cell damage andeven death. Better understanding ofproteins involved in the initiation andcontrol of inflammation could helpscientists find targets for new drugsthat can precisely modify the inflam-matory response.

NIAID also recently awarded twocontracts to support research in a keyarea of systems biology?bioinformat-ics?the computational analysis andorganization of biological data such asgene sequences and protein structure.The contract awardees, Research Trian-gle Institute in Research Triangle Park,

North Carolina, and Northrop Grum-man in Herndon, Virginia, will assessthe bioinformatics needs of scientistsworking in such areas as transplantbiology and autoimmune diseases. Thecontractors will also develop and test aprototype system that reliably and sim-ply collects, stores and analyzes manyforms of biological data generated bymultiple laboratories.

“The new grant, along with thesenew bioinformatics contracts, signalsNIAID’s interest in advancing bioinfor-matics resources to support both basicand clinical research on immune-mediated diseases,” NIAID’s Dr.Rotrosen said.

teins generated and biochemical path-ways triggered by encounters betweeninnate immune system cells and infec-tious agents. Unlike the highly specific

antibodies, whichare produced inalmost infinitevariety and whichmatch a particulardisease organismlike a key in alock, cells of theinnate immunesystem react

generically to a wide range of sub-stances, including molecules found inthe cell walls of many kinds of bacteria.

An encyclopedic account of thesecomplex and interwoven processesrequires a systems biology approach,says Dr. Ulevitch. Dubbed “21st-cen-tury biology,” this relatively new fieldof systems biology melds mathematics,computer modeling, and new tech-niques of gene and protein analysis inan effort to gain a wide-angle view ofbiological systems.

Systems biology assembles informa-tion about many genes, proteins andbiochemical reactions at once withoutregard for function. These enormousamounts of data are then integratedand examined from multiple perspec-tives to learn how the system as awhole behaves.

Scientists at TSRI, ISB and Rocke-feller University will focus on humaninnate immune system genes that areturned either off or on when a cellmeets an infectious organism. Due tothe high degree of similarity in theinnate immune systems in all animals,the scientists can employ mice toquickly determine which gene groupsdeserve further exploration. Both thehuman and mouse genes, for exam-ple, encode proteins involved ininflammation, a generic first response

comprehensive and detailedpicture of innate immunity—the human body’s first line of

defense against disease—is the goal ofscientists funded by a recently awardedfive-year, $24-million grant from theNational Institute of Allergy and Infec-tious Diseases (NIAID).

Researchers at The Scripps ResearchInstitute (TSRI) in La Jolla, California,the Institute for Systems Biology (ISB)in Seattle, and Rockefeller University inNew York are using techniques thatstraddle the divide between biologyand information science to fathom theworkings of innate immunity. Knowl-edge generated could help scientistsdevelop treatments for septic shock,certain autoimmune disorders and dis-eases caused by potential agents ofbioterrorism.

Daniel Rotrosen, M.D., Director ofNIAID’s Division of Allergy, Immunol-ogy and Transplantation, notes, “Thecollaborators at TSRI, ISB and Rocke-feller University have complementaryexpertise that is most impressive.”

“Our goal is to develop an encyclo-pedia of innate immune system activ-ity,” says ASBMB member Richard J.Ulevitch, Professor and Chair of TSRI’sImmunology Department and the pro-ject’s principal investigator.

Innate immunity is inborn and pro-vides an all-purpose defense againstinvasion. Innate immune system cells,including certain skin cells calledLangerhans cells, arrive soon after for-eign elements are detected. Some sys-tem components, called macrophages,find and engulf microorganisms, whileothers release chemicals that kill theorganism directly. Still other cells beginrecruiting specialized immune cells tothe region.

Dr. Ulevitch and his co-investigatorsface the daunting task of identifyingthe thousands of genetic changes, pro-

APowerful Technolog ies Wil l Probe Innate Immunity

Dr. Richard Ulevitch

D u b b e d “ 2 1 s t - c e n t u r y

b i o l o g y, ” t h i s

r e l a t i v e l y n e w f i e l d

o f s y s t e m s b i o l o g y

m e l d s m a t h e m a t i c s ,

c o m p u t e r m o d e l i n g ,

a n d n e w t e c h n i q u e s

o f g e n e a n d p ro t e i n

a n a l y s i s .


