LEHMAN AND ALLIS TO RECEIVE 2008 ASBMB AWARDS
November 2007
Capecchi Awarded Nobel Prize in Medicine
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ON THE COVER: ASBMB Member Mario R. Capecchi society news has been awarded the 2008 Nobel Prize in Physiology or 2 President’s Message Medicine for his pioneering work in gene targeting in mice. 3 Washington Update 8 8 Mario R. Capecchi Receives Nobel Prize in Physiology or Medicine special interest NIH Spending on Training Grants and Fellowships 10 Trends in Postdoctoral Training 900,000 5.00
800,000 4.50
700,000 4.00 3.50 2008 meeting overview 600,000 3.00 500,000 2.50
DOLLARS 400,000 2.00 14 The 2008 Herbert Tabor/ 300,000 1.50
Journal of Biological Chemistry 200,000 1.00 Lectureship: I. Robert Lehman 100,000 0.50 0 0.00 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 2005 2007 15 The 2008 ASBMB Merck YEAR Award: C. David Allis Dollars Percent of total NIH Budget science focus 10 28 Bonnie Bassler: Understanding How Bacteria Communicate departments 4 News from the Hill 6 Member Spotlight 16 Minority Affairs 20 Career Insights 22 Education and Training 24 Industry Perspective 26 BioBits resources at the 2006 SSCACNA SCS Conference. 31 For Your Lab 16 32 Career Opportunities 36 Scientific Meeting Calendar 26
November 2007 ASBMB Today 1 firstsecondpresident’s words message A monthly publication of The American Society for Biochemistry and Molecular Biology Great Session Officers Heidi E. Hamm President Planned for Grad Gregory A. Petsko President-Elect Mark A. Lemmon Secretary Students and Merle S. Olson Treasurer Council Members Postdocs at Alan Hall Kuan-Teh Jeang Suzanne R. Pfeffer Linda J. Pike Annual Meeting John D. Scott Joan A. Steitz Kevin Struhl James A. Wells BY HEIDI HAMM Ex-Officio Members Ellis Bell Chair, Education and Professional Development Committee Laurie S. Kaguni hile public policy is obviously and discussion session on career Chair, Meeting Committee Wa major interest of mine (as options, featuring speakers from the George Hill those of you who read my columns areas of patent law, science writing, Chair, Minority Affairs Committee Kendall J. Blumer here know) I am also an educator industry consulting, and more. Anna Marie Pyle and a researcher. Thus, I’m happy to A group networking lunch will be Co-chairs, 2008 Program Committee write this month about another sub- followed by short oral talks presented Mary J. C. Hendrix Chair, Public Affairs Advisory Committee ject dear to my heart—graduate and by select Graduate Minority and Robert E. Rhoads postdoctoral professional develop- Graduate/Postdoctoral Travel Award Chair, Publications Committee ment and the exciting program the recipients. Herbert Tabor Editor, JBC Society has created for the annual Afternoon workshops will high- Ralph A. Bradshaw meeting in San Diego next April. light topics including: Lab Produc- A. L. Burlingame The Graduate and Postdoctoral tivity/Lab Management, Matching Co-editors, MCP Edward A. Dennis Professional Development Program Yourself with a Mentor, Pinpointing Editor, JLR has been put together by: the Perfect Postdoc, and Making the Most of Your Postdoc Experience. ASBMB Today t,JNCFSMZ%PEHF,BėB 6OJWFSTJUZ Editorial Advisory Board PG $POOFDUJDVU )FBMUI $FOUFS JO Following these career development Alex Toker 'BSNJOHUPO workshops, program attendees will Chair join the main meeting at The Herbert Mike Autry Greg P. Bertenshaw t+PIO . %FOV 6OJWFSTJUZ PG Craig E. Cameron A. Stephen Dahms 8JTDPOTJO .FEJDBM 4DIPPM Tabor/Journal of Biological Chemistry Irwin Fridovich Richard W. Hanson Lectureship, featuring I. Robert Leh- Elizabeth A. Komives t "OO - .JMMFS 6OJWFSTJUZ PG man of Stanford University. Bettie Sue Masters Luke A. O’Neill 8JTDPOTJOo.BEJTPO Duanqing Pei Carol C. Shoulders Space is limited, and registration is Robert D. Wells t+FSPNF $ /XBDIVLXV 4BDLMFS accepted when registering for Experi- *OTUJUVUF PG (SBEVBUF #JPNFEJDBM ASBMB Today mental Biology (EB) 2008. The cost is 4UVEJFT /FX :PSL 6OJWFSTJUZ Nicole Kresge Editor $20 for ASBMB members and $25 for [email protected] 4DIPPM PG .FEJDJOF BOE all other EB registrants. Nancy J. Rodnan Director of Publications t.JUJ4IBI "SJ[POB 4UBUF [email protected] Please note that if you are a 6OJWFSTJUZ Barbara Gordon Executive Director Graduate Minority or Graduate/Post- [email protected] “We wanted to reach out to doctoral Travel Award recipient, reg- Magazine design & production: Amy Phifer younger members,” says Dodge- istration for the program is included For information on advertising contact Kafka,“ to provide them some advice as part of your travel award. FASEB AdNet at 800-433-2732 ext. 7157 or 301-634-7157, or E-mail [email protected]. on training and career options and We hope all postdocs and gradu- to make them feel more included in ate students will plan to attend. And Society affairs.” please, all you “seasoned” investiga- The day-long event kicks off on tors, make sure to encourage your www.asbmb.org Saturday, April 5, 2008, with a panel students to attend.
November 2007 washington update FA S E B FASEB Comments on Biosecurity Oversight Proposal BY CARRIE D. WOLINETZ
arlier this year, the National Science Advisory Board IBCs, and Institutional Review Boards (IRBs), the difficulty Eon Biosecurity (NSABB), the federal advisory group in identifying what is to be overseen is unique. One is tasked with developing guidelines for dual use biologi- either using animals, recombinant DNA, or human sub- cal research (i.e. research that can be used for positive jects and is therefore subject to review, or one is not. This benefit or misused to cause harm), released a draft report is in contrast to dual use research, in which the need for on a proposed oversight framework for dual use research. review is subject to a great deal of interpretation. NSABB The document details guidance for the identification, itself found that there were “significant differences in review, and communication of what NSABB terms dual assessments made by individual NSABB members” and use research of concern, or DURC. The major points of that there were “difficulties inherent in explicitly defining the proposal include: the point at which the magnitude and/or immediacy of the s 2ECOMMENDATIONS FOR MANDATORY TRAINING FOR ALL SCIENTISTS threat of misuse makes dual use research ‘of concern.’” TRAINEES AND STAFF ABOUT DUAL USE RESEARCH Because of the difficulties in identifying research to be s !LL PRINCIPAL INVESTIGATORS WOULD REVIEW THEIR RESEARCH reviewed, FASEB also expressed concerns related to the PROGRAM TO SEE IF IT MATCHES THE CRITERIA FOR $52# BASED ON A QUESTIONNAIRE DEVELOPED BY .3!"" IF NOT THEY WOULD feasibility and potential burden of the system. In particular, CHECK A BOX ON GRANT APPLICATIONS TO THAT EFFECT AND AGREE the vagueness of the criteria could lead to vast under- TO YEARLY REVIEW reporting by investigators or overreporting by institutions s 2ESEARCH IDENTIlED AS $52# WOULD TRIGGER AN INSTITUTIONAL concerned about liability. Either scenario diminishes the RISK ASSESSMENT BASED REVIEW PERHAPS THROUGH THE EXISTING goal of increasing security. Also of security concern are )NSTITUTIONAL "IOSAFETY #OMMITTEES )"#S AND DEVELOPMENT OF SUBSEQUENT RISK MANAGEMENT AND COMMUNICATIONS PLANS the products that could potentially be produced during the .3!"" ALSO PROVIDES TOOLS AND GUIDANCE FOR DEVELOPMENT review process. The scientific and security communities OF SUCH PLANS have struggled, in a number of venues, with the concept s 2ECOMMENDATION FOR MANDATORY COMPLIANCE WITH DUAL USE of “sensitive but unclassified” information. The proceed- OVERSIGHT GUIDANCE AND PENALTIES FOR NON COMPLIANCE ings of dual use review meetings, the documents provided s 2ECOMMENDATIONS THAT SCIENTIlC SOCIETIES DEVELOP CODES by NSABB as tools for review, or the documenting of deci- OF CONDUCT FOR DUAL USE RESEARCH AND PROVIDE GUIDANCE AND sions that identify research that may merit discontinuation SAMPLE LANGUAGE FOR CODES or restrictions on publication: whose responsibility is it to s ! LATITUDE FOR INTERPRETATION DELIBERATELY SO THAT FEDERAL AGENCIES CAN MAKE THEIR OWN DETAILED REGULATIONS ensure their security? Many questions are raised by a pro- Although NSABB does not have the authority to issue cess that highlights research of security concern and then official regulations, the reality is such that government attempts to retroactively control information related to it. guidelines are often given the force of regulation in their The entire FASEB letter and analysis may be read implementation by the federal agencies. In addition, the at: opa.faseb.org/pdf/NSABB.Final.8.8.07.pdf, and agencies that serve as ex-officio members of NSABB the NSABB proposal may be found on their Web site: could initiate a regulatory rulemaking process based on www.biosecurityboard.gov. It remains to be seen what NSABB’s proposal. the next steps for NSABB or the federal government FASEB submitted a lengthy analysis and comment let- are in regard to modifying or moving forward with this ter to NSABB in response to the board’s request for input proposal, but in the meantime NSABB has been focusing from the scientific community. Chief among our concerns on working with the international community in an effort is the ambiguity and subjectivity inherent in identifying to inform and coordinate with other nations on dual use dual use research of concern. Although the NSABB pro- biosecurity issues. posal is modeled after other regulatory schema, such as Institutional Animal Care and Use Committees (IACICs), Carrie D. Wolinetz is with the FASEB Office of Public Affairs.
November 2007 ASBMB Today 3 news from the hill .)( .3& &UNDING "ILLS "EGIN TO -OVE BY PETER FARNHAM
n October 3, Senator Tom Harkin’s (D-IA) staff con- to urge all senators to support the measure and then, Ovened a meeting of representatives of various health, assuming it passes and is conferenced with the House, education, and labor groups (including ASBMB and FASEB to pressure the White House not to veto the bill. staff) to discuss the status of the 2008 Labor/Health & The bill is expected to undergo a quick conference due Human Services (HHS) Appropriations bill. He asked for to the similarity between the House and Senate versions, grassroots support of all and it is hoped that the bill interested parties, includ- will pass the Senate the ing advocacy groups for week of October 16, follow- biomedical research. Since ing the Senate’s Columbus the National Institutes of Day recess, and then go Health (NIH) is funded under to the President in early this bill, the bill is obviously November. Staff has begun of considerable concern to pre-conferencing, and ASBMB. Harkin has been in touch The Senate version of the with House Appropriations bill allocates $29.9 billion to Chair David Obey (D-WI). NIH for fiscal year (FY) 2008, Harkin urged the community $800 million (2.8%) over FY to refrain from supporting 2007. ASBMB has up to amendments that would now supported a $1.9 billion rearrange funding, includ- increase (6.7%) for three ing amendments to offset years, intended to recover spending increases for cerr- the agency’s purchasing tain programs with across power lost since the dou- the board cuts of the bill. bling of the agency’s budget He also solicited ideas was completed in FY 2003. for increasing publicity on The Senate’s proposed the bill, particularly as the increase is less than half expected Presidential veto what ASBMB has sup- will come on the heels of the ported and does not keep October 3 veto of the State pace with biomedical infla- Children’s Health Initiative tion. Nevertheless, it is $1.2 Program (SCHIP). It is hoped billion over the President’s that increased visibility and request for FY 2008, and pressure may dissuade the the overall bill exceeds White House from a veto his budget request by “showdown.” It is not yet $12 billion. These facts clear whether the measure have already prompted a will garner enough support veto threat from the White to override a veto. The curr- House. Harkin and Senator rent read on this is that the Arlen Specter (R-PA) are votes are there for an overr- requesting the mobiliza- ride in the Senate but not in tion of grassroots groups the House.
4 ASBMB Today November 2007 President Bush has threatened to veto 9 of the 12 regular dent proposed a $500 million appropriations bills in their current form because together increase at NSF for FY 2008 they exceed by $22 billion his avowed spending limit of to $6.4 billion. The House bill $933 billion in discretionary spending for 2008. proposes to increase NSF The battle over the additional spending Congress wants spending by $600 million, comes against the backdrop of an administration request and the Senate bill proposes for an additional $42 billion in supplemental spending for a $700 million increase. the war in Iraq and Afghanistan. FASEB Legislative Affairs Unfortunately, the President Director Jon Retzlaff notes that the current spending battle has threatened to veto this between Congress and the White House makes the govern- appropriations bill as well ment as divided as it’s been since the federal shutdown of because of proposed Con- 1995. “The President has drawn a line in the sand at limiting gressional spending above the total spending to $933 billion in FY 2008,” Retzlaff noted, President’s request and also “and is receiving support from House Republicans, who because of report language have been arguing all year that they lost Congress by not regarding NSF found in the staying true to their principles, particularly on controlling House version. spending. Democrats are adamant that many programs Most of the proposed besides those related to defense, homeland security, veterr- increase at NSF under the House and White House pro- ans, and foreign operations deserve to be supported. There- posals would be concentrated in support of several dis- fore, it’s extremely likely that we will be discussing the FY ciplines—math, physics, chemistry, computer sciences, 2008 appropriations process well into December.” FY 2008 and engineering. ASBMB supports these increases but of course began on October 1. has also called for comparable increases in the biological sciences directorate, which would receive less than half Continuing Resolution of the increases proposed for the other disciplines listed All programs funded under appropriations bills are curr- above. ASBMB is thus supporting a letter to the Senate rently operating under a continuing resolution (CR) through calling for a redress of the disparity between the spending November 16. Chairman Harkin predicted there would be levels in the various directorates. a second CR, perhaps lasting until December 21, with daily The letter takes note of report language in the House funding extensions possible if needed. bill that makes this point: The House has passed all 12 appropriations bills, but h4HE #OMMITTEE STRONGLY SUPPORTS INCREASES FOR the Senate has approved only 4. Under the CR, federal THE MATH AND PHYSICAL SCIENCES COMPUTER SCI- government agencies and pro- ENCES AND ENGINEERING DIRECTORATES IN lSCAL YEAR grams, including NIH, the National FOR RESEARCH AND RELATED ACTIVITIES 22! Science Foundation (NSF), the (OWEVER THE #OMMITTEE ALSO BELIEVES THE &OUNDA- Department of Energy’s (DOE’s) TION SHOULD MAINTAIN COMPARABLE GROWTH IN lSCAL Office of Science, the Department YEAR FOR THE BIOLOGICAL SCIENCES GEOSCIENCES of Agriculture’s National Research AND SOCIAL BEHAVIORAL AND ECONOMIC SCIENCES Initiative, and the National Aero- DIRECTORATES !S THE )NNOVATION !GENDA MOVES FOR- nautics and Space Administration WARD IT IS IMPORTANT TO NOTE THATMAINTAINING 53 (NASA), will be funded at the same COMPETITIVENESS WILL DEPEND ON ADVANCES IN AND level as in 2007. THE INTERACTIONS AMONG ALL lELDS OF SCIENCE 4HE Committee expects NSF to ensure that the bio- NSF Gets Good Increase, LOGICAL SCIENCES GEOSCIENCES AND SOCIAL BEHAV- but Veto Looms Here, Too IORAL AND ECONOMIC SCIENCES DIRECTORATES RECEIVE Congress and the President are INCREASES IN lSCAL YEAR THAT ARE COMPARABLE in agreement that the National to the other directorates.” Science Foundation’s budget The letter urges Senators to support inclusion of this should be increased. The Presi- language in the conference report.
November 2007 ASBMB Today 5 asbmbfirstsecond member spotlightwords
Malamud Awarded Gilbert to Become Head $6.25 Million NIH Grant of Biology at Rensselaer Daniel Malamud, a professor of basic Polytechnic Institute science and craniofacial biology at the New Susan P. Gilbert, an expert in cell biology, York University College of Dentistry biophysics, and nanoscience, joined (NYUCD), has been awarded a five year, Rensselaer Polytechnic Institute as the head $6,258,768 grant from the National Institute of the Biology Department this past of Dental and Craniofacial Research (NIDCR) September. Gilbert joins the Rensselaer of the National Institutes of Health (NIH) to faculty after 12 years at the University of head up a research collective consisting of Pittsburgh. four interrelated research projects along with Gilbert plans to build on the key administrative/biostatistical and clinical core components. strengths of the Biology Department. “With The collective’s overall goal is to define the interactions the hiring of top-level constellation chairs and faculty, the Biology between host defense molecules and bacteria in HIV infection and Department has an extremely strong foundation,” she said. “I hope subsequent antiretroviral therapy. The collective consists of teams to build on this foundation by utilizing Rensselaer’s strong interdis- from NYUCD, New York University School of Medicine, and the ciplinary approach to research and learning. In this environment, Aaron Diamond AIDS Research Center. we can rapidly incorporate new approaches for undergraduate and “The study is an intriguing one,” notes Malamud. “We are going graduate education.” to recruit a population of people that are HIV-infected but are drug Gilbert has spent more than 20 years in higher education. naïve, so they haven’t even been put on treatment yet. New York At the University of Pittsburgh she served on the faculty of the City is probably one of the few places in the country where the Department of Biological Sciences. During her time there she study could be done.” was a member of the Molecular Biophysics and Structural Biol- The entire proposal utilizes the same case-controlled study ogy Graduate Program and the University of Pittsburgh Cancer population consisting of 85 HIV positive, therapy-naïve subjects Institute. whose illness is highly aggressive who will subsequently begin anti- Gilbert is known for her research on cell motility. She studies retroviral therapy. There will also be a similar cohort of HIV-negative the interaction of kinesins with microtubules, working to under- subjects. stand the kinesins that function in cell division.
Fields Earns Vollum Award Benos Named Distinguished Stanley Fields, a Howard Hughes Medical Faculty Lecturer Institute (HHMI) Investigator at the University Dale J. Benos, chair of the Department of of Washington School of Medicine, has Physiology and Biophysics at the University received the 2007 Vollum Award for of Alabama at Birmingham (UAB), is the Distinguished Accomplishment in Science recipient of the university’s 2007 Distin- and Technology from Reed College. guished Faculty Lecturer Award—the UAB The award was created and first Academic Health Center’s most prestigious presented by Reed College in 1975. It faculty award. Benos received the award recognizes and celebrates the exceptional and presented a lecture at a banquet held in achievement of one or more members of the scientific and techni- his honor in October. cal community of the Northwest. The name of the award is a trib- The award acknowledged Benos’ many achievements and the ute to the late Howard Vollum, one of the nation’s great innovators high regard in which he is held by his peers. It was also a reflection and technologists and a Reed physics alumnus. of his contributions to the university and the community. “Like the traits prized for the Vollum Award, creativity, risk Benos’ research centers on ion channels and membrane- taking, exploration of unproven avenues, and an embrace of transport processes. He focuses on a number of disease states the unknown mark HHMI appointees, Fields’ research career is and the involvement of proteins in diseases such as hypertension emblematic of these traits and of his unquenchable curiosity,” said and cystic fibrosis. His laboratory also is investigating the role of Janis Shampay, a professor of biology at Reed. ion channels and transporters in human brain tumors. Fields developed the yeast two-hybrid system, which detects Benos has chaired the Department of Physiology and Biophys- interactions between two different proteins in living cells. He and ics since 1996 and holds secondary appointments in the Depart- his colleagues also published the first analysis of all possible yeast ments of Cell Biology, Neurobiology, and Physiological Optics. In protein interactions, which involves 6,000 proteins. addition, he is a senior scientist in eight research centers. He is FIELDS PHOTO: PAUL FETTERS also an associate editor for the Journal of Biological Chemistry.
6 ASBMB Today November 2007 Please submit news about yourself to [email protected]
Spector Receives Leaf Boutaud Receives Gilbert Distinguished Scientist Award Foundation/AFAR New Arthur Spector, the University of Iowa Investigator Award Foundation Distinguished Professor of Olivier Boutaud, assistant professor at Biochemistry and Internal Medicine in the Vanderbilt University Medical Center, was Roy J. and Lucille A. Carver College of one of six early-career scientists who were Medicine, has been named the recipient of awarded the first Rosalinde and Arthur the Alexander Leaf Distinguished Scientist Gilbert Foundation/American Federation for Award from the International Society for the Aging Research (AFAR) New Investigator Study of Fatty Acids and Lipids (ISSFAL). Award in Alzheimer disease. The award was established by the soci- The $60,000 award provides funding for ety in 2002 to honor the work of Alexander Leaf and his support a broad array of research that investigates for ISSFAL and to recognize and reward excellence in areas of the causes and progression of Alzheimer disease, including the research relevant to ISSFAL core interests. basic mechanisms of aging, genetics, biomarkers, inflammation, Spector will deliver the featured lecture during the opening cer- and the impact of exercise and the environment. emonies of the ISSFAL’s eighth international meeting in May 2008. Boutaud’s proposal was titled “Quantification of the relative Spector’s research focuses on fatty acids in biological systems. abundance of secreted Amyloid precursor protein (APP) alpha and In particular, he is interested in the role of polyunsaturated fatty beta as a biomarker of Alzheimer’s disease.” He will determine acids in vascular disease and how they affect the function of brain whether levels of secreted APP A and B could serve as an effective cells. biomarker for Alzheimer disease. This biomarker could poten- Spector served as the president of ISSFAL from 2000 to 2003. tially be used as a prognostic tool to track the progression of the He is a member of the advisory board for the journal Progress in disease as well as monitor the biological effects of new therapeutic Lipid Research and Prostaglandins and Other Lipid Mediators. He agents. is on the editorial board of the Journal of Lipid Research and chairs “The Rosalinde and Arthur Gilbert Foundation has invested in the scientific advisory board for Wake Forest and Brigham and an outstanding group of researchers who have the potential to Women’s Botanical Lipids Center. make important and lasting contributions to Alzheimer disease and aging science,” said Martin H. Blank, Jr., co-director of the Maccarrone Honored Rosalinde and Arthur Gilbert Foundation. with IACM Award IN MEMORIAM Mauro Maccarrone, professor of biochemis- try and chairman of biotechnology at the Rosalind Kornfeld 1935–2007 Rosalind Hauk Kornfeld passed away on University of Teramo (Italy) and chief of the August 10, 2007. She was born in 1935 in Laboratory of Lipid Neurochemistry of the Dallas, Texas, and graduated from George European Center for Brain Research-S. Washington University in 1957 with a B.S. in Lucia Foundation (Rome, Italy), has received chemistry. Kornfeld then earned a doctorate the 2007 Award for Basic Research from the in biochemistry from Washington University International Association for Cannabis as in St. Louis in 1961. She subsequently Medicine (IACM). stayed on as a postdoctoral fellow until 1963 The IACM award consists of a cash prize and a plaque, and the when she joined the National Institutes of award is presented every second year to recognize “the special Health as a fellow. In 1965, Kornfeld joined the faculty of Washing- achievements of a candidate who has made a major contribution ton University School of Medicine where she spent the rest of her to the re-introduction of cannabis and cannabinoids as medicine academic career. In 1969, she was promoted to research assistant through basic research.” Maccarrone was honored in October at professor; in 1971, research associate professor; in 1978, the 4th IACM biennial conference during a gala dinner in Cologne, associate professor; and in 1981, full professor of medicine and Germany. professor of biochemistry and molecular biophysics. Maccarrone’s studies have revealed molecular details of the For almost 40 years, Kornfeld’s research focused on the dysregulation of the endocannabinoid system that underlie human structure and biosynthesis of oligosaccharide chains on glycopro- pathologies like spontaneous miscarriage, headache, Parkinson teins. She was among the first to discover the structure of many disease, Huntington disease, and multiple sclerosis. His work has oligosaccharides and to characterize how they were formed. contributed to the identification of novel regulatory pathways that have led to new diagnostic tools and therapeutic strategies for the treatment of those diseases, based on endocannabinoid-oriented drugs.
November 2007 ASBMB Today 7 asbmb news -ARIO 2 #APECCHI 2ECEIVES .OBEL 0RIZE IN 0HYSIOLOGY OR -EDICINE
SBMB member Mario R. Capecchi, a distinguished years he lived on the streets, fending for himself by begging Aprofessor of human genetics and biology at the and stealing. He reunited with his mother when he was nine, University of Utah’s Eccles Institute of Human Genetics and they soon came to the United States where Capecchi and a Howard Hughes Medical Institute investigator, was began elementary school. As a result, he didn’t learn to read awarded one-third of this year’s Nobel Prize in Physiology or write until he was nine years old. or Medicine. He shared the prize with Sir Martin J. Evans “I think [this experience] provided resourcefulness, and I of Cardiff University in the United Kingdom and Oliver think just the drive to keep yourself, maintain yourself, and Smithies of the University of North Carolina at Chapel Hill survive,” said Capecchi. “I think it led me to be able to use “for their discoveries of principles for introducing specific my own resources, to be able to get through life. And I think gene modifications in mice by the use of embryonic stem now I’m also very grateful; in a sense it’s fantastic. I mean cells.” The prize recognizes Capecchi’s pioneering work most children didn’t make it; I think I was extremely lucky.” in gene targeting in mice, a technique that has revolution- Capecchi received his B.S. in chemistry and physics ized mammalian biology and “…for discoveries of principles for introducing specific g allowed the cre- ation of animal models for hundreds of human diseases. from Antioch College in 1961 and his Ph.D. in biophysics In the 1980s, both Capecchi and Smithies were seeking from Harvard University in 1967. He completed his the- ways to specifically alter the mammalian genome. Capec- sis work under the guidance of Nobel laureate James D. chi wanted to insert new genes into cells, and Smithies Watson, whom he credits for inspiring his development as a was hoping to correct genetic defects that lead to disease. scientist. Capecchi was able to demonstrate that homologous recom- “He taught me not so much about how to do science bination could take place between introduced DNA and the but rather provided me with the confidence to tackle any chromosomes in mammalian cells and was thus able to scientific question that fascinated me, regardless of its repair defective genes. Smithies showed that that endog- complexity,” said Capecchi. “He also taught me the impor- enous genes could be targeted irrespective of their activity, tance of communicating your science clearly and to pursue suggesting that all genes were accessible to modification important scientific questions.” by homologous recombination. Thus, the two scientists After receiving his Ph.D., Capecchi joined the faculty of independently discovered that they could use homologous the Department of Biochemistry at Harvard Medical School. recombination to introduce short sequences of manipulated He stayed there for four years, and then, in 1973, he left to DNA into the chromosomes of mammalian cells. join the University of Utah faculty. However, the cell lines initially studied by Capecchi His entry into what was going to become the field of and Smithies could not be used to create gene-targeted gene targeting started in 1977 when he was experiment- animals. Fortunately, Evans had developed embryonic stem ing with the use of extremely small glass needles to inject cell cultures that were able to take the genetic manipula- DNA directly into the nuclei of living cells. He attempted to tions from the Petri dish into the whole animal. Combining introduce a functional gene into cells by injecting the DNA the techniques by modifying genes in embryonic stem cells directly into their nuclei, and he succeeded. Because the and then injecting those cells into fertilized mouse eggs, the procedure turned out to be extremely efficient—one in scientists were able to produce mice with specific genetic three cells received the DNA in functional form and went modifications that could be inherited between generations. on to divide and pass the gene on to its daughter cells—it Capecchi was born in Verona, Italy, in 1937. At the became practical to use this technology to generate trans- age of four, he was separated from his mother, who was genic mice by the injection of DNA into one-cell zygotes. imprisoned during World War II. For the next four and a half Capecchi recalls, “I realized immediately that, if I could
8 ASBMB Today November 2007 c gene modifications in mice by the use of embryonic stem cells.”
harness this machinery to carry out homologous recombi- disrupt the hprt gene, and he showed that embryonic stem nation between a newly introduced DNA molecule of our cells were indeed able to mediate homologous recombina- choice and the same DNA sequence in the cell’s chromo- tion. The first reports in which homologous recombination in some, I would have the ability to mutate at will any specific embryonic stem cells was used to generate gene-targeted gene in the living cell.” mice were published in 1989. Since then, the number of However, in 1980, when he submitted a grant application reported knock-out mouse strains has risen exponentially. to the National Institutes of Health in which he outlined the Gene targeting has since developed into a highly versatile experiments he intended to do to test the feasibility of gene technology. It is now possible to introduce mutations that targeting in mammalian cells, the grant was rejected. can be activated at specific time points or in specific cells or “Our first grant was actually refused with respect to that organs, both during development and in the adult animal. project, mainly because they didn’t think it was possible,” Over the years, Capecchi has used gene targeting to said Capecchi. “The probability that an exogenous piece systematically knock out genes in the Hox family. These are of DNA would be able to find the cognate sequence in 33 thought to be the master switches that control the formation base pairs was thought to be not a significant possibility.” of the body plan during development. The knock-out mice Despite this rejection, he forged ahead with his experi- have dramatic developmental defects. For example, when ments and succeeded. The next step was to extend gene Capecchi completely disrupted the Hox10 and Hox11 gene targeting to a whole animal. “Because of the low frequency families, he found that the genes played important roles in of targeting events in mammalian cells, it was clear that orchestrating the construction of the ribs, spine, and limb doing the experiments directly in mouse zygotes would not bones. Mice without a functional Hoxb8 gene on the other be practical,” recalls Capecchi. “Rather, targeting events hand, groomed themselves excessively, creating bald spots had to be identified first in cultured cells to allow purification and skin wounds. of a clonal cell line containing the desired gene disruption; Capecchi and his colleagues have also developed the these cells in turn could be used to generate mice capable first accurate mouse model of alveolar rhabdomyosarcoma, of transmitting the mutation in their germline.” an aggressive childhood muscle cancer. This new model Capecchi heard about Evans’ embryonic stem cells at has improved researchers’ understanding of the cause a Gordon Conference in 1984, and a collaboration was of the disease and may lead to new therapies to treat the initiated. For the initial experiments Capecchi decided to disorder.
November 2007 ASBMB Today 9 specialinterest
The following graphs are part two of a series of data compiled by Howard Garrison and Kimberly McGuire of FASEB’s Office of Public Affairs.Th e graphs represent trends in postdoctoral training. The final installment of graphs will appear in Today
NIH F32 Fellowship Applications Reviewed and Awarded
3,000 50% 45% 2,500 40% 35% 2,000 30% 1,500 25%
NUMBER 20% 1,000 15% 10% 500 5% 0 0% 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 S YEAR ). Applications Awards Success Rate
NIH Spending on Training Grants and Fellowships Since 1983, to 900,000 5.00 spending o grants a 800,000 4.50 for po 700,000 4.00 has 3.50 600,000 the 3.00 pe 500,000 2.50
N DOLLARS 400,000 fr 2.00 300,000 SO 1.50 SU 200,000 BUD 1.00 HISTO 100,000 0.50
0 0.00 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 2005 2007
YEAR
Dollars Percent of total NIH Budget
10 ASBMB Today Doctorate Degrees Awarded in the Biological and Medical Sciences by Citizenship/Visa Status
8,000
7,000
6,000
5,000
4,000
NUMBER 3,000
2,000
1,000
0
1966 1969 1972 1975 1978 1981 1984 1987 1990 1993 1996 1999 2002 2005 YEAR
Temporary Residents U.S. Citizens and Permanent Residents Unknown Citizenship
to SOUR
Doctorate Degress Awarded in the Biological and Medical Sciences by Gender
8,000
7,000
6,000
5,000
4,000
NUMBER 3,000
2,000
1,000
0
1966 1969 1972 1975 1978 1981 1984 1987 1990 1993 1996 1999 2002 2005 YEAR
Unknown Gender Female Male
November 2007 ASBMB Today 11 trends continuedcontinued
Biological and Medical Sciences Postdocs by Citizenship/Visa Status
35,000
30,000
25,000
20,000
15,000 NUMBER
10,000
5,000
0
1979 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 YEAR
Temporary Residents US Citizens and Permanent Residents
Biological and Medical Sciences Postdocs by Source of Support
35,000
30,000
25,000
20,000
15,000 NUMBER
10,000
5,000
0
1979 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 YEAR
Non-Federal Sources Research Grants Traineeships Fellowships
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--;+ "; C@ ? C B> ? < @ 2008 annual meeting The 2008 Herbert Tabor/ Journal of Biological Chemistry Lectureship: I. Robert Lehman
Lehman he 2008 Herbert Tabor/Journal of Biological Chemis- ies greatly contributed to the under- Ttry Lecture will be given by I. Robert Lehman at next standing of the mechanics of DNA replication in the cell.1 year’s annual meeting. Lehman received the award for In the late 1970s, Lehman’s inquisitive spirit led him to his outstanding scholarly contributions to the field of DNA new directions of DNA research. He extended his DNA metabolism, his admirable track record as a mentor, and his replication studies to eukaryotic and viral organisms, and unparalleled service to the Journal of Biological Chemistry. he initiated homologous recombination studies in E. coli. He will present his lecture in San Diego on Saturday, April 5, His biochemical studies of DNA recombination catalyzed at 6:00 pm. by the E. coli recA protein were among the first in the field Lehman’s career in DNA metabolism research started and have become a template for subsequent analyses of in 1955 when he joined Arthur Kornberg’s laboratory at recombination in eukaryotic cells. Washington University in St. Louis as a postdoctoral fellow. Lehman was named William Hume Professor at Stanford During the next three years he and other members of the University in 1980 and continues in this position today. He Kornberg laboratory discovered the first DNA polymerase, served as chairman of the Department of Biochemistry from DNA polymerase I from Escherichia coli, and showed that 1974 to 1979 and from 1984 to 1986. it was a template-directed enzyme. This work eventually Lehman was president of ASBMB from 1997 to 1998, earned Kornberg one-half of the 1959 Nobel Prize in Physi- was on the editorial board of the Journal of Biological ology or Medicine. Chemistry from 1963 to 1968, and has served as an asso- In 1958, Lehman began independent research as an ciate editor for the journal since 1981. “All of us working instructor in the Department of Microbiology at Washington in the nucleic acid field are aware of Bob’s devotion to the University. There, he discovered many of the E. coli deoxy- Journal of Biological Chemistry,” says Charles C. Richard- ribonucleases and demonstrated their usefulness for study- son, Edward S. Wood Professor of Biological Chemistry at ing nucleic acid structure. He left Washington University in Harvard Medical School. “It is always a pleasure to receive 1959 to join the faculty of the Biochemistry Department at an e-mail notification that the associate editor for your the Stanford University School of Medicine. Lehman con- manuscript is I. R. Lehman. Not only is the review prompt tinued his search for DNases in E. coli and other organisms but also the reviewers always seem perfectly matched with and purified several of these enzymes. the manuscript.” In the late 1960s, Lehman started searching for a new Lehman’s stellar scientific output is matched by the area of research and decided to look for the enzymes that large number of scientists who trained in his lab. “Bob has catalyzed the joining of DNA molecules. As he was purify- passed his excellence and insistence for quality and integrity ing the polynucleotide joining enzyme, he became aware in research to a number of students and postdocs who that several other laboratories were working on the same have had the privilege of working in his laboratory. Indeed, problem in a variety of organisms. Each group had its own not only have these individuals been successful, they have name for the enzyme, but they all settled on “DNA ligase,” also served the Society and the JBC in many major capaci- and friendly competition between the labs ensued. Leh- ties,” says Stuart Linn, Professor of the Graduate School man was able to work out the complex mechanism of this Division of Biochemistry and Molecular Biology at the Uni- enzyme involving multiple nucleotide transfer steps. His versity of California Berkeley.
insights into the origins and closure of DNA nicks resulted FOOTNOTE in a critical study that determined the causes of the gen- 1. More information on Lehman’s research on DNA ligase can be found in his online Journal of Biological Chemistry Classic 1. eration of small DNA fragments in the cell that had been REFERENCE erroneously designated as Okazaki fragments. These stud- J. Biol. Chem. 282, 1, January 12, 2007.
14 ASBMB Today November 2007 The 2008 ASBMB Merck Award: C. David Allis
he 2008 ASBMB Merck Award will be given to C. The discovery that two enzymes TDavid Allis, the Joy and Jack Fishman Professor at that were involved in adding and Allis Rockefeller University, at the ASBMB Annual Meeting this subtracting acetyl groups to and from April. He receives the award for his seminal contributions histones also enhanced or repressed transcription sug- to the field of chromatin biology. Allis’ research has helped gested a molecular mechanism for transcriptional regula- to define cause and effect relationships between specific tion. “It wasn’t rocket science to figure out this enzymatic histone modifications and specific gene expression events. pair of reactions might function as an on or off switch,’’ He has also aided in defining the enzymes and mecha- said Allis. “Most people thought chromatin was just a pas- nisms involved in epigenetic regulation. Allis will present his sive platform that wraps the DNA. But those two papers award lecture on Monday, April 7, from 2:15 to 3:15 pm. made people think about a more active process in which Allis, who received his Ph.D. in 1978 from Indiana Univerr- chromatin truly participates’’ 1. sity, first became interested in chromatin during his post- Moving on to yeast, Allis went on to provide the first doctoral fellowship with Martin Gorovsky at the University of definitive evidence that histones are physiological targets Rochester. He used the ciliated protozoan Tetrahymena as of GCN5 and are acetylated by GCN5 a specific residues, his model organism. He recalls, “This was a relatively new that the GCN5 HAT activity is required for transcriptional topic back then. It wasn’t by any means the raging topic activation and targets promoter-proximal histones, and that it is today, and to think about doing chromatin biology that histone acetylation is independent of, and thus caus- in a super low, offbeat critter was not fashionable” 1. ative for, transcription. After his postdoctoral fellowship was over, Allis became Beyond these critical histone acetylation studies, Allis an assistant professor in the Department of Biochemistry has shown that histone H3 phosphorylation on an invariant at the Baylor College of Medicine in 1981. Over the next serine is functionally linked to both mitosis and to mitogen decade, he moved up the ranks and eventually became stimulation of gene activity, that specific kinases are involved full professor in the Departments of Biochemistry and Cell in this phosphorylation process, and that specific phospho- Biology at Baylor. He then spent five years as a professor rylation events can enhance specific acetylation events. in the Department of Biology at Syracuse University before Allis has also made seminal observations on the role of joining the faculty of the Department of Biology at the Uni- histone methylation events in gene control. He has shown versity of Rochester in 1995. Allis joined the faculty of the that the addition of methyl to certain lysine residues on his- University of Virginia in 1998. tone H3 corresponds with the activation of transcription. In 1996, Allis isolated a protein from Tetrahymena He and his collaborators have also been instrumental in that was able to add an acetyl group to exposed lysine the identification of specific histone methyltransferases and residues in histones. This was the first histone acetyl- the characterization of their corresponding complexes. transferase (HAT) to be identified. He then showed that Based on observations of multiple histone modifications HAT from Tetrahymena was the homolog of a genetically of the same histone tail, Allis formulated the “histone code” defined transcriptional coactivator (GCN5) from yeast and hypothesis, which posits that different modifications or that the yeast GCN5 coactivator had intrinsic HAT activity. combinations of modifications may act to form an epi- This single observation immediately crystallized mecha- genetic code that can be translated into different nuclear nistic concepts about direct linkages between histone responses. More recently, Allis has extended this hypoth- acetylation and transcriptional activation. esis and proposed new principles that include histone A month after finding HAT, Allis characterized an “modification cassettes” and “switches.” enzyme that removed acetyl groups from histones. This histone deacetylase was related to a transcriptional core- REFERENCE 1 Downey, P. (2006) Profile of C. David Allis. Proc. Natl. Acad. Sci. (U. S. A.) 103, pressor in yeast. 6425-6427.
November 2007 ASBMB Today 15 minorityaffairs Minority Student Conferences: ASBMB’s Involvement BY PHILLIP A. ORTIZ
ach fall, members of ASBMB’s Minority EAffairs Committee (MAC) participate in two scientific meetings—one organized by the Soci- ety for the Advancement of Chicanos and Native Students gather at the 2006 ABRCMS Conference. Americans in Science (SACNAS) and the Annual Biomedical Research Conference for Minority number of years Landefeld and Ortiz have also been lead- Students—that are of particular interest to minority stu- ing a well attended session titled, “Career Development in dents. Since aligning with these meetings, the committee has the Biochemical Sciences: What Can Professional Societies become more actively engaged with each succeeding year Do for You?” In this session students are informed of the and has increased ASBMB’s visibility. At these meetings two benefits they can expect from—as well as their responsibili- members of the MAC with ASBMB meetings coordinator, ties to—professional scientific societies. In addition to an Gail Pinder, “work the ASBMB booth” and participate as engaging presentation, students are provided with a set of leaders in other aspects of the meeting. career materials and student centered literature from the The ultimate goal of both meetings is to enhance the ASBMB. The session is especially important because a large educational experience and quality for all attendees by pro- number of undergraduate students do not have extensive viding the students with many educational and professional knowledge about professional scientific societies, and many development opportunities. At the ASBMB booth, volunteers other societies are present at the meeting, competing for the and staff talk with dozens, if not hundreds, of undergraduate, students’ attention and possible membership. graduate, and post-doctoral students and their faculty men- The SACNAS meeting is very much like being with several tors who want to learn more about our organization. Other thousand of your closest family members and friends. The opportunities come in the form of student poster and oral environment is particularly warm and inviting as everyone presentations and by attending of many outstanding presen- freely shares their insights and expertise. No opportunity for tations and interactive sessions offered. A large number of mentoring, coaching, or providing support and encourage- these students are either directly involved in research, or at ment is overlooked. Activities at this meeting include not least are aware of its benefits, and are very often sponsored just oral scientific and career sessions led by faculty but also by federally funded minority programs, mostly from the student led poster and oral presentations and a highly engag- National Institute of General Medical Sciences at the National ing Pow Wow. Institutes of Health. The second of the two meetings is the Annual Bio- The SACNAS meeting (www.SACNAS.org) draws stu- medical Research Conference for Minority Students dents from across many scientific disciplines and math- (www.ABRCMS.org). This meeting, unlike SACNAS, ematics. SACNAS is a unique organization in that it highly focuses primarily on undergraduate students engaged in the values mentoring and development of young scientists. In biomedical sciences who wish to pursue scientific careers in fact, in recent years, two members of the ASBMB MAC this area. As such, our booth is overrun by many students have been honored with the “Award for Outstanding Men- who ask focused questions, gather literature, collect guid- tor at an Undergraduate Institution.” Tom Landefeld won ance and suggestions, and share their own stories of frustra- the award in 2002, and Phillip A. Ortiz won in 2005. For a tion and success.
16 ASBMB Today November 2007 In past years members of ASBMB MAC have played key recruiting a loyal member and future leader in our organi- roles in the ABRCMS meeting. For example, Landefeld and zation. Ortiz have each served full terms on the meeting’s steering The student work presented at both of these meetings committee and helped to formulate the priorities and agenda is stringently pre-screened for scientific quality. Always over the past six years. In addition, for a number of years, astounding is the quality of the students’ research, their abil- Ortiz has served as leader of the biochemistry and molecu- ity to present and discuss it, and their depth of knowledge. As lar biology sessions. In that role he has reviewed hundreds students present their posters, they are amid crowds of faculty of abstracts for quality, reviewed travel award applications, mentors and research advisors as well as other engaged stu- moderated oral presentation sessions, and served as a judge dents. In fact, one of the students who presented a poster at for both the poster and oral presentations. ABRCMS later presented an improved version at the ASBMB Undergraduate Poster Competition—and he was awarded first prize! These meetings each end in a festive award banquet. At these dinners, awards for outstand- ing poster and oral presentations are lauded. In recognition of the students’ achievements, ASBMB has provided funding for many of the awards in the areas of biochemistry and molecular biology. To improve our effectiveness, several signifi- cant steps were undertaken for this year’s meet- ings. First, the MAC has funding for a significant number of complimentary student memberships. These memberships are intended to bring students into ASBMB. It is expected that in the short term these students would form Undergraduate Affiliate Network chapters, apply for travel awards, attend and present at our annual meeting, and participate in the Undergraduate Poster Competition. Such steps would all enhance their undergraduate educa- A Native American performer at a 2006 SACNAS Conference cultural event. tion. In the long term, we expect that these students PHOTO CREDIT DALE HAMEISTER PHOTOGRAPHY. would continue their memberships and eventually become full members of ASBMB. Attendance at both meetings is driven by the desire to Also for this year’s meetings a new booklet, titled Diver- increase the visibility of our professional society, and MAC sity Provides the Answer: Unlocking Life’s Secrets, was distrib- members spend much of their time proactively visiting stu- uted. This attractive, full-color, 12-page handout describes dents at their posters and meeting with the other exhibitors. the career opportunities in biochemistry and molecular During those visits, we introduce students to ASBMB spon- biology and provides insights into how students may best sored student activities and the benefits of membership, prepare themselves for the many educational and profes- and distribute the appropriate literature. Students are also sional challenges that lie ahead. If you or your students recruited to participate in ASBMB’s Annual Meeting and would benefit from these materials,p lease request them via are encouraged to submit abstracts for the Undergraduate [email protected] or download the PDF version Poster Competition and to apply for travel awards. Commit- from www.asbmb.org/minorityaffairs. tee members also expend considerable effort visiting with By the time these meetings are over, attendees are both the directors of the students’ training programs to explain exhausted and energized. They return to their home institu- the benefits of membership—not only what ASBMB can do tions with renewed focus and drive and are better prepared for them but also how their membership will help drive the to deal with their educational pursuits. We look forward to agenda in future years. Overall, ASBMB is showcased in the attending and participating at these, and similar, meetings for hope of establishing a relationship with the student and thus many years to come!
November 2007 ASBMB Today 17 2008
DNA & RNA Biology Molecular Cell Systems Genome Dynamics: RNA-Mediated Structure & Metabolism Replication, Recom- Gene Expression & Dynamics bination and Damage Metabolism Response Protein Synthesis and Turnover
Small RNAs and Systems Biology Dynamic RNA Dynamic Chromatin Elements and Gene Expression Form and Function of Molecular Machines
Cell and Organelle Dynamics Biomolecular Catalysis, Folding and Design Travel Awards s 'RADUATE0OSTDOCTORAL 4RAVEL !WARDS s 'RADUATE -INORITY 4RAVEL !WARDS s 5NDERGRADUATE 3TUDENT #OMPETITIVE 4RAVEL !WARDS s 5!. &ACULTY