ASBMB Announces 2009 Award Winners

August 2008

The Shape of DNA

American Society for Biochemistry and Molecular ),#''' KX^^\[FI=:cfe\j `eZcl[`e^k_\fe\jpflnXek

Kil\FI=  ]fikX^^\[gifk\`e\ogi\jj`fe E$KX^ j :$KX^ j $9CB $9KB $9CB ž ž ž $9CB ž Kil\FI=\eXYc\jk_\\ogi\jj`fef]k_\\eZf[\[kiXejZi`gkXjX ž ?`j$?8$9CB ?8$9CB DpZ$=C8> DpZ$=C8> :$k\id`eXccpkX^^\[gifk\`en`k_DpZXe[=C8> \g`kfg\j#]XZ`c`kXk`e^ ?`j$=C8> >=G ?8$9CB DpZ$=C8> ?`j$?8$9CB dlck`gc\Xggc`ZXk`fejk_Xklk`c`q\XeXek`$kX^Xek`Yf[p#jlZ_Xj Xek`$?`j gifk\`e[\k\Zk`fe#gifk\`egli`ÔZXk`fe#jlYZ\cclcXicfZXc`qXk`fe#\kZ% Xek`$?8 >\efd\$n`[\Zfm\iX^\ Xek`$DpZ J\hl\eZ\m\i`Ô\[Xe[^lXiXek\\[ K_\:$k\id`eXc[lXckX^f]DpZXe[=C8>ž Xek`$=cX^ KiXej]\Zk`fe$i\X[p1Gifm`[\[Xj('l^f]gli`Ô\[gcXjd`[ Xek`$9KB

K_\N\jk\ieYcfkXeXcpj`jf]? `jXi\^`jk\i\[kiX[\dXibf]J`^dX$8c[i`Z_ 9KBkX^^\[n`k_`e[`ZXk\[\g`kfg\j% ($///$)-.$++*-›fi`^\e\%Zfd

ORG-027-ORFSketchV7.indd 1 1/24/08 4:45:45 PM contents August 2008 On the Cover: Karen Vasquez unwinds the society news mysteries of unusual DNA structural variants that 2 From the Editor contribute to genome 3 President’s Message instability, recombination, and gene expression. 5 Washington Update 7 ASBMB Announces 2009 Award Winners special interest 10 Academic Freedom Is a Good Thing, Right? 12 Hungry for Your Data to Tell the Story? Come to the Table! 2009 meeting Thematic Overviews: 14 Chromatin Regulation 16 Gene Regulation 18 RNA: Processing, Transport, FASEB’s 4th Annual Hill Day. 5 and Regulatory Mechanisms 20 Genome Dynamics science focus 30 Karen Vasquez: Understanding Genome Structure and Stability departments 6 News from the Hill 8 Member Spotlight 22 Minority Affairs 24 Education and Training Expand Your Nuclear Horizons. 28 26 Career Insights 28 BioBits resources 34 Career Opportunities podcast summary Hear about the latest research published 36 Scientific Meeting Calendar in the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics on the ASBMB AudioPhiles podcasts at: www.asbmb.org/interactive.aspx.

August 2008 ASBMB Today 1 firstsecond from words the editor A monthly publication of The American Society for Biochemistry and Molecular Biology Focus on DNA Officers By Nicole Kresge Gregory A. Petsko President Heidi E. Hamm Past President Mark A. Lemmon Secretary Merle S. Olson Treasurer his issue of ASBMB Today is chock full of DNA- Council Members Trelated content. We have four articles that look at Dafna Bar-Sagi Alan Hall John D. Scott what’s in store for attendees of the 2009 ASBMB Annual Joan A. Steitz Ann M. Stock Kevin Struhl James A. Wells Meeting in New Orleans who are interested in DNA and Ex-Officio Members nuclear research. First, Ronen Marmorstein and Trevor Archer Ellis Bell tell us all about what we can expect at the Chromatin Regulation Chair, Education and Professional Development Committee theme symposia in their article on p. 14. Some of the highlights Laurie S. Kaguni Chair, Meeting Committee include lectures on genomic approaches to studying the structure and John D. Scott function of chromatin and a look at the proteins that target chromatin Chair, Membership Committee George Hill via histone modifications. Then, Seth Darst and Jesper Svejstrup give Chair, Minority Affairs Committee an overview of the Gene Regulation symposia on p. 16. These talks Kendall J. Blumer Anna Marie Pyle include a lecture on RNA polymerase by Nobel Laureate Roger Co-chairs, 2008 Program Committee Kornberg of Stanford University. On p. 18, Traci Hall and Ben Mary J. C. Hendrix Chair, Public Affairs Advisory Committee Blencowe summarize the talks that will be held under the Toni M. Antalis Chair, Publications Committee RNA: Processing, Transport, and Regulatory Mechanisms Herbert Tabor theme. ASBMB member Joan Steitz, who was recently Editor, JBC Ralph A. Bradshaw awarded the Albany Medical Center Prize (the nation’s A. L. Burlingame richest prize in medicine and biomedical research; p. Co-editors, MCP Edward A. Dennis 8), will be giving a talk titled RNPs: Versatile Regulators Joseph L. Witztum of Gene Expression in Mammalian Cells. And finally, Co-editors, JLR on p. 20, Wei Yang and Anindya Dutta tell us what we ASBMB Today Editorial Advisory Board Alex Toker can expect in the Genome Dynamics theme, including Chair sessions on genetic approaches to studying replication Greg P. Bertenshaw Craig E. Cameron A. Stephen Dahms Irwin Fridovich and initiation, and the mechanisms of DNA replication, Jonathan Gitlin Richard W. Hanson recombination, and repair. Elizabeth A. Komives Bettie Sue Masters Luke A. O’Neill Duanqing Pei In addition to these four articles, our Science Focus this Carol C. Shoulders Robert D. Wells month on p. 30 profiles Karen Vasquez, an associate professor ASBMB Today in the Department of Carcinogenesis at the University of Texas Nicole Kresge Editor [email protected] M.D. Anderson Cancer Center. Vasquez looks at mechanisms of Nick Zagorski Science Writer DNA damage and repair from the perspective of how DNA sec- [email protected] ondary structures can influence these events. She hopes that she can Nancy J. Rodnan Director of Publications [email protected] exploit her findings to create new strategies for targeted therapies, Barbara Gordon Executive Director such as inducing recombination events in specific regions of DNA. [email protected] We are also pleased to announce that ASBMB Today recently Magazine design & production: Amy Phifer received a 2008 APEX Award for Publication Excellence in For information on advertising contact the category of Most Improved Magazines and Journals. We FASEB AdNet at 800-433-2732 ext. 7157 or 301-634-7157, or E-mail [email protected]. couldn’t have done this without our excellent writers, staff, and designer, and of course, suggestions from you, our readers. So keep sending those thoughts and comments to [email protected]. www.asbmb.org

2 ASBMB Today August 2008 president’smessage It Is Alive* BY GREGORY A. PETSKO

hey’re at it again. Armed with another new idea from understands the science at stake here, Tthe Discovery Institute, that bastion of ignorance, but he opposes stem cell research and right-wing political ideology, and pseudo-scientific claptrap, has publicly supported the teaching of the creationist movement has mounted yet another assault “intelligent design” in public schools. A on science. This time it comes in two flavors, propaganda fascinating subtext to this story is that and legislative. Jindal is reportedly under consideration by Republican presi- The propaganda is in the form of a poorly written, badly dential nominee John McCain as a possible vice-presidential acted movie produced by Ben Stein, an attorney and enter- nominee. Unfortunately, Jindal signed the bill on Monday, tainment figure who once served as a speechwriter for U.S. June 23. He also did so with no public announcement; in fact, Presidents Gerald Ford and Richard Nixon. As if working for no one in the state knew he’d done it until several days later. Nixon didn’t do enough to demonstrate his faulty judgment, The bill is cleverly worded: it states in Section 1C that it he has become an ardent critic of and an advocate “shall not be construed to promote any religious doctrine, for ‘intelligent design,’ which is creationism poorly disguised promote discrimination for or against a particular set of as ‘science.’ He co-wrote and stars in the film Expelled: No religious beliefs, or promote discrimination for or against Intelligence Allowed, which attempts to link evolution to the religion or nonreligion.” In an interview with the conserva- eugenics movement in Nazi Germany and to the Holocaust, tive newspaper the Washington Times (June 12, 2008), Jason and portrays advocates of intelligent design as champions Stern, vice president of the Louisiana Family Forum, insisted of academic freedom and victims of discrimination by the “It’s not about a certain viewpoint. It’s allowing [teachers] to scientific community. The famous evolutionary biologist and teach the controversy.” atheist Richard Dawkins has a spirited attack on the film on Let me say this as clearly as possible, so there can be no his web site (http://richarddawkins.net/). mistake about what I mean: there is no controversy. Just Fortunately, the film is sinking faster than the Lusitania. because a few misguided so-called scientists question the As far as I can discover, it has done less than $8 million in validity of the concept of evolution doesn’t mean there is a ticket sales to date, far less than its cost, and is playing to controversy. There are still some people who believe the earth virtually empty houses in the few theaters that are still show- is flat (there’s even a “Flat Earth Society”), but that doesn’t ing it. Whether this is because people recognize it as rubbish mean that a grade school science teacher should teach his or or because it is simply a bad movie, I don’t know. So we can her students that the earth might be flat. The fact that some probably ignore it, as it so richly deserves to be. But the legis- people believe nonsense does not give that nonsense scientific lative attack is much more serious. credibility. A challenge to existing scientific principles must On June 11, 2008, the Louisiana House of Representa- be based on evidence, not on belief, and there isn’t a shred of tives voted 94-3 in favor of a bill that would promote ‘critical evidence to support either creationism or intelligent design. thinking’ by students on topics such as evolution, the origins Those ideas belong in a religion or philosophy class, not in a of life, global warming, and human cloning. The Louisiana science class. Senate had already passed a similar bill, Senate Bill 733, by a (By the way, speaking of religion class, if we accept the vote of 35-0, but an amendment adopted by the House, which creationists’ own rationale for this bill, then shouldn’t right- would allow the state Board of Elementary and Secondary wing fundamentalist Christian schools be forced to “teach Education to prohibit supplemental materials it deems inap- the controversy” about religion? It’s a much more controver- propriate, meant that the Senate had to pass the bill again. sial subject than science. Shouldn’t their students be forced It did. The bill was then sent to Louisiana Governor Bobby to consider the possibility that there is no God, or that the Jindal, at age 36 the youngest governor in the United States Muslim faith, or Hindu faith, or Jewish faith, might be the and the first Indian-American to serve as the head of a state true one? Or that there are so many different translations and government. A former Hindu who converted to Catholicism versions of the Bible that there is no way of knowing which in high school, Jindal attended Oxford on a Rhodes scholar- one is the “word of God”? You can see how quickly their ship. Jindal was a biology major at Brown University, so he argument breaks down.)