Gannon, EMBO Executive DirectorUnder the agreement, both EMBO

and CAS, will encourage researchersfrom China and Europe to enter intoor intensify scientific collaborationswith each other in the field of life sci-ences. To ensure that such co-opera-tion will be beneficial to thedevelopment of science in Europe andChina, the two organizations will iden-tify priority areas for mutual aid with aview to establishing at least one largeresearch project.

“The Chinese Academy of Sciences,the highest organization of natural sci-ences in China and a major player inthe Chinese scientific community ispleased to see the signing of this agree-ment. It will open new possibilities for

Chinese-European co-operation. Thisholds especially true for young life sci-entists on both sides,” said Chen Zhu,Vice President of the Chinese Academyof Sciences.

Last year EMBO added a medium-term fellowship scheme directed at sci-entists from emerging economies to itsportfolio. As part of the new agree-ment, two such fellowships will beawarded to young Chinese scientistsfrom CAS laboratories. This will allowChinese life science researchers to visitEuropean laboratories for six to ninemonth periods. In return, the ChineseAcademy of Sciences has agreed tofund visits of young Europeanresearchers to Chinese laboratories fortwo weeks to six months.

he European Molecular Biol-ogy Organization (EMBO) andthe Chinese Academy of Sci-

ences (CAS) have signed an agreementto enhance collaboration with eachother over the next two years. The firstcooperative agreement with another sci-entific organization that EMBO hassigned during its 40 years of existence, itis designed to support life scienceresearchers from China and Europethrough fellowships and joint meetings.

“The significance of this agreement istwo-fold. First of all, it consolidates ourworking relationship with the Chinesescientific community and secondly, itshows that EMBO is actively buildinglinks with scientific organizationsthroughout the world,” said Frank

E M BO and Chinese Academy of SciencesJoin Efforts in Life SciencesT

Is your Directory listing correct?Update your online record anytime during the year.

To update your online listing in the FASEBDirectory of Members, visit www.faseb.org andclick on Member Directory at the left or godirectly to http://12.17.12.70/fasebdir

Click Update Member Info at the top of yourscreen to make changes.

Please note: There is a time delay between submittingrevisions and their actual appearance online.

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


by John D . Thompson , Ed i tor

Rancho Cordova, California-basedThermoGenesis Corp. recently receivedits fourth BioArchive order from Taiwan.The system was ordered by the com-pany’s distributor, Cosmo Medical, forTaiwan Advance Biopharmaceutical,which now joins Healthbanks and theTzu-Chi Foundation Cord Blood Bank asthe third cord blood stem cell bank inTaiwan using the BioArchive System fortheir cord blood program. Four moresuch blood banks in mainland Chinahave also acquired these systems for theproduction of therapeutic units of cordblood stem cells for the treatment ofleukemias, lymphomas, diverse inherited

anemias, such as sickle cell anemia andthalassemia, and other genetic diseases.

Kevin Simpson, ThermoGenesisPresident and COO, noted that inmainland China a new stem cell proj-ect was planning to inventory of onemillion samples, and predicted contin-ued demand for BioArchive in Asia,which he said have been under-servedby traditional U.S. and European bonemarrow registries. “Cord blood,” hestated, “serves as a readily availablesource of stem cells for bone marrowrescue treatment, especially for diseasessuch as thalassemia, which occurs atan incredibly high rate in Asia.”

“Leader of a top research institute,cofounder of a pioneering biotechnologycompany, Bill Rutter is that rare combina-tion of entrepreneurial spirit and high-level management skills so important tothe rapid growth of biotechnology bothas a discipline and as a global industry,”said Arnold Thackray, President of CHF.

In 1969, Dr. Rutter joined the facultyof UCSF as Hertzstein Professor andserved as Chairman of the Departmentof Biochemistry and Biophysics from1969 to 1982. FromAugust 1983 throughApril 1989, he was Direc-tor of the HormoneResearch Institute atUCSF. He became a Pro-fessor Emeritus in 1991.

The Biotechnology Her-itage Award recognizesindividuals who havemade significant contributions to thedevelopment of biotechnology throughdiscovery, innovation, and public under-

standing. Nobel Laureates Walter Gilbertand Phillip A. Sharp, both ASBMB mem-bers, were honored in 2002 for foundingBiogen, a pioneer company in biotech-nology. Francis S. Collins, Director of theNational Human Genome ResearchInstitute, and J. Craig Venter, formerPresident of Celera Genomics, receivedthe award in 2001 for their key roles inthe sequencing of the human genome.

CHF, a not-for-profit organization,operates a historical research library;

creates and circulates trav-eling exhibits; developsand disseminates educa-tional materials; publishesbooks and Chemical Her-itage newsmagazine; offersfellowships and travelgrants; conducts oral his-tories with leading scien-tists and industrialists; and

hosts awards, conferences, and publicevents. For more information, visitwww.chemheritage.org.

The Chemical Heritage Foundation(CHF) and the Biotechnology IndustryOrganization (BIO) will present the 2003Biotechnology Heritage Award toASBMB member Dr. William J. Rutter. Abiotechnology pioneer, Dr. Ruttercofounded Chiron Corporation in 1981and directed the Hormone ResearchInstitute at the University of California,San Francisco (UCSF), for nearly adecade. The award will be presented atthe BIO 2003 Annual Convention, June22-25, at the Washington, D.C., Con-vention Center.

AS BM B Member to Receive Biotechnology Heritage Award

Taiwan Stem Cell Banks Embrace U.S. Technology

Human GenomeSciences OpensEuropean Off ice

Human Genome Sciences Inc.has opened a new European sub-sidiary in Düsseldorf, Germany.

The new subsidiary, HumanGenome Sciences Europe GmbH,will be responsible for Europeanclinical trials of the company’s port-folio of new drugs in clinical andlate-stage pre-clinical development,the Rockville, Maryland, companysaid in a statement.

Florian Bieber, former head of thecardiovascular, metabolic disordersand central nervous system thera-peutic areas at Bayer AG, has joinedthe company as Vice President ofDrug Development Europe, HumanGenome Sciences said. He will workwith David Stump, Senior Vice Presi-dent Drug Development, to managethe group’s clinical trials and clinicalresearch collaborations in Europe.

Biotech Pioneer William Rutter


Avant to DevelopOral Anthrax andPlague Vaccine forDefense Department

The Defense Department hasawarded Avant Immunotherapeu-tics, Inc. a subcontract to developan oral combination vaccineagainst anthrax and plague usingAvant’s proprietary vaccine tech-nologies. Under the agreement,Avant may receive over $8 millionin a two-year period, covering vac-cine development through pre-clinical testing. Avant executedthe subcontract with DynPort Vac-cine Company LLC, the primecontractor for the Defense Depart-ment’s Joint Vaccine AcquisitionProgram headquartered in FortDetrick, Maryland.

“This contract represents one ofthe first awards from a major U.S.Department of Defense (DoD) ini-tiative to apply modern biotech-nological innovations to thedevelopment of vaccines that canoffer rapid, effective protectionfrom multiple biological agents,”said Una S. Ryan, Avant’s Presi-dent and CEO. “Current vaccinesagainst bacterial bioweapons likeanthrax and plague require a pro-tracted dosing regimen or onlylimited protection, and each pro-tects against only a single agent.The Defense Department is look-ing for new, improved generationvaccines that are effective, single-dose, and can protect againstmultiple agents.

Takeda Chemical Industries, LTD,and Beth Israel Deaconess Medical Cen-ter (BIDMC) have signed a researchagreement to investigate the molecularbasis of diabetes and obesity and todevelop new therapies for these meta-bolic diseases. The $13.7 million three-year agreement calls for collaborationbetween Takeda and a team of scien-tists led by BIDMC Chief AcademicOfficer Jeffrey S. Flier. Principal investi-gators include BIDMC Chief ofEndocrinology Barbara Kahn, anASBMB member; Dr. Bradford Lowell,Dr. Joel Elmquist, and BIDMC Chief ofthe Division of Signal TransductionLewis Cantley, also an ASBMB member.

Takeda Chemical Industries, anindustry leader in the development ofdiabetes therapies, is Japan’s largestpharmaceutical firm and one of the 15largest pharmaceutical companiesworldwide. More than 1,000researchers at Takeda carry out world-

class research using advanced technol-ogy in such fields as human genetics,receptors, and enzymes.

Under the terms of the three-yearagreement, Takeda Chemical Indus-tries will have an exclusive option tonegotiate a license to new intellectualproperty derived from the collabora-tion. BIDMC and Takeda researcherswill collaborate on a number of spe-cific projects designed to elucidate thebiological mechanisms of diabetes andobesity, with the overall goal of dis-covering novel proteins and new drugtargets implicated in these life-threat-ening diseases.

As part of the collaboration,BIDMC will gain access to Takeda’sexpertise in medicinal chemistry anddrug discovery as well as resources todevelop important core facilities atBIDMC including animal metabolicphysiology, mass spectrometry, andproteomics.

Takeda Chemical and Be th IsraelDeaconess Sign Research Agreement

Businesses receiving support from theGerman Ministry of Education andResearch invest more than one euro inresearch and development for every eurothey receive from the ministry. This wasthe finding of a study, Public Support forResearch and Iinnovation Activities of Busi-nesses in Germany, conducted by the Cen-tre for European Economic Research forthe Ministry of Education and Research.One in six industrial companies receivespublic funding for research and innova-tion in Germany and a third of these par-ticipate in national research programmes.

The study of businesses which hadreceived funding for basic researchand high risk projects. found thatthose receiving government fundsown more patents and are signifi-cantly more successful in getting theirproducts onto the market. It alsodetermined that more funding nowtargets collaborative projects than pre-viously. While such projects were theexception 20 years ago, two thirds offunding now goes to collaborativeprojects, almost half of them public-private partnerships.

Public R&D Funding Pays Off in Germany

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


good ones to use as seeds in a conceptsearch, though. But, perhaps best, a sim-ple keyword search on the word “pro-teasome” retrieves “only” about 12,000items. Let’s start with this last result asthe seed for searching by concept.

Notice the blue, right-most column ofthe search result page shown here – youcan narrow or widen your browser win-dow depending on whether you wantto see the topics or not. Here we see aselection of the topics that each articleis filed under. We’re going to check theboxes for the topics that match the con-cepts we’re interested in: Ubiquitin, Pro-tein Degradation, and Proteasomes.

Then click on the Search buttontoward the top of this right most col-umn. First choose options for ALL top-ics (meaning that each article in thenew result must contain all threechecked topics) and Within CurrentResult (meaning that our keywordsearch result on “proteasome” will bereduced, refined and limited to thethree topics we’ve chosen.

The new result is “only” 233 articles,but each of these articles has somethingto say about all of these three topics.

Notice that the first article is a review

article covering these topics. With the“one click” options described in an ear-lier article in this series, you can quicklylimit the result to review articles only, orto the top-ranked HighWire-hosted arti-cles (for which full text is likely to be

online), or sort the results so thatthe newest articles are first. Youcan even further narrow yourtopic search by checkmarkingmore topics and clicking theSearch button again.

The L im itat ionsof ConceptSearch ing

Concept search is a good way to“find what you are missing” whenyou have been relying on themore traditional author and key-word searches. It is good to pair italongside other exploration toolslike Citation Map and InstantIndex (both described in previous

articles in this series), and MatchMaker(described in an upcoming article).

You should not use concept searchas your only tool when you need toconduct an exhaustive review of atopic. While the “taxonomy” of con-cepts is extensive?we have indexedalmost 30,000 concepts?and was devel-oped and tested by working scientistsand editors using a real-world scientificand medical vocabulary, the actualassignment of individual articles tospecific topics is done by computerprograms. (The programs analyze textin articles and extract concepts bylooking for frequent phrases thatmatch the phrases that editors havesaid are associated with the topics.)The computer assignment is generallyvery reliable, but not perfect: a fewtopic assignments are made thatshouldn’t be, and a few are not madethat should be. We’re sure you’ll spotsome of each!

earching for an article that isabout several topics in combi-nation is one of the hardest

things to do in most keyword-searchsystems. And when you search on akeyword and find that it describes astro-nomical features as well as biologicalones (e.g., “mercury”) you would like tobe able to select only the portion ofyour result that has to do with yourtopic. It just got easier to do these thingswith the HighWire Portal’s new conceptsearch feature, called Topic Search.

How Concept SearchWorks : Start w ith aKeyword as a “Seed”

Searching for topics can be hit ormiss in some systems. After all, how doyou know what concepts or topics tosearch for? In the HighWire Portal youstart a topic search with a keywordsearch that will find some of the articlesyou’d like: whenever you do a key-word search, your search results showyou what topics the resulting articlesare indexed under. You can then easilyuse the topics shown, individually orin combination, in a topic search withjust a few clicks. You can subset yourkeyword search to retain only articlesabout certain concepts, or you canstart a new search based entirely oncombinations of concepts in an article.

Example : ConceptSearch at Work

Suppose you are interested in ubiqui-tin-mediated degradation by the protea-some. You begin a concept search byplanting a seed: you could do a key-word search for articles that have all thewords “ubiquitin-mediated degradationby the proteasome”; zero result is notsurprising. But a keyword search for anyof those words finds almost 5 millionitems! The top items in the result –thanks to “relevance ranking” —are

S

Concept Search:Cutt ing Large Keyword Searches down to Size

Figure 1


From our site you canrenew your membershipor, if you are not already amember, join the Society.You can also register forASBMB-sponsored meet-ings and read our maga-zine, ASBMB Today, ordownload a PDF of it.

Our goal is to make thesite a valuable resource.Giving the content man-agers the ability to keepthe site up to date makesthe information moreaccurate and relevant. Wesee the site as a dynamicresource for communicating with themembership, and this update bring us

closer to that goal. (Information by Sys-tem Coordinator Hector Martinez.)

SBMB’s website now has anew, more up-to-date look.and greatly improved naviga-

tion. We added a “What’s New” sectionto our home page, so you can get to thelatest Society news in one click of themouse. The home page also containsgraphic links to all of our publications.Once you are past the home page, youwill realize that we have made navigat-ing the site a lot easier. On each of pageyou will find two menu bars right underour logo. The first one allows you tomove back and forth between the mainareas, a second menu bar below the firstone shows the submenu for the selectedarea. This way, you always know whereyou are and can quickly get to the infor-mation you need.

Check Our New WebsiteA

Education in the Molecular Life Sciences: The Central Role of Biochemistry and Molecular

Biology Satellite MeetingJuly 18-20, 2003*

University of Toronto, Canada

Organized by: J. Ellis Bell, University of Richmond and Jeanne Narum, PKAL

Sponsored by the ASBMB, IUBMB and Project Kaleidoscope

New Teaching PedagogiesComputational Approaches for Use in Education of Biochemists and Molecular BiologistsTeaching Biotechnology Around the WorldDesigning Curricula that Work for Students: Undergraduate, Ph.D and M.D.The Central Role of Quantitative Skills in Biochemistry and Molecular BiologyPlans for Assessing the Impact of Innovation in Education

*To be held immediately prior to International Congress of Biochemistry and Molecular Biology, July 20-24, 2003, Toronto IUBMB Congress website: http://www.iubmb2003.org

For further information contact:Dr. Ellis Bell: [email protected] or the

ASBMB, 9650 Rockville Pike, Bethesda, MD 20814Tel: 301-634-7145; Fax: 301-634-7126; Email: [email protected]

Meeting website: http://www.richmond.edu/~jbell2/iubmb-satellite.html

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


ECM IV: Bone Tissue Engineering

June 30-July 2 • Davos, SwitzerlandContact: R. Geoff Richards, Dr. Sci. M.Sc. biol.Programme Leader AO Research Institute, Bioperformance of Materials & Devicesemail: [email protected]; Ph: ++41 (0) 81 4142 397http://www.aofoundation.org/events/ao/ecm/ECMIV/index.shtml

J U LY 2 0 0 3

FEBS 2003 Meeting on Signal Transduction

July 4-8 • BrusselsContact: V. Wouters; Ph: 32 2 7795959; Fx: 32 2 7795960Email: [email protected]; Website: http://www.febs-signal.be

Education in the Molecular Life Sciences: The CentralRole of Biochemistry and Molecular Biology

July 18-20 • University of Toronto, CanadaContact: Kelly Gull; Ph: 301-634-7145; Fx: 301-634-7126Email: [email protected]://www.richmond.edu/~jbell2/iubmb-satellite.html

19th International Congress of Biochemistry andMolecular Biology

July 20-24 • Toronto, CanadaContact: Congress Secretariat; Ph: 613-993-9431Email: [email protected]: http://www.nrc.ca/confserv/iubmb2003/

A U G U S T 2 0 0 3

First Gordon Research Conference on CellularOsmoregulation: Sensors, Transducers and Regulators

August 15–20 • Roger Williams University, Bristol, RI Contacts: Janet M. Wood ([email protected]) and KarlheinzAltendorf ([email protected]) Website: http://www.grc.uri.edu/programs/2003/cellosmo.htmApplication: http://www.grc.org/scripts/dbml.exe?Template=/Application/apply1.dbm

Sixth International Symposium on Mass Spectrometryin the Health and Life Sciences: Molecular and CellularProteomics

August 24-28 • Fairmont Hotel, San FranciscoContact: Marilyn Schwartz; Ph: 415-476-4893Email: [email protected]: http://donatello.ucsf.edu/symposium

Biology of Molecular ChaperonesMechanisms and Regulation of Chaperones

August 30–September 4 • Tomar, PortugalContacts: Dr. Josip Hendekovic or Caroline WalfordPh: + 33 388 76 71 35; Fx: + 33 388 36 69 87 Website: http://www.esf.org/esf_eurescoPlease quote 2003-15 in any correspondence

A P R I L 2 0 0 3

Origin and Evolution of Mitochondria and ChloroplastsAdvanced Lecture Course for the Federation ofEuropean Biochemical Societies (FEBS)

April 5–10 • Hvar, CroatiaContact: Prof. Dr. Jürgen SollPh: + 49 89 17861 225/273/276; Fx: + 49 89 17861 185e-mail: [email protected]: http://www.febs.unibe.ch/Activities/Advanced_Courses/Adoc03.htm

9th International Congress on Neuronal CeroidLipofuscinosis (Batten Disease)

April 9-13 • The Holiday Inn-City Centre, Chicago Program Chair: Glyn Dawson, University of Chicago PritzkerSchool of Medicine; Website: http://www.ncl2003.org/

American Society for Biochemistry and MolecularBiology Annual Meeting in Conjunction with EB2003April 11-15 • San Diego, CaliforniaContact: EB2003 Office; Ph: 301-634-7010Fx: 301-634-7014; Email: [email protected]: http://www.faseb.org/meetings/eb2003

9th National Symposium on Basic Aspects of Vaccines

April 30–May 2 • Bethesda, MarylandContact: Conference Secretariat; Walter Reed Army Institute ofResearch; Dept of Membrane Biochemistry503 Robert Grant Ave, Room 2A24; Silver Spring, MD 20910Ph: 301-319-9462 fx: 301-319-9035e-mail: [email protected]: http://wrair-www.army.mil/symposia/dmbsym.htm

M A Y 2 0 0 3

Proteomic Solutions in Cellular and DevelopmentalBiology and Medicine

May 2–4 • Stowers Institute, Kansas City, MissouriContact: Kelly Gull; Ph: 301-634-7145; Fx: 301-634-7126Email: [email protected]; Website: http://www.asbmb.org

10th Undergraduate Microbiology EducationConferenceMay 16-18 • University of Maryland, College Park, MarylandContact: Carlos Pelham; Ph: 202-942-9317Email: [email protected]: http://www.asmusa.org/edusrc/edu4c.htm

J U N E 2 0 0 3

Transposition, Recombination and Applications toPlant Genomics A Plant Sciences Institute Symposium

June 5-8 • Iowa State University, Ames, IowaContact: Gulshan SinghPh: 515-294-7978; Fx: 515-294-2244; E-mail:[email protected]: http://molebio.iastate.edu/-gfst/phomepg.html

ASBMB dues notices have been mailed to all members and you can now makepayment online at the ASBMB website:www.asbmb.org. Click on “Renew Now”in the “What’s New” box.

New for 2003 — Membership CardsThe renewal notice includes your newASBMB membership card. And don’tforget, your membership includes a free subscription to our monthly magazine, ASBMB Today, plus freesubscriptions to JBC Online and MCPOnline. You also receive special memberrates for Biochemistry and MolecularBiology Education, The Journal of LipidResearch and Trends in BiochemicalSciences, as well as the print versions of JBC and MCP.

ASBMB members may also register forthe Annual Meeting at discounted rates.In addition, you can order your 2003edition of the Annual Review ofBiochemistry through ASBMB.

If you have any questions, pleaseemail [email protected].

Renew Your 2003Membership Online

16th International Mass Spectrometry SocietyConferenceAugust 31–September 5 • Edinburgh, Scotland, United KingdomContact: John Monaghan; Email: [email protected]: http://www.imsc-edinburgh2003.com

S E P T E M B E R 2 0 0 3

NMR in Molecular Biology EuroConference on Structural Genomics: From Gene toStructure as viewed by NMR

September 5–10 • Obernai (near Strasbourg), FranceContact: Dr. Josip Hendekovic or Anne-Sophie GablinPh: + 33 388 76 71 35; Fx: + 33 388 36 69 87Website: http://www.esf.org/esf_eurescoPlease quote 2003-14 in any correspondence

Sixth Conference on Protein Expression in Animal Cells

September 7–11 • Mont-Tremblant, QC, Canada Contact: Marc Aucoin, Technical Officer Biotechnology Research Institute; Email: [email protected]: http://www.bri.nrc.ca/6thPEACe

Third International Conference on the Pathobiology ofProteoglycans

September 20 - 25 • Parma, ItalyContacts: Roberto Perris, Chair and Ariane De Agostini, Co-chairClinique de Stérilité de d’Endocrinologie gynécologique,Hôpital Cantonal Universitaire de GenèvePh: 41-22 / 382.43.46; Fx: 41-22 / 347.59.79Email: [email protected]: http://www.assb.biol.unipr.it/PG2003

O C T O B E R 2 0 0 3

OARSI’s 2003 World Congress on Osteoarthritis

October 12-15 • Palais am Funkturm, BerlinContact: OARSI Headquarters; Ph: 202-367-1177; Fx: 202-367-2177Email: [email protected]; Website: www.oarsi.org

Cytokines, Signalling & Diseases

Oct. 26-30 • Cairns, AustraliaEvent Host: International Society for Interferon and CytokineResearch; Website: http://www.cytokines2003.conf.au/

J U N E 2 0 0 4

American Society for Biochemistry and MolecularBiology Annual Meeting and 8th IUBMB Conference

June 12-16 • Boston, MassachusettsContact: Kelly Gull; Ph: 301-634-7145; Fx: 301-634-7126Email: [email protected]; Website:http://www.asbmb.org/meetings

Molecular & Cellular

PROTEOMICSSubscriptions - Institutions and Non-membersPrint Only.......................................................................$350.00Online Only....................................................................$600.00Print + Online.................................................................$950.00

Subscriptions - ASBMB MembersPrint .................................................................................$75.00Online ...............................................................................FREE

All prices are in U.S. Dollars.MCP is a calendar year subscription with 12 issues.Shipping for MCP printed version to non-U.S. addressesadd: $36.

Molecular and Cellular Proteomics (ISSN 1535-9476) and MCPOn-Line are published monthly by The American Society forBiochemistry and Molecular Biology, Inc., 9650 Rockville Pike,Bethesda, MD 20814, USA.

Institutional/non-member print subscribers send payment to theaddress below. All institutional payments should be made payableto Molecular and Cellular Proteomics. ASBMB members canorder when renewing member dues or by contacting the ASBMBmembership office at [email protected]

Single copies of MCP may be purchased for $30 each. Non-U.S.A. orders must add $5 shipping. Prepayment isrequired. Send payment with your request including Volume and Issue, Date of Publication, Journal Title, and mailing address to:

Molecular and Cellular ProteomicsP.O. Box 830399Birmingham, AL 35283-0399, USATel: 1-800-633-4931 or 205-995-1567

Tel: 301-634-7140 Fax: 301-634-7108E-mail: [email protected]

See www.mcponline.org/subscriptions for more information.

Molecular & Cellular

PROTEOMICS

Constituent Society of FASEB AMERICAN SOCIETY FOR ......4 The Welch Foundation: Devoted to Chemistry...

Documents

Transcript of Constituent Society of FASEB AMERICAN SOCIETY FOR ......4 The Welch Foundation: Devoted to Chemistry...