August 2008 ASBMB Today 3 firstpresident’ssecond messagecontinuedcontinued What about the academic freedom argument? If someone pupils understand, analyze, critique, and review in an objec- wants to teach creationism in a science class, shouldn’t they tive manner the scientific strengths and scientific weaknesses have the right to do so? Certainly–if they want to get fired. of existing scientific theories pertinent to the course being Because if they do that they deserve to get fired. It has noth- taught.” And in Texas (why is it not a shock that the state that ing to do with academic freedom; it’s about basic competence. gave us George W. Bush would also give us this), the Texas Consider, for example, a science teacher who taught that State Board of Education is again considering mandating a the sun revolves around the earth. Even the intelligent design science curriculum that teaches the “strengths and weak- advocates would probably have to admit that such a science nesses” of evolution. On June 7, 2008, the Houston Chronicle teacher was incompetent and ought to be dismissed. That wrote that “strengths and weaknesses” language is “a ‘teach teacher might counter with a claim that his or her academic the controversy’ approach, whereby religion is propounded freedom was being infringed, but no court would uphold it, under the guise of scientific inquiry.” The editorial went on to any more than a court would uphold a similar claim from a say: “What students really need is to be able to study science history teacher who taught that the Allies lost World War II from materials that have not been hijacked by creationists or that Napoleon Bonaparte was King of Japan. Science, and whose personal agenda includes muddying the science cur- history, may welcome speculation but the speculation must riculum. Creationism is not a ‘system of science’.” be based on facts, and when it isn’t, then it doesn’t belong in As scientists we need to join such protests with our that subject. Any “science” teacher who teaches that the earth feet and wallets. The ASBMB Annual Meeting is sched- might have been created about 6,000 years ago and that all the uled to take place in New Orleans in April 2009. We have material evidence that it’s billions of years old is controver- longstanding contractual obligations that require us to sial is simply incompetent. If the state of Louisiana wants its meet in Louisiana next spring. But I think we need to children taught by such people then they deserve the kind of see to it that no future meeting of our society will take workforce and citizenry they are going to get. place in Louisiana as long as that law stands, nor should It’s worth pointing out that in 1987, in the case of Edwards we hold it an any other state (are you listening, Michigan v. Aguillard, the U.S. Supreme Court ruled as unconstitutional and Texas?) that passes a similar law. And I call upon the idea of equal time for creation science and evolution in the presidents of the American Chemical Society, the biology classes. That precedent will almost certainly be used American Association of Immunologists, the Society for as the basis for a constitutional challenge to the Louisiana law. Neuroscience, and all the other scientific societies around Also, in the state of Pennsylvania, the Kitzmiller v. Dover Area the U.S. and the world, to join me in this action and make School District case in 2005 put to rest the idea of intelligent clear to the state legislators in Louisiana, the governor design as an alternative to evolution being taught in biology of the state, and the mayor and business bureau of New classes. Although not a Supreme Court case, this decision was Orleans that this will be the consequence. You can do the strong enough to cause creation science advocates to switch same. Governor Jindal can be reached through his website tactics to arguments about academic freedom, the focus of (www.bobbyjindal.com/) and so can Mayor Ray Nagin the current legislation at issue in Louisiana. (www.cityofno.com/Portals/Portal35/portal.aspx). Lest you think this is merely some Bible Belt aberration, In its ability to rise again just when we think we’ve let me assure you that the creationists are marshalling this got it licked, creationism is like Frankenstein’s monster. argument in other states as well. In Michigan, Senate Bill “Come see, villagers! It is alive!” We’ll never be rid of it by 1361, introduced in the Michigan Senate on June 3, 2008, being silent and doing nothing, so it is important to force and referred to the Senate Committee on Education, is governments that fall prey to this monster to pay for their yet another “academic freedom” bill aimed squarely at the folly by denying them our business. In addition, we must teaching of evolution. Identical to Michigan House Bill 6027, all arm ourselves with the one weapon we have that in which is still in the House Committee on Education, SB the end the monster cannot overcome: the truth. All of us 1361 would, if enacted, require state and local administra- need to familiarize ourselves with the facts of evolution so tors “to create an environment within public elementary and that we can mount a spirited defense against the forces of secondary schools that encourages pupils to explore scientific ignorance and the charlatans who would exploit human questions, learn about scientific evidence, develop critical insecurity and need for certainty. Carl Sagan memorably thinking skills, and respond appropriately and respectfully called science “a candle in the dark.” Well, the darkness is to differences of opinion about controversial issues” and always around us, closer than you think sometimes. Yes, “to assist teachers to find more effective ways to present it is alive. It’s alive because some of our fellow men and the science curriculum in instances where that curriculum women keep it alive. In the dark. addresses scientific controversies” by allowing them “to help *Reprinted with permission from Genome Biol. (2008) 9, 106 with minor updates.

4 ASBMB Today August 2008 washington update FASEB FASEB Holds Its Fourth Annual Hill Day BY JENNIFER A. HOBIN

ixteen members of FASEB’s Board and Science its version of the bill. Together, these efforts generated SPolicy Committee (SPC), including ASBMB mem- over 3,300 emails, letters, and telephone calls and sent bers Robert Palazzo and Kenneth Mann, participated a strong message to Congress that biomedical research in FASEB’s fourth annual Hill Day on June 3. Joined by should be a national priority. FASEB-society staff, participants visited 13 Congres- This push for additional science funding proved to sional offices on both sides of the aisle, including the be a success: on June 19, after months of negotiation, Senate Committee on Health, Education, Labor, and the Senate approved the House version of the bill by an Pensions and the Senate Subcommittee on Labor, overwhelming vote of 92 to 6. The final legislation, which Health, and Human Services (LHHS) Appropriations. was signed into law by President Bush four days later, The group also visited the offices of Senators Lamar provided an additional $150 million for NIH, $62.5 million Alexander (R-TN), Sherrod Brown (D-OH), Hillary Clinton each for NSF and DOE, and $150 million for the Food (D-NY), Robert Menendez (D-NJ), Patty Murray (D-WA), and Drug Administration. Barack Obama (D-IL), Bernard Sanders (I-VT), Richard While FY 2008 appropriations were wrapping up at the Shelby (R-AL), and Arlen Specter (R-PA), as well as time FASEB met with Congress, budget negotiations for those of Representatives Cliff Stearns (R-FL) and Jim FY 2009 were just beginning. Hill Day participants took Cooper (D-TN). the opportunity to ask their Members to support a $59.7 The meetings provided FASEB society scientists with billion FY 2009 budget resolution for Function 550, the a chance to talk with their members of Congress about budget account that finances Public Health Service agen- their research, the contributions biomedical research cies, including NIH, Centers for Disease Control, and the funding makes to their states, and the negative impact Health Resources and Services Administration. Partici- that flat science funding is having on the research pants also asked Congress to provide $31.1 billion for enterprise. In addition, with both the House and Sen- NIH in next year’s LHHS appropriations bill. Although there ate negotiating major spending bills, participants took is a long way to go in the FY 2009 budget process, there the opportunity to thank those Representatives who has been a strong show of support for science funding have championed biomedical research funding and to so far. On June 26, the Senate Appropriations Committee encourage others to do the same. FASEB leaders were approved an LHHS package that includes $30.3 billion particularly grateful to the Senators who supported the for NIH, a 3.5% increase over the FY 2008 funding level. fiscal year (FY) 2008 emergency spending supplemental The House Appropriations Committee has yet to approve appropriations bill. With a vote on the bill pending in the its own version of the bill, although in its present form it House, they encouraged their Representatives to back includes $30.4 billion for NIH. the legislation as well. Although science funding was a priority issue dur- Seen as the last opportunity to increase FY 2008 ing FASEB’s Hill visits, it was not the only topic on the funding for the National Institutes of Health (NIH), agenda. Participants also took the time to thank Mem- National Science Foundation (NSF), and Department bers who voted for the passage of the Genetic Infor- of Energy (DOE), passage of the supplemental bill had mation Non-Discrimination Act (GINA). This legislation, been a high priority for FASEB. In May, with the Sen- which protects individuals against the misuse of their ate poised to vote on the bill, FASEB President Robert genetic information in health and employment decisions, Palazzo sent letters to every Senator asking them to passed unanimously in the Senate and was signed into support the supplemental and “the lifeline it provides to law on May 21. scientific research.” FASEB also issued an e-action alert calling on scientists across the country to contact their Jennifer A. Hobin is a Senior Science Policy Analyst for the Senators in support of the legislation. The same two- Office of Public Affairs at the Federation of American Societies pronged advocacy strategy was adopted in the days for Experimental Biology (FASEB). She can be reached at before the House voted on, and ultimately approved, [email protected].

August 2008 ASBMB Today 5 news from the hill Finally, Some Good News on Appropriations BY PETER FARNHAM

2008 supplemental appropriations bill with some sci- also said “I don’t think it’s a good bill.” Overall, the bill is Aence funding, and increases in other science agency $7.2 billion more than the President indicated he would budgets as 2009 appropriations bills begin to move, accept. The full appropriations committee approved the bodes well for science funding in the waning days of the bill on June 26. Bush Administration. The bad news is that it is very much Conflict of Interest Addressed an open question as to whether the increases will occur in Senate Report Language before next spring. An interesting side note in the Senate bill is rather opaque Supplemental Signed report language that seems to focus on conflict of inter- President Bush signed the so-called “war supplemental” est in biomedical research funding. The HHS Secretary funding bill on June 30. This bill contains $162 billion in is required to seek public comment on draft regulations funding for the Iraq/Afghanistan conflicts, as well as about “strengthening federal oversight and identifying enhance- $350 million in funding for several science agencies, ments of policies, including requirements for financial including the National Institutes of Health ($150 million) disclosure to institutions, governing financial conflicts of and the National Science Foundation ($62.5 million). The interest among extramural investigators receiving grant Department of Energy’s Office of Science and NASA also support” from NIH. received $62.5 million each. We are not sure what this means but will keep you ASBMB (on its own and as part of various coalitions) informed as the regulations are developed. contacted its 2,000-strong Local Activists Network who On June 19 the House L/HHS Subcommittee contacted their own Members of Congress and senators approved a slightly larger increase for NIH ($1.150 billion, in turn. We have been told by informed members of the about 3.9%) than the Senate, but during full committee congressional staff that without a push from scientists, markup on June 26 partisan wrangling broke out over the the science funding would never have been included in Interior appropriations bill (also being considered during the bill. We encourage any ASBMB member who is not a the same markup session), and Chairman Dave Obey member of the LAN to contact the ASBMB Public Affairs (D-WI) abruptly adjourned the hearing. Obey, famously Office and become one. bad-tempered, then threatened to halt the entire appro- priations process, implying that he would resort to use of 2009 Appropriations Bills— a continuing resolution to fund the government through Net Pluses for Science Funding the fall elections and into 2009. Regardless of whether The good news for science funding continued into late Obey makes good on the threat, the bill will not be con- June as the FY 2009 appropriations bills began progress- sidered until mid-July. ing through the Congress. NIH, NSF, and VA medical A continuing resolution was already a real possibility research all saw increases early on. before Obey threatened one. Informed observers believe Regarding NIH, the Senate Appropriations Subcom- that it is unlikely that the L/HHS bill will go to the Presi- mittee on Labor/HHS and Education marked up its bill on dent for his signature before the November election, thus June 24 and approved $154 billion for FY 2009. $1 billion mandating a continuing resolution at least into the new would go to the NIH, approximately a 3% increase over year and possibly until March, when a new Congress FY 2008. Total funding for NIH would thus rise to $30.2 and President will be in office. The only way this can be billion. Subcommittee chair Tom Harkin (D-IA) said the avoided is if the President has lost enough support in the increase was needed to keep up with biomedical infla- House and Senate to allow vetoes to be overridden. With tion and also to help keep young researchers in science. the conventional wisdom calling for Republican losses in Ranking minority member Arlen Specter (R-PA) welcomed the increase and said it was the best they could do, but continued on page 15

6 ASBMB Today August 2008 asbmb news ASBMB Announces 2009 Award Winners

he American Society for Biochemistry and Molecular The Schering-Plough Research Institute Award will be TBiology (ASBMB) has announced the recipients of its presented to Phillip Zamore, Howard Hughes Medi- annual awards competition. Seven scientists were singled cal Institute Investigator and Professor at the University out for their outstanding achievements and contributions of Massachusetts Medical School. The Schering Plough to science. The awards will officially be presented at the Award was established to recognize young investigators Experimental Biology 2009 Meeting, April 18-22, in New for outstanding research at an early stage of their careers. Orleans. A pioneer in the study of RNA silencing in , Zamore’s laboratory has played a role in nearly all of the David Davies of the NIDDK, National Institutes of major breakthroughs in the study of RNA silencing. Health, will give the Herbert Tabor/Journal of Biological Chemistry Lecture. The award was established to recog- Sandra Schmid, an investigator at the Scripps nize the many contributions of Dr. Herbert Tabor to the Research Institute, will be honored with the William C. Journal of Biological Chemistry and the Society. Davies Rose Award. The award recognizes outstanding contribu- studies the structure and mechanism of action of the tions to biochemical and molecular biological research and Toll-like receptors of the innate immune system as well as a demonstrated commitment to the training of younger other proteins such as anti-anthrax lyase. scientists. Schmid is an internationally recognized bio- , Howard Hughes Medical Institute chemist who has been a pioneer in our understanding of Investigator and Chancellor’s Professor at the University the molecular basis of receptor-mediated endocytosis. of California, Berkeley, will be honored with the ASBMB The ASBMB Award for Exemplary Contributions to Merck Award for his exceptional achievements in and Education will be presented to Rochelle Schwartz- contributions to structural biology. Kuriyan is one of the Bloom of the Duke University Medical Center. The world’s leading researchers on the structure and func- award, administered annually by the ASBMB Education tion of protein kinases, and his studies of c-Src, c-Abl, & Professional Development Committee, is given to a and CaMKII have provided exciting new insights into the scientist who encourages effective teaching and learn- structure and function of molecular systems that are simi- ing of biochemistry and molecular biology through his lar to those found in many other biological contexts. or her own teaching, leadership in education, writing, Sarah Spiegel of the Virginia Commonwealth Univer- educational research, mentoring, or public enlightenment. sity School of Medicine will be presented with the Avanti Schwartz-Bloom’s past research looked at novel pharma- Award in Lipids. This award honors outstanding scientists cologic approaches to preventing neuronal death caused whose research interests are in the field of lipids. Spiegel by cerebral ischemia associated with cardiac arrest and is one of the founders of the paradigm that sphingolipid stroke. Her current research program, which she started metabolites serve as signaling molecules, and the sphin- in 1996, focuses exclusively on science education. golipid signal that she discovered, sphingosine 1-phos- FASEB has also tapped ASBMB member Susan phate (S1P), is now the most thoroughly characterized Lindquist, Howard Hughes Medical Institute Investi- mediator in this field. gator, member of the Whitehead Institute for Biomedi- Douglas Rees, a Howard Hughes Medical Institute cal Research and Professor at the Massachusetts Investigator and Professor of Chemistry at the California Institute of Technology, for its Excellence in Science Institute of Technology, will give the Fritz Lipmann Lecture. Award. The award, given annually by FASEB, recog- This lecture, which is awarded every 2 years, recognizes nizes outstanding achievement by women in the bio- investigators who make conceptual advances in biochem- logical sciences. Lindquist is a pioneer in the study of istry, bioenergetics, and molecular biology. Rees has made protein folding and has shown that changes in protein pivotal contributions to understanding the structure of folding can have profound and unexpected influences integral membrane proteins, membrane transport mecha- in fields as wide-ranging as human disease, evolution, nisms, and metalloenzyme structure and mechanism. and nanotechnology.

August 2008 ASBMB Today 7 asbmb member spotlight Lindquist Honored with Steitz Wins Albany Otto Warburg Medal and Medical Center Prize Stein and Moore Award ASBMB Council member Joan Steitz, Susan Lindquist of the Whitehead Institute Sterling Professor of Molecular Biophysics for Biomedical Research was selected to and Biochemistry at Yale University, has receive the Protein Society’s 2008 Stein and been awarded the Albany Medical Center Moore Award as well as the German Society Prize, the nation’s richest prize in medicine for Biochemistry and Molecular Biology’s and biomedical research. Steitz shares the Otto Warburg Medal. honor with Elizabeth Blackburn for work The Stein and Moore Award, sponsored that has improved disease treatments and by The Merck Company Foundation, was may lead to new ones for degenerative and presented to Lindquist in July at the Protein other age-related disorders. Society’s annual meeting. Lindquist is being honored for her Steitz and Blackburn are the first women ever to receive groundbreaking discoveries in understanding the wide array of the 8-year-old Albany Medical Center Prize. They will share the biological processes governed by protein folding. $500,000 award, which ranks second only to the $1.4 million The Otto Warburg Medal has been awarded by the German Nobel Prize among medical prizes. Society for Biochemistry and Molecular Biology (Gesellschaft für Steitz is known for research that has improved the diagnosis Biochemie und Molekularbiologie, GBM) since 1963. It honors and and treatment of certain autoimmune diseases, including lupus, encourages pioneering achievements in fundamental biochemi- scleroderma, and some forms of arthritis. She discovered the func- cal and molecular biological research. The Medal is regarded as tion of small ribonucleoproteins that play a vital role in producing the highest award for biochemists and molecular biologists in proteins for the body’s most basic biological processes. Germany. The Albany Medical Center Prize in Medicine and Biomedical Lindquist has resolved a variety of difficult problems in biology, Research was established in the fall of 2000 when the late Morris ranging from delineating cellular responses to stress to uncovering “Marty” Silverman announced a gift of $50 million from the Marty genetic variation in evolution. Her work on prions has provided the and Dorothy Silverman Foundation to Albany Medical Center to molecular framework for an extraordinary new form of protein- establish the prize to be given annually for 100 years. based inheritance. Wells Honored at Hendrix to Serve on Research Symposium NIH Council of Councils This past April, Robert D. Wells was Mary J. C. Hendrix, Northwestern University honored at a research symposium entitled, Feinberg School of Medicine, has been “DNA Structure, Mutagenesis, and Human selected to serve as the National Cancer Disease.” Wells, who is currently Director of Institute’s representative to the NIH Council the Center for Genome Research at the of Councils. Hendrix, a former FASEB Institute of Biosciences and Technology, President, also serves ASBMB as chair of its Texas A&M University, Texas Medical Center Public Affairs Advisory Committee. in Houston, was honored for his contribu- The NIH Council of Councils is made tions to science, the Institute of Biosciences up of 27 members selected from the NIH and Technology, and national scientific societies. Institute and Center (IC) advisory councils and advisory commit- Wells is also a past president of the American Society for tees to the NIH Office of the Director. The Council advises the NIH Biochemistry and Molecular Biology and of the Federation of Director on cutting-edge trans-NIH priorities and matters related to American Societies for Experimental Biology (FASEB). the policies and activities of the Division of Program Coordination, The event was attended by between 175 and 250 scientists Planning, and Strategic Initiatives, established by the NIH Reform and participants, including Wells’ past graduate students and Act 2006, and the Office of Portfolio Analysis and Strategic postdoctoral fellows as well as his friends, collaborators, and Initiatives. The Council also acts as an external advisory panel to other associates. the IC Directors during the concept approval stage of the review After the symposium, a dinner was also held for approximately process for trans-NIH initiatives. 115 people. After dinner remarks were provided by Robert J. “My charge to the Council is to be bold and define experiments Schwartz (IBT), Jacquelynn E. Larson (Wells’ technician for 40 years), that engage the community that NIH can do and fund reasonably,” Lorrie Adams (IBT), Julian Davies (University of British Columbia), said NIH Director Elias A. Zerhouni, M.D. “The Council should William R. Brinkley (Baylor College of Medicine), Peter Farnham foster incubation of new ideas and build resources as needed, all (ASBMB), Bettie Sue Masters (University of Texas, San Antonio), and driven by analysis of the science.” John Blaho (MDL Corporation). Following the remarks, Wells recited a poem that he had composed for the occasion.

8 ASBMB Today August 2008 asbmb member spotlight Please submit member-related news to [email protected] Franceschi Given Biological Marnett to Receive Mineralization Award Founders’ Award Renny Franceschi was given the 2008 Lawrence J. Marnett, director of the Biological Mineralization Award at the Vanderbilt Institute of Chemical Biology and International Association for Dental Research Mary Geddes Stahlman Professor of Cancer (IADR) 86th General Session & Exhibition in Research at Vanderbilt University, will receive Toronto, Ontario, Canada this past July. the first Founders’ Award from the American Franceschi is a Professor at the Chemical Society’s Division of Toxicology. University of Michigan School of Dentistry in The award will be presented to Marnett Ann Arbor. He has served as Associate Dean during the fall ACS meeting in Philadelphia. for Research at the University of Michigan Marnett’s research focuses on the role and as president of the IADR Mineralized Tissue Group. He has of the enzyme cyclooxygenase-2 in cancer and inflammation. He published approximately 100 peer-reviewed scientific articles and uses structure-based approaches and medicinal chemistry to is particularly well known for scientific contributions to the field of design selective cyclooxygenase-2 inhibitors as potential anti- mineralized tissue research. inflammatory, cancer-preventative, and antiangiogenic agents. The Biological Mineralization Award, which is supported by Marnett also studies the contribution of normal metabolism to the Unilever Oral Care, is one of 16 IADR Distinguished Scientist generation of DNA damage and mutation. Awards, and it is one of the highest honors bestowed by the IADR. The annual award is given to a member of the division whose The award consists of a cash prize and a plaque and is designed scientific activities have emphasized innovative research in the to stimulate, encourage, and recognize basic research in the field general field of chemical toxicology. The award was established of biological mineralization. to honor the vision and contributions of individuals who worked to get the division started in the mid-1990s. Pawson Honored with Kyoto Prize Anthony J. Pawson, a University of Toronto In Memoriam: professor and a world-renowned cell Rune L. Stjernholm biologist with the Samuel Lunenfeld Rune L. Stjernholm, Professor Emeritus of Research Institute at Toronto’s Mount Sinai Biochemistry, Tulane University School of Hospital, was honored with the 2008 Kyoto Medicine, died peacefully on March 6, 2008 Prize in Basic Science. He will receive a gold in Huntington Beach, California. He was 84 medal and a cash gift of approximately years old. $460,000 at a ceremony in Kyoto, Japan, in Stjernholm was the Biochemistry Chair November. at Tulane from 1971 to 1990 and continued According to the Inamori Foundation, which administers the serving the department as a professor for prize, Pawson received the award for “his proposal and proof of another 13 years. He was an outstand- the concept of adapter molecules, which has established one ing educator who received numerous teaching awards, and his of the basic paradigms in intracellular signal transduction and scientific career was underscored by a prolific record of important contributed significantly to the subsequent development of the discoveries in intermediary metabolism and cancer biochemistry. life sciences.” Stjernholm was born in Stockholm, Sweden, in 1924. He Pawson is best known for his 1986 discovery of the Src received his Ph.D. in 1958 from Case Western Reserve working homology 2 (SH2) domain which binds phosphorylated tyrosine with Harlan G. Wood. He then continued on as a faculty member (pTyr) residues and is essential in cell proliferation, metabolism, at Case Western until 1971, when he moved to New Orleans to and cell-cell communication. This discovery was not only the first assume the Biochemistry Chair at Tulane. identification of what would become the largest class of known During his years in Cleveland and later in New Orleans, he pTyr-recognition domains, it also heralded a new era in protein made several important contributions to our understanding of the science by confirming that proteins were composed of distinct general metabolism of human cells, especially in relation to cancer. modules with specific functions. At Tulane, he built a strong department that distinguished itself The Kyoto Prize, given annually, honors people who have as a cornerstone of medical education and biomedical science at contributed significantly to the scientific, cultural, and spiritual this institution. In addition, he served on a number of community- betterment of mankind in the areas of advanced technology, basic directed organizations that fostered support and excellence in sciences, and arts and philosophy. cancer research in the New Orleans area.

August 2008 ASBMB Today 9 special interest

AcademicBY ANGELA HVITVED Freedom Is a Good Thing, Right?

ost of you probably read ASBMB President Greg …at best, these bills are Petsko’s article on p. 3 about unnecessary and do not theM “Academic Freedom” legislation in Louisiana and the subsequent concern provide any additional over its potential effects on science educa- tion. In case you didn’t, Governor Bobby legitimate protection Jindal signed the “Louisiana Science Edu- cation Act” on June 23 after it overwhelm- ingly passed both houses of the Louisiana legislature. this particular strain of anti-evolution legislation. Although the many groups that sounded the early “Academic Freedom” bills had been introduced in alarm on this legislation are credible proponents of sound several state legislatures in the intervening years since the science education, some members have reasonably asked, Santorum Amendment, but had not made it into law until what is problematic about protecting academic freedom? Governor Jindal signed Louisiana’s at the end of June. This On the surface, it would seem that those devoted to year alone, bills were introduced in Florida, Louisiana, rigorous critical analysis—as most scientists are—would Alabama, Missouri, South Carolina, and Michigan. As of be in favor of legislation protecting the rights of educa- this writing, all have died except Louisiana’s and Michi- tors to discuss controversial or unpopular ideas in their gan’s. The outcome of Louisiana’s is now clear; Michigan classrooms. Unfortunately, things aren’t always what they still has twin bills working through both chambers. seem. Proponents argue the aim of these bills is to protect the The “Louisiana Science Education Act” (SB 733) is one rights of teachers and students to question and critically of several “Academic Freedom” bills introduced in state analyze certain scientific theories; evolution is given as an legislatures this year that trace their lineage to an unsuc- example of one such theory. Supporters claim legal pro- cessful amendment proposed by former Pennsylvania Sen. tections are necessary to allow educators the freedom to Rick Santorum to the original “No Child Left Behind” criticize and discuss scientific issues and encourage “criti- legislation. The Santorum Amendment, as it was called, cal thinking skills, logical analysis, and open and objective was drafted with the aid of the Discovery Institute, a pro- discussion of scientific theories being studied.” intelligent design/creationism think tank, as part of their This year, several of the bills included the phrase “Teach the Controversy” strategy. The goal of this cam- “strengths and weaknesses,” which set off alarms for paign was to provide a legally protected space for teaching some and, in the case of Louisiana, was removed before the “controversies” of evolution by discussing “unresolved final passage. Regardless of the exact wording, most sci- issues” and the “scientific weaknesses of evolutionary the- ence education groups agree that, at best, these bills are ory” in the science classroom. Critics countered that there unnecessary and do not provide any additional legitimate is no controversy as to whether evolution has occurred. protection and, at worst, provide cover for introducing Although you can still find reference to the “Teach the intelligent design and other nonscientific topics into the Controversy” campaign on the Discovery Institute’s web- science classroom. Barbara Forrest, a critic of intelligent site, it appears to have been supplanted by a newer strat- design and expert witness in Kitzmiller v. Dover Area School egy, “Free Speech on Evolution” (which ties in nicely with District, is also a professor of philosophy at Southeastern the theme of Ben Stein’s movie Expelled and the proposed Louisiana University. She helped organize a grassroots legislation in various states). Regardless of the strategy du group, the Louisiana Coalition for Science, publicly jour, there is a well established link between the Discovery opposed to passage of SB 733 and has posted an excellent Institute’s Center for Science and Culture and the push for deconstruction of the bill on their website (see box).

10 ASBMB Today August 2008 special interest

AcademicBY ANGELA HVITVED Freedom Is a Good Thing, Right?

best science. I don’t and, at worst, provide cover for want them to be—I introducing intelligent design don’t want any facts or theories or explana- and other nonscientific topics tions to be withheld from them because of into the science classroom. political correctness.” In a somewhat surprising move, Louisiana’s bill was introduced by State Senator Bill Governor Jindal signed the bill into law on June 23 with- Nevers on behalf of the Louisiana Family Forum, a group out a public announcement. It was not known until a June associated with James Dobson’s Focus on the Family and 26 press release from his office listed it as one of 75 bills the Family Research Council. Nevers, who chairs the that the Governor had recently signed into law. It seems Senate’s education committee, is on the record as stating an odd tactic to take; waiting the 20 days would have “scientific data related to creationism should be discussed accomplished the same objective, without actively taking when dealing with Darwin’s theory.” (Hammond Daily a role in its passage. As of this writing, there had been no Star, April 6, 2008.) In addition to the “protections” out- public comments by the Governor’s office other than a lined above, SB 733 also provides for the use of supple- one-sentence summary in their press release. Civil liber- mental materials when discussing the scientific theories ties and science education groups have vowed to monitor listed. These materials could be, but are not required to the implementation of this legislation very closely. Most be, reviewed by the Board of Elementary and Secondary agree that discussion concerning Louisiana’s new “aca- Education, although the criteria for review are not stated. demic freedom” law has only just begun. On June 11, Louisiana’s House passed SB 733 by a vote of 94 to 3. The Senate had requested two amendments, Angela Hvitved is currently the ASBMB science policy fellow specifying the scientific theories covered and requiring and can be reached at [email protected]. that educators present material from the standard text prior to introducing supplemental materials, forcing it back to the Senate where it passed on June 16 by a vote of Resources 36 to 0. Like many policy issues, the context and implications of After the bill passed both chambers, there were essen- “academic freedom” legislation are complicated. Below tially three options for Governor Jindal: sign it into law, are several links to additional resources for those who wish to read more. veto it, or wait 20 days after which it would automatically become law. Governor Jindal, who has a bachelor’s degree • Full text of Louisiana’s bill (SB 733): www.legis.state. la.us/billdata/streamdocument.asp?did=482728 in biology from Brown, did not announce his intentions when the legislation came to his desk, but past statements • Barbara Forrest’s analysis of SB 733: www. lasciencecoalition.org/docs/Forrest_UpdatedAnalysis_ about creationism and intelligent design were cause for SB_733_6.5.08.pdf concern. On June 15, he appeared on CBS’s Face the Nation • The National Center for Science Education: stating: “I personally think that life, human life and the www.ncseweb.org/ world we live in, wasn’t created accidentally. I do think • Wikipedia entry on Academic Freedom Bills: that there’s a creator… I do think that God played a role in en.wikipedia.org/wiki/Academic_Freedom_bill creating not only earth but mankind. Now, the way that he did it, I’d certainly want my kids to be exposed to the very

August 2008 ASBMB Today 11 publishing series Hungry for Your Data to Tell the Story? Come to the Table!

f a picture is worth a thousand words, then surely a This article is sixth in a series on publishing your table is worth at least half that. When should you add research in the Journal of Biological Chemistry. The a table to your manuscript? Tables should be used to series will address a variety of issues that authors may Ipresent data that cannot be conveyed concisely in text or have when writing and submitting articles to the JBC. a figure. Tabular material is often preferable if you want The articles are written by Cadmus Communications, a to compare and contrast data. If you have large amounts Cenveo company, which is responsible for the editing, of data or precise numeric values, these may be presented production, and printing of JBC articles. more clearly in a table. Data that will likely be calculated (for example, adding the column of percentages to equal

Figure One

12 ASBMB Today August 2008 publishing series

Figure TWO short explanatory legend may precede the table. Col- umn headings (boxheads) should refer to the data immediately below in the column. Straddle headings span two or more columns and can only be used if there are at least two sub- headings (Figure 1). Units of measure should be dis- played under the rule and directly above the numeric values (Figure 2). For the stub column 100%) are often best presented (leftmost column of table) in a tabular format. All data the terms used refer to should be presented in an orga- If a picture values read horizontally nized, easy to read format. The across the table. If there are table should be kept as simple is worth a subentries, then the main as possible: the more complex entries are boldface (see the table, the greater the need Figure 1). If no information for logical organization. The thousand is available for certain cells, JBC avoids dividing tables into it is preferable to leave the parts A and B. Please number words, then space blank; a dash may be as Tables 1 and 2, using Arabic used, but please explain it in (not Roman) numerals. a footnote. Tables may be prepared by surely a table Footnotes are indicated authors in a variety of ways, but by superscript letters and using the table feature in Micro- are permitted for clarity of soft Word is probably the best is worth at information not already way. Many alignment problems provided in the table. Non- are resolved by using Word’s least half that. standard abbreviations that table creation feature. Don’t are used in the table only want to use Word’s table feature? That’s okay, but remember (not already defined in the text) must be defined in a foot- that consistency is the key to a well formatted table. If you note. Your table should be uploaded to Cadmus as part of use the space bar in one column, then the tab key in a second the Word text document. column, and then a comma to separate data in the third Large tables containing complicated information may column, the alignment of the information in the finished best be suited to be presented as supplemental material. table may not come out as you expected. Extra or blank rows You will find this particularly useful for those tables that and columns may also throw off the alignment of your data are more than one page in length. The supplemental data within the table. Tables created in Excel will be converted to appear in the on-line version of the JBC, not the print Word before copyediting. Again, avoid extra or blank rows version. A link within the PDF of your article will take and columns. Think of your table as a grid. Include only one the reader to the cited supplemental material. If the edi- piece of information in each cell. Alignment of information tor agrees during the review process that a table can be can make a huge difference in the reader’s understanding (or supplemental, it is not necessary to upload it to Cadmus. misunderstanding!) of your message. The supplemental material will be posted online by the The table title should be a short phrase. If necessary, a JBC Office exactly as you have submitted it.

August 2008 ASBMB Today 13 2009 annual meeting Chromatin Regulation BY RONEN MARMORSTEIN AND TREVOR ARCHER

he eukaryotic genetic information is packaged into proteins that ensure the proper Ta compact form called chromatin, which contains assembly of the histone proteins nucleosome core particles with DNA wrapped around two within chromatin. Ming-Ming copies of each of the four histone proteins, H2A, H2B, H3, Zhou (Mount Sinai School of and H4. Because of this tight association between DNA Medicine) will explain studies on and histone proteins, all DNA-mediated activities, includ- the structure and biochemistry Archer ing transcription, replication, recombination, and repair, of histone targeting modules, occur in the context of chromatin; nature has evolved an including the acetyl-lysine elaborate and coordinated system to mediate such DNA recognizing bromodomain and transactions. domains associated with E3 Chromatin regulatory proteins can be grouped into ligase activity. Sepideh Khoras- three broad categories as follows: ATP-dependent anizadeh (University of Virginia) chromatin remodeling enzymes that physically move will describe structural studies the histone proteins about the DNA; post-translational on the chromodomains that modification enzymes that covalently modify histones, target lysine-methylated histone chromatin-targeting proteins, or modules that recruit tails as well as nucleic acids proteins to the DNA, histones, or modified histones; and within chromatin. Paul Kaufman histone chaperone proteins that assemble and disassem- (University of Massachusetts Marmorstein ble histones as well as replace variant histones in chro- Medical School) will discuss matin. The “Chromatin Regulation” theme will cover these biochemical and cellular studies on the histone chap- diverse chromatin regulatory proteins with a focus on how erone proteins and how their functions are coordinated they coordinate their distinct activities to modulate varied with other chromatin regulatory activities such as histone biological processes, including their misregulation in many acetylation. human diseases. The “Chromatin Remodeling” session will explore the The “Histone Modifications” session will look at the enzymes and mechanisms that disrupt histone-DNA enzymes that post-translationally modify the histone pro- contacts and change the architecture of chromatin. Jerry teins. Ray Trievel (University of Michigan Medical School) Workman (Stowers Institute of Medical Research) will look will describe studies on the structure and mechanism of at the functions of histone-modifying complexes (HATs, the protein-lysine methyltransferases as well as the dem- histone deacetylases, histone methyltransferases, and ethylase enzymes. Shelley Berger (The Wistar Institute) will histone demethylases) in the processes of chromatin discuss biochemical and cellular studies to probe how dif- remodeling for preinitiation complex formation at pro- ferent histone and non-histone protein modifications work moters as well as during transcription elongation. Geeta in coordination to regulate normal processes within the Narlikar (University of California, San Franciso) will detail nucleus, such as transcription. Ronen Marmorstein (The biophysical and structural approaches to understand how Wistar Institute) will explain the structure and chemistry of chromatin remodeling machines couple the energy of histone acetyltransferases (HATs). Interestingly, although ATP to alter nucleosome structure. Finally, Trevor Archer these enzymes were the first histone modifiers to be bio- (NIEHS, National Institutes of Health) will explore the ability chemically characterized well over a decade ago, current of chromatin remodeling complexes to function in concert studies of these enzymes are still revealing new secrets with transcription factors within chromatin. Collectively, about the diversity of HAT function. these presentations will explore the diversity of enzymatic The “Chromatin Recognition and Assembly” session will activities required for regulated gene expression from address the proteins that target chromatin through native chromatin. and modified histone targets and the histone chaperone The “Genomic Chromatin” session will delve into the

14 ASBMB Today August 2008 2009 annual meeting

Chromatin Regulation Symposium: Symposium: Symposium: Symposium: Histone Modifications Chromatin Recognition Chromatin Remodeling Genomic Chromatin • Structural Basis of Protein and Assembly • Mechanisms of ATP- • Characterization of Lysine Methylation, • Molecular Modulation dependent Chromatin Mammalian Epigenomes, Ray Trievel of Epigenetic Gene Remodeling Enzymes, Keji Zhao • The Complex Language of Transcription, Geeta Narlikar • Nuclear Dynamics and Histone and Factor Post- Ming-Ming Zhou • Protein Complexes Genome Plasticity, translational Modifications • Recognition of Lysine- That Modify Chromatin Geneviève Almouzni in Genomic Regulation, methylated Histone H3 Tail, for Transcription, • Nucleosome Positioning, Shelley Berger Sepideh Khorasanizadeh Jerry Workman Jonathan Widom • New Surprises in • Chromatin Assembly and • To be Announced, Histone Acetylation, Modification, Paul Kaufman Trevor K. Archer Ronen Marmorstein

explosion of information revealed by the application of University) will show that the genomic DNA sequence powerful genomic approaches to the structure and func- of yeast is predictive of the in vivo locations of most tion of chromatin. Keji Zhao (NHLBI, National Institutes nucleosomes, discuss the molecular basis by which of Health) will describe the genome-wide changes of nucleosome positions are encoded, and examine how chromatin modifications that accompany differentiation the encoded nucleosome positions facilitate specific of hematopoietic stem cells to erythroid precursor cells. functions. Geneviève Almouzni (CNRS/Institut Curie) will report on These principal seminars will be complemented with the way DNA is packaged into chromatin within the cell short talks selected from submitted abstracts in the area nucleus and its relevance for chromatin function with of chromatin regulation. We anticipate exciting and infor- a focus on histone dynamics during cell cycle and the mative sessions within the “Chromatin Regulation” theme involvement of histone variants and their chaperones. and expect that many fruitful discussions will result from The final presentation from Jon Widom (Northwestern the presentations and associated poster sessions.

News from the Hill continued from page 6 VA Medical Research Gets a Boost—but Still Lags the congressional elections this fall, it is possible that ner- Finally, the Department of Veterans Affairs medical vous GOP lawmakers in tight races will vote against their research programs got a boost on June 24 when the very unpopular (and “lame duck”) President. House Appropriations Committee approved research funding at $500 million. This restores the $38 million the NSF Enjoys Broad Support President wanted to cut, and it provides a net increase Both the House and Senate acted on NSF appropria- of $20 million over 2008 funding. However, this falls tions in mid-June. On June 17, the House Subcommittee well short of the level of funding recommended by the on Commerce, Justice, and Science approved a $6.85 research community (including ASBMB) of $555 million billion budget for NSF for 2009, a $790 million increase for FY 2009. of 2008 (up 13%). The Senate subcommittee followed suit with an identical bill on June 19. This figure is in line with the President’s request for the agency. NSF thus is Peter Farnham CAE is public affairs officer of the Society. one of the bright spots in science funding this year. He can be reached at [email protected].

August 2008 ASBMB Today 15 2009annualmeeting continued Gene Regulation BY SETH DARST AND JESPER SVEJSTRUP

he mechanism of gene regulation has been the focus of for uncovering general themes in Tintense study over the past several decades in both bac- gene regulation. Karen Wassarman terial and eukaryotic experimental systems. Our knowledge of (University of Wisconsin-Madison) the molecular processes governing transcriptional initiation is has uncovered and investigated the

greatly improved, and much attention is now focused on the role of 6 S RNA in the transcrip- Darst regulation of post-initiation events, such as promoter clear- tional reprogramming of bacterial ance, elongation, and termination. Moreover, a more general cells in stationary phase. understanding of the dynamics of gene transcription in cells In the “Initiation: Dynamics of is emerging. The sessions on gene regulation at the ASBMB Transcription” session, the focus will meeting in New Orleans will provide a unique overview of be on exciting new developments in transcriptional regulation, from atomic resolution structures our understanding of the dynamics of RNA polymerases to the dynamics of transcription in living of transcriptional regulation. Previ- cells. ously, it was thought that most, if High resolution structures of cellular RNA polymerases not all, genes were regulated at from all three kingdoms of life are now available, providing the level of recruitment of factors many new clues into their operation. Seth Darst (The Rock- to promoters. Recent results Svejstrup efeller University), Katsuhiko Murakami (Pennsylvania State indicate that this cannot be true. University), and Roger Kornberg (Stanford University) will com- Early work by John Lis showed pare and contrast RNA polymerase structure and function that at the heat-shock inducible genes in the fruit fly, the from , archaebacteria, and eukaryotes (respectively) polymerase is already engaged when the signal to transcribe is in the “Multisubunit RNA Polymerases: Lessons from the received, but this was thought to be the exception. However, Structures” session. Karen Adelman (National Institutes of Health) has shown that The “Initiation: Mechanisms and Regulation” session will this is actually a common regulatory mechanism. John Lis focus on transcriptional initiation. Richard Ebright (Howard (Cornell University) has continued his work on the dynamics of Hughes Medical Institute, Rutgers University) has used single gene regulation at heat-shock loci in Drosophila, most recently molecule methods to probe the behavior of bacterial RNA by the use of by two-photon microscopy in live polytene nuclei, polymerase at promoters. Kevin Struhl (Harvard Medical which makes it possible to reconstruct images of transcrip- School) has primarily used yeast, but also Escherichia coli and tional regulation in living cells. Robert Singer (Albert Einstein human cells, to understand basic mechanisms that underlie College of Medicine) also makes images of transcription in transcriptional regulation in living cells. Recently, this work has living cells by using a locus-specific reporter system, which taken advantage of genome- and proteome-wide approaches allows precise single-cell kinetic measurements of promoter

Gene Regulation Symposium: Multisubunit Symposium: Initiation: Symposium: Initiation: Symposium: Elongation RNA Polymerases: Mechanisms and Dynamics of Transcription and Termination Lessons from the Regulation • Promoter-proximal Stalling • Contending with Structures • Single-Molecule of Pol II Enhances Gene Transcription Obstacles, • Bacterial RNA Analysis of Transcription, Expression, Karen Adelman Jesper Q. Svejstrup Polymerase, Seth A. Darst Richard Ebright • The Dynamic Interplay of • Regulation of Histone • The X-ray Crystal • 6 S RNA Regulation Transcription Factors and Modification and Structure of RNA of Transcription, Chromatin during Gene Transcription by the Yeast Polymerase from Archaea, Karen Wassarman Activation, John T. Lis Paf1 Complex, Karen Arndt Katsuhiko Murakami • Transcriptional Regulatory • Imaging Real-Time Gene • Role of the RNA • To be Announced, Mechanisms in Yeast and Expression in Living Cells, Polymerase Trigger Loop Roger D. Kornberg Human Cells, Kevin Struhl Robert Singer in Transcript Elongation and Transcriptional Regulation, Robert Landick

16 ASBMB Today August 2008 2009annualmeeting continued

binding, initiation, and elongation. describe mechanisms used by cells plays an important role in directing 3’ In the “Elongation and Termination” to ensure that obstacles to transcrip- end formation of nonpolyadenylated session, the focus will shift toward the tion are not allowed to permanently RNA polymerase II transcripts, such as later events of the transcription cycle. block gene transcription. Karen Arndt small nucleolar RNAs. Bob Landick (University of Wisconsin- (University of Pittsburgh) has shown that Besides these principal talks, short Madison) will discuss the regulation the so-called Paf complex has multiple talks will be selected for presenta- of transcription elongation and paus- functions in post-initiation events during tion from submitted abstracts in these ing, and Jesper Svejstrup (Cancer gene transcription, including in co- areas. We look forward to many fruitful Research, UK) will continue on the transcriptional histone modification. Her discussions in the ever dynamic field of theme of transcript elongation and lab has also found that the Paf complex gene regulation.

NNEWEW SSELECTIVEELECTIVE AANTANTAGGONISTONIST ®® -- ONLYONLY FROMFROM AAVANTIVANTI

W146 Many more (S1P1 Antagonist) Avanti Number 857390 (R) Agonists & Antagonists available Visit www.avantilipids.com for details

W140 (S) (S1P1 Control Molecule) Avanti Number 857391

Enhancement of capillary leakage and restoration

of lymphocyte egress by a chiral S1P1 antagonist in vivo. Sphingosine 1-phosphate (S1P) regulates vascular barrier and lymphoid development, as well as lymphocyte egress from

lymphoid organs, by activating high-affinity S1P1 receptors. We used reversible chemical probes (i) to gain mechanistic insights into S1P systems organization not accessible through genetic manipulations and (ii) to investigate their potential for therapeutic modulation. Vascular (but not airway) administration of the preferred

R enantiomer of an in vivo–active chiral S1P1 receptor antagonist induced loss of capillary integrity in mouse skin and lung. In contrast, the antagonist did not affect the number of constitutive blood lymphocytes. Instead,

alteration of lymphocyte trafficking and phenotype required supraphysiological elevation of S1P1 tone and was reversed by the antagonist. In vivo two-photon imaging of lymph nodes confirmed requirements for obligate agonism, and the data were consistent with the presence of a stromal barrier mechanism for gating lymphocyte

egress. Thus, chemical modulation reveals differences in S1P-S1P1 ‘set points’ among tissues and highlights both mechanistic advantages (lymphocyte sequestration) and risks (pulmonary edema) of therapeutic intervention. M Germana Sanna, Sheng-Kai Wang, Pedro J Gonzalez-Cabrera, Anthony Don, David Marsolais, Melanie P Matheu, Sindy H Wei, Ian Parker, Euijung Jo, Wei-Chieh Cheng, Michael D Cahalan, Chi-Huey Wong & Hugh Rosen. Copyright Nature Publishing Group. Published online at http://www.nature.com/naturechemicalbiology Email [email protected] or visit www.avantilipids.com

FROM RESEARCH TO CGMP PRODUCTION - AVANTI’S HERE FOR YOU 2009annualmeeting continued RNA: Processing, Transport, and Regulatory Mechanisms BY TRACI HALL AND BEN BLENCOWE

ollowing the sequencing of whole genomes of sev- present work on the genera- Feral eukaryotic species during the past decade, it tion and function of small became immediately apparent that differences in gene RNAs in Arabidopsis. Phillip Blencowe regulation, and not gene number or repertoire, likely Zamore (University of Mas- account for much of the remarkable functional and sachusetts Medical School) phenotypic diversity among higher eukaryotes. Around will describe the expanding the same time as the completion of these large scale world of small RNA species, projects, an explosion of discoveries revealed the enor- their diverse activities and mous roles played in gene regulation by small RNAs mechanisms of function. and other RNA-mediated regulatory activities. RNA has Adding a different perspec- since taken a center stage in our efforts to understand tive, Henry Krause (Univer- the complex and intertwined mechanisms that contrib- sity of Toronto) will present ute to the myriad of fundamental biological processes. new findings stemming from The extremely rapid pace of discoveries in RNA his group’s recent genome- biology makes it a challenge for any one researcher wide survey of RNA localiza- Hall to keep pace with the many exciting and important tion patterns in Drosophila. discoveries being made. With this challenge in mind, The “RNA Structure and we are delighted to be able to bring together a group Recognition” session will cover a variety of aspects of of leading experts in diverse topics in the field of RNA folding and molecular interactions. Kevin Weeks RNA in an ASBMB-sponsored theme entitled: “RNA: (University of North Carolina) will demonstrate how Processing, Transport, and Regulatory Mechanisms.” chemical probing can be used as a high throughput This theme will feature sessions titled “Ribonucleo- method to examine the structure of very large RNAs, proteins (RNPs),” “RNA Regulation and Transport,” such as viral genomes. Adrian Ferre-D’Amare (Fred “RNA Structure and Recognition,” and “RNA Process- Hutchinson Cancer Research Center) will describe ing.” The invited speakers’ research runs the gamut of how small molecules can modulate the functions approaches, including biochemical, genetic, computa- of ribozymes and riboswitches. Traci Hall (National tional, structural, and cell biological strategies. Institute of Environmental Health Sciences) will illus- The session on RNPs will feature Joan Steitz (Yale trate how both natural evolution and researchers have University), whose discovery of, and continued work tailor-designed Pumilio family proteins for specific RNA on, small nuclear and other RNPs forms the foundation recognition. of the topic of this session. Joining her will be Christine Rounding off the theme, the “RNA Processing” Guthrie (University of California, San Francisco) who session will cover both genome-wide principles and has made pioneering discoveries on the spliceosome focused mechanisms by which transcribed precursor and will be presenting her latest work on splicing RNAs are altered to produce mature, functional RNA regulation in yeast. Maria Carmo-Fonseca (Institute molecules. V. Narry Kim (Seoul National University, of Molecular Medicine in Lisbon, Portugal) completes Korea) will describe the intricate steps required for this remarkable group of speakers and will present her generating microRNAs (miRNAs) from primary miRNA group’s work on the in vivo dynamics of spliceosomal precursors. Benjamin Blencowe (University of Toronto) assembly. will present new work on the regulatory factors that The “RNA Regulation and Transport” session will control alternative splicing in the mammalian nervous highlight research on RNA-mediated gene regula- system. Christopher Burge (Massachusetts Institute of tion and transport and localization of RNA in the cell. Technology) will present a genome-wide view of alter- Xuemei Chen (University of California, Riverside) will native splicing and the regulatory sequences that form

18 ASBMB Today August 2008 2009annualmeeting continued

the underlying code controlling this process. 2008 Interactive In addition to the invited speaker talks, we will include several short talks in the program based on submitted abstracts. These short talks will Annual Meeting help promote young scientists with exciting new results and are expected to complement the main Award Lectures topics of the sessions. We encourage you and your colleagues to submit abstracts for consider- ation. Now Live! We hope that you will enjoy the sessions we have planned for ASBMB 2009, and we look forward to seeing you in New Orleans.

RNA: Processing, Transport, and Regulatory Mechanisms Symposium: Ribonucleoproteins • RNPs: Versatile Regulators of Gene Expression in Mammalian Cells, Joan Steitz • New Insights into the Regulation of mRNA Splicing, Christine Guthrie • In vivo Dynamics of Spliceosome Assembly, Maria Carmo-Fonseca Symposium: RNA Regulation and Transport • Small RNA Diversity and Function, Phillip D. Zamore • Small RNA Metabolism in Arabidopsis, Xuemei Chen • Genome-wide Analysis of Subcellular RNA Trafficking, Henry Krause Symposium: RNA Structure and Recognition • RNA Recognition by PUF Proteins, Traci M. T. Hall • High-throughput Analysis of RNA Structure by SHAPE Chemistry, Kevin Weeks • Ribozymes and Riboswitches: Modulation of RNA Function by Small Molecules, Adrian Ferre-D’Amare Symposium: RNA Processing • Alternative Splicing in the Mammalian Nervous System, Benjamin Blencowe • Global Patterns in Alternative Pre-mRNA Processing, Chris Burge • MicroRNA Biogenesis, V. Narry Kim www.asbmb.org/ 08Awards.aspx 2009annualmeeting continued Genome Dynamics BY WEI YANG AND ANINDYA DUTTA

NA encodes the genetic blueprint of most organ- checkpoint system regulates Disms, so DNA replication and repair are essential to replication in the presence of ensure the continuity of life. Changes in genomic DNA damaged DNA. Fragile sites can give rise to evolution, but changes without checks are specific loci that display and balances may lead to multiple disorders including enhanced frequency of Dutta cancer. The “Genome Dynamics” theme at the 2009 genomic instability, often due ASBMB annual meeting will contain four sessions: to replication fork collapse, “Genetic Approaches to Studying Replication Initiation,” and lead to many genetic “Biochemical Advances in DNA Replication Initiation,” diseases. Ellen Fanning “Mechanisms of DNA Replication, Recombination, and (Vanderbilt University) will Repair,” and “Genomic Integrity and Cancer Biology.” report on results connect- The sessions are organized to showcase the complex- ing chromosomal fragile ity of genome dynamics, timely advances, and the tools sites in mammalian cells to and approaches at the leading edge of research. DNA replication origins and The regulated initiation of DNA replication at replica- preRCs. tion origins is a key process for maintaining genomic The session “Genetic stability. The pre-replicative complex (preRC) binds to Approaches to Studying Yang origins of replication in the early G1 phase of the cell Replication Initiation” will cycle and triggers the firing of replication forks early in focus primarily on genetic S phase. Stephen P. Bell (Massachusetts Institute of techniques used to study the regulation of DNA replica- Technology) and Haruhiko Takisawa (Osaka University) tion. Anindya Dutta (University of Virginia) will describe study replication initiation in cell-free systems from how the genetic manipulation of selected replication yeast and Xenopus, respectively. In the “Biochemical initiation factors in mammalian cells leads to re-replica- Advances in DNA Replication Initiation” session, they will tion of chromosomal segments in the same cell cycle describe advances in how preRCs assemble, how repli- and how this causes genomic instability observed in cation forks begin at origins of replication, and how the cancers. David M. MacAlpine (Duke University Medical

Genome Dynamics Symposium: Symposium: Symposium: Symposium: Biochemical Advances in Genetic Approaches to Mechanism of DNA Genomic Integrity DNA Replication Initiation Studying Replication Repair, Replication, and Cancer Biology • Initiation of Replication Initiation and Recombination • A Multi-protein Complex at a Eukaryotic Origin, • Re-replication and • Repair of DNA Double- Involved in the DNA Stephen P. Bell Its Consequences, strand Breaks and Tumor Damage Response • Initiation at the Fragile Anindya Dutta Suppression, Maria Jasin Network of Fanconi X (FMR1) Origin • The Role of Local • Lesion Bypass in DNA Anemia and Breast Cancer, Weidong Wang of Chromosomal Transcription and Replication, Wei Yang Replication, Ellen Fanning • BRCA1 and DNA Chromatin Structure • Tales from Transposons,

• Chromosomal in Establishing DNA Nancy L. Craig Damage Response, DNA Replication in Replication Origins, Junjie Chen Xenopus Egg Extracts, David MacAlpine • Cancer or Premature Haruhiko Takisawa • The Initiation of Aging in Genome Chromosomal DNA Instability Disorders, Replication in Budding Laura Niedernhofer Yeast, Hiroyuki Araki

20 ASBMB Today August 2008 2009annualmeeting continued

Center) will describe studies from the Hopkins School of Medicine) study cancers result from failure to prop- modENCODE project, which identi- DNA breaks, both programmed and erly repair DNA damage and a sub- fies and characterizes the functional accidental. Their talks will highlight sequent failure to eliminate defective DNA elements that regulate the alternative pathways of processing cells. Junjie Chen (Yale University replication program in a variety of double-strand breaks and the good, School of Medicine) studies the Drosophila cell lines, tissue types, bad, or ugly consequences of DNA breast cancer susceptibility gene 1 and developmental stages. Finally, transposition and recombination. For (BRCA1) and its role in DNA damage Hiroyuki Araki (National Institute of every DNA transaction, a collection checkpoint control. Laura Niedern- Genetics, Japan) will return to the of macromolecules will have to come hofer (University of Pittsburgh School theme of the preRC in yeast, focus- together to form a macromolecular of Medicine and Cancer Institute) ing on how preRCs are activated to assembly and disassemble after uses a mouse model to study the initiate replication at the onset of S the process is complete. Wei Yang DNA repair nuclease ERCC1-XPF phase through the activity of cyclin- (National Institutes of Health) will dis- and identifies strategies to prevent dependent kinases. cuss how she uses structural biology or delay age-related disease without For the session titled “Mechanism to provide a series of snapshots of promoting cancer. Weidong Wang of DNA Replication, Repair, and these macromolecules at work. (National Institutes of Health) studies Recombination,” three scientists Cancer and aging affect length the Fanconi anemia (FA) syndrome. specializing in genetics, biochem- and quality of life. The session titled He will discuss recent work on how istry, and structural biology have “Genomic Integrity and Cancer a macromolecular machine contain- been invited to share their research. Biology” will focus on how defects ing multiple FA and Bloom Syndrome Both Maria Jasin (Sloan-Kettering in genome maintenance accelerate proteins functions in genome main- Institute) and Nancy L. Craig (Johns aging and malignant growth. Many tenance and prevents cancers.

Register for the AAMC Minority Faculty Career Development Seminar! September 12-15 in Alexandria, Virginia This professional development seminar is designed for junior faculty who are members of underrepresented racial and ethnic minority groups and who aspire to leadership positions in academic medicine. For more information go to: www.aamc.org/meetings/minfac/2008/start.htm firstminoritysecond affairs words Health Disparities in Cancer BY JEROME C. NWACHUKWU

health disparity is observed when the health status the highest death rates for prostate cancer and black A of members of certain populations is unequal to the women had the highest death rates for breast cancer. health status of members of other populations. In 1985, Another example of the disproportionate rates of cancer Margaret Heckler, the Secretary of the Department of is observed in Native Americans/Alaska Natives who Health and Human Services, issued the Report of the have the lowest incidence but not the lowest death rates Secretary’s Task Force on Black and Minority Health, of colorectal cancer in both 1999 and 2004. Interestingly, which elucidated severe disparities in health status liver cancer, which is not one of the most common types among Americans of different racial and ethnic groups1. of cancer, has the highest rates in Asian/Pacific Islanders. In this report, disparities against black men and women This type of cancer also had higher rates in blacks, Native were observed in life expectancy and overall death Americans/Alaska Natives and Hispanics, compared with rates, as well as in deaths attributed to several diseases, Whites. Liver cancer incidence and death rates generally including cancer. As a result of this report, the Depart- increased between 1999 and 2004. The presence and per- ment of Health and Human Services created the Office of sistence of such differences indicates a health disparity. Minority Health. Two years later, the Center for Disease One common rationalization often used to explain Control and Prevention followed suit and created its own or perhaps diminish the relevance of these disparities is office, which was later renamed the Office of Minority the de facto correlation between socioeconomic status Health and Health Disparities. and access to good health care in the U.S. However, there The goals of both offices include eliminating health are also cancers, for instance leukemia, lymphoma, and disparities for “vulnerable” populations, and both offices skin cancers, that have lower rates for all four groups have clearly made substantial and progressive efforts compared with whites. Therefore, although low socioeco- toward addressing these disparities. However, this goal nomic status may contribute to these differences, it does has proved to be particularly difficult to attain. not appear to account for the existence and persistence of Today, cancer is the second leading cause of death in such disparities in cancer incidence and death rates. the United States. It is a complex disease characterized by malignant cell proliferation in a wide variety of organs Risk Factors, Prevention & Treatment or primary sites, and often leads to metastasis and tumor The common saying “Prevention is better than cure” is growth at secondary sites. Currently, the American applicable only if “Prevention” is in fact possible. For the Cancer Society keeps track of about 50 different types various types of cancers, the risk factors, growth rates, of cancers. The three most common types of cancers and most-effective treatment options are different. Argu- among whites, blacks, Asian/Pacific Islanders, Native ably, the chances of preventing complex diseases such as Americans, and Hispanics are prostate (men) or breast cancer can be greatly increased through efforts directed (women), lung, and colorectal cancers. at reducing or eliminating the effect of specific risk fac- tors, provided that these risk factors are known. Risk Disparities in Cancer factors for most cancers often include environmental, Health disparities are tracked by three main statistics: developmental, and genetic components. the rate of incidence (i.e. the number of new cancer In cancers where environmental risk factors are cases), the rate of mortality (i.e. the number of deaths known, efforts can be made to reduce exposure to these due to cancer), and the rate of survival (i.e. the length factors. For example, smoking tobacco products can of survival after diagnosis). Although cancer death rates increase the risk of lung cancer; hence it is advisable to have somewhat declined for most populations, there abstain from smoking. In addition, the National Institute are significant differences in both cancer incidence and for Occupational Safety and Health maintains a list of death rates among the different populations. carcinogenic substances which can increase the risk of For example, in 1999 and in 2004, black men had cancer incidence. Therefore, efforts to avoid exposure

22 ASBMB Today August 2008 firstminoritysecond affairs words

to such substances are expected this area within the latter part of to help prevent or reduce cancer A health this century. incidence. However, some cancers are However, the risk factors disparity is resistant to current therapy, and for the most common cancers many others acquire resistance also include developmental and observed when during the course of the disease. genetic factors that are practically the health status In most cases, resistance to unavoidable. For instance, the therapy and/or recurrence even- risk of prostate cancer incidence of members of tually leads to death. Dispari- is known to increase with age. certain populations ties in cancer death rates (e.g. The disease is prevalent in men those observed in breast cancer) over 65 and rare in men under is unequal to the suggest that there are ethnicity- 45 years of age. Furthermore, the related risk factors for death National Cancer Institute now health status of from the disease. Therefore, lists mutations in three genes members of other determining why some cases are (BRCA1, BRCA2, and CHEK2) as more likely than others to recur potential risk factors for breast populations. after therapy is very important cancer. and has become a rapidly grow- For some types of cancers, ing aspect of molecular biology vaccination may provide a viable shot toward prevention. and biochemistry research over the years. Potentially, the For example, human papillomavirus (HPV) infection results of these studies could also help identify specific is a major risk factor for cervical cancer, and in 2006, and reliable risk factors that differentially increase cancer Gardasil, a new vaccine made by Merck & Co., Inc. to death rates among the various populations. prevent infection from four types of HPV (two of which Hence, whereas ethnicity-related differences in socio- are accountable for approximately 70 percent of cervical economic status and known risk factors may contribute cancer cases) was approved by the U.S. Food and Drug to disparities in cancer incidence, they do not completely Administration. Therefore, cervical cancer prevention explain the existence and persistence of health dispari- may have crossed an important milestone, unlike most ties in cancer. So far, current therapies, which have been common cancers, which are not yet understood well somewhat effective in reducing cancer death rates, do enough for scientists to develop drugs to prevent their not seem to be effective in reducing the associated health occurrence. disparities. Perhaps additional efforts should be directed The use of vaccines such Gardasil could also provide toward cancer prevention and identifying reliable risk insight to the efficacy and reliability of vaccinations in factors for cancer deaths to help reduce and eventually eliminating health disparities in cancer. However, once eliminate these disparities in cancer. such cancers have been diagnosed, do additional risk factors that may differentially increase death rates among Jerome C. Nwachukwu is a Ph.D. candidate in the Molecular populations come into play? In other words, could it be Pharmacology Training Program at the New York University that the risk factors for cancer incidence are perhaps School of Medicine Sackler Institute of Graduate Biomedical slightly but significantly different from the risk factors Sciences in New York City. He has served on the ASBMB MAC for cancer deaths? If so, perhaps more efforts should be since 2006 and can be reached at [email protected]. made toward identifying reliable risk factors for can- cer deaths and reducing the effects of these risk factors among various populations. References 1. U.S. Department of Health and Human Services. Report of the Secretary’s Currently, the treatment regimen for common cancers Task Force on Black and Minority Health. Washington, D.C.: U.S. Department includes a combination of surgery, radiation therapy, of Health and Human Services, 1985. 2. U.S. Cancer Statistics Working Group. United States Cancer Statistics: and chemotherapy/hormone therapy. Indeed several 1999–2004 Incidence and Mortality Web-based Report. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control cancer cases are initially responsive to therapy, thanks to and Prevention and National Cancer Institute; 2007. Available at: extensive research and drug development conducted in http://www.cdc.gov/uscs.

August 2008 ASBMB Today 23 education and training The Changing Face of Education in the Molecular Life Sciences BY ELLIS BELL

n the last few years there has been a quiet revolution reads like a who’s who of liberal arts science education, Iin the way we teach undergraduates biochemistry and rewarding schools that have been innovative and successful molecular biology. Fueled by a variety of initiatives by both in the past while at the same time bringing new institutions the Howard Hughes Medical Institute and the National into the mix, such as Gustavus Adolphus College in rural Science Foundation, a focus on undergraduate research has Minnesota, long known for producing outstanding under- become commonplace in the top undergraduate programs graduates in biochemistry and molecular biology. around the country. This focus takes a variety of forms. The schools that received the grants will use a number Some programs focus on summer research experiences, of innovative ways to include research in the undergraduate some on year-round research, and others on incorporating experience. For example, Barnard College will incorporate research into formal course work, all with success. Students “real” research involving studies on pest attacks on tomatoes learn more both in terms of skills and techniques as well and potatoes into its formal laboratory courses, rather than as core knowledge. Project Kaleidoscope for many years the still prevalent “cookbook” approach to labs. Similarly, has been promoting innovative classroom activities and Smith College will move away from “cookbook” teaching training of college teachers to more fully engage students by increasing its focus on experimental and problem-based in the learning process, again with significant achievement. learning, including an innovative new center focusing on Recently a new bill was introduced in the U.S. House of K-12 outreach. Bowdoin College will initiate a program to Representative, H.R. 6104: Enhancing Science, Technol- give its undergraduates an enhanced research experience ogy, Engineering, and Mathematics Education Act of 2008, by providing for 1 to 2 years of full-time research before a “To provide for the coordination of the Nation’s science, student goes on to graduate school. Lewis and Clark College technology, engineering, and mathematics education initia- will combine a variety of student-faculty mentoring oppor- tives” by creating an office to design education programs. tunities. And finally, Swarthmore College will utilize peer Likewise, the Department of Education is creating an office mentoring to enhance the involvement of new students with to work on solving these problems. upper class students. The Government already supports science education Perhaps the most significant aspect of the awards is the through the National Science Foundation by focusing on number of schools that will focus on the creation of interdis- “broader impact” issues in the review of competitive research grants in its various directorates as well as a variety of sci- ciplinary introductory courses to ensure that a new genera- ence education programs aimed at all levels of education, tion of students approach problems from an interdisciplin- administered through the “Education and Human Resources” ary perspective rather than being bound by old traditional directorate. The NSF supports education through investiga- departmental boundaries. For example, in perhaps the most tor-initiated programs, and they are clearly starting to have ambitious project, the University of Richmond will invest sig- an impact in both the research laboratory and the classroom. nificant faculty time from a number of departments to create NIH also has significant educational activities, again at all a two semester interdisciplinary course that will replace the levels. We should be increasing support for such ongoing, standard introductory course in computer science, biology, successful initiatives that harness the creative power of indi- math, chemistry, and physics. vidual investigators rather than creating more infrastructure. A read through of the various descriptions of the pro- HHMI, in its current round of awards to liberal arts col- grams that these 48 schools will create gives the sense that leges, is again pushing the envelope in science education. the future of science education for all students is in good Forty eight liberal arts institutions were recently awarded a hands!

total of $60 million to “identify creative new ways to engage Ellis Bell is Chair of the ASBMB Education and Professional your students in the biological sciences.” The list of awardees Development Committee. He can be reached at [email protected].

24 ASBMB Today August 2008 education and training Postdoctoral Fellows and the Research Enterprise BY LISA M. CURTIS, RASHADA ALEXANDER, JASON RAWLINGS, LU-ANN POZZI, AND JONATHAN GITLIN

ecently, three reports addressing aspects of the research in biomedical research, largely because of the financial sup- Renterprise with relevance to postdocs and their career port of taxpayers’ dollars through the NIH, NSF, and other advancement were released. The effects of decreased federal governmental entities, as well as contributions by research funding of biomedical research in the U.S. in recent years institutions to support the higher education and training of and the particular effects on junior investigators were postdocs. The doubling of NIH funding in the late 1990’s addressed in “A Broken Pipeline? Flat funding of the NIH led to growth in the numbers of positions for postdocs at puts a generation at risk”, a commentary published by a con- research institutions to pursue advanced training. Forward sortium of institutions, as well as in the American Academy thinking regarding the inevitable fluctuations in govern- of Arts and Sciences’ white paper, “Advancing Research in mental funding of research, however, has been lacking at Science and Engineering: Investing in early-career scien- both the governmental and institutional levels. In academia, tists and high-risk, high-reward research”. The effects on increases in the numbers of postdocs advancing to non- the proposal and undertaking of more speculative research tenure track positions or to research associate positions projects in this climate of highly competitive governmen- have increased in the last several years. These types of posi- tal funding were also discussed in the American Academy tions do not hold the same career advancement potential as paper. The 2007-2008 Peer Review Self-Study released by their tenure-track counterparts. Furthermore, the number the National Institutes of Health (NIH) addressed the need of independent funding opportunities for postdocs has not for grants at different career stages and types. It also called kept pace with the increased numbers of them in training for a realistic evaluation of the NIH’s “contribution to the positions. optimal biomedical workforce needs,” and highlighted the As the national advocacy organization for postdocs, need for data-driven analysis of NIH peer-review outcomes the National Postdoctoral Association (NPA) believes that to propose more appropriate changes. this current imbalance needs to be addressed by all stake- These issues, although primarily focused on junior inves- holders. Continued progress in science requires a stable tigators, have significant implications for postdoctoral fel- financial commitment from the NIH, as well as individual lows. The “pipeline” is fed by postdocs, and effects on grant research institutions. Effective solutions for the funding of funding opportunities and career advancement in academia scientific research should address issues beginning with directly impact their career choices and outcomes. the pipeline of investigators at the postdoctoral level and The development of research scholars with strong scien- continuing through to senior investigators who serve not tific and managerial skills is an arduous, time-consuming, only as experienced researchers but also as valuable advisors and expensive effort. More than 70 percent of postdocs in to those more junior. Finally, data collection on profes- the U.S. are supported by federal dollars, and the benefits sional outcomes of postdocs, as well as on their success in of this investment are not reaped when these highly trained acquiring independent grants, is essential to realizing the individuals leave the pipeline. As implied in the NIH’s Self- necessary changes to the scientific enterprise. Implementing Study, the numbers of postdoctoral trainees should reflect responsible revisions to the training and advancement of the future needs of biomedical research. Furthermore, the postdocs will have a direct impact on the long term pros- ability of junior scientists to achieve independent funding pect of scientific research and ensure the U.S. continues to is important not only for professional advancement but also set the bar for the advancement of science. for innovation in science. Stagnation of scientific thought occurs more readily in a climate of fierce competition; study Lisa M. Curtis, Rashada Alexander, Jason Rawlings, and sections are hesitant to invest in riskier explorations. This Lu-Ann Pozzi are members of the Advocacy Committee of risk aversion most directly affects junior scientists. the NPA. Jonathan Gitlin is Vice-Chair of the NPA. All authors Historically, the U.S. has occupied a preeminent position contributed equally to this article.

August 2008 ASBMB Today 25 firstcareersecond insights words Let the Wind be Your Guide: Unexpected Changes in a Science Career BY CHRISTINE LOVE

everal years ago, I read an article control and prevent diseases. Unfortu- Sreporting that up to 60 percent of nately, I found lab work to be isolating people make a career switch in their and monotonous, and I realized that I lifetime. This number seemed low to me, enjoyed discussing research more than considering my own switches and those actually conducting it. of so many of my friends and colleagues. Remembering that several people I’ve always thought it is unrealistic to had told me that I had a knack for expect that young adults entering college explaining complex concepts, I decided Love will truly know what they want to do to augment my biology degree with a with their lives. At 18, I couldn’t even do master’s in communication. Once again, Christine Love is a marketing com- my own laundry! I found myself struggling to decide munications writer for SWCA Envi- Unwilling to join the ranks of those which path to take. There are so many ronmental Consultants in Phoenix, misguided, unfortunate students who career options in the communications Arizona. She has a B.S. in Biology couldn’t choose a major, I declared field, but I resisted straying too far from from James Madison University and myself a biology major during my fresh- my original loves of health and science. an M.A. in Communications from man year. Depending on one’s point of Finally, I decided on a dual concentra- George Mason University. In 2007, view, I was either plagued or blessed tion of health communication and orga- Christine started her own edit- with the desire to go in several different nizational communication. The health ing company, Love Editing, which paths with my degree. Medicine crossed communication knowledge became provides proofreading and editing my mind, but after volunteering as a cer- especially helpful when, several months services for academia, business, tified emergency medical technician and after enrolling in the master’s program, and healthcare. Christine can be embarrassingly passing out on numer- I took a position as a health writer/ reached at [email protected] or ous occasions at the sight of blood, I information specialist for a government [email protected]. decided research was a better fit. contracting firm. It was an exciting After graduating, I embarked on change from the lab environment, and a career as a research assistant at a the position gave me the opportunity to I helped to develop a series of consumer- biotechnology firm in Rockville, Mary- wear many “hats.” targeted HIV fact sheets, and I worked land. The firm specialized in proteom- My department had a contract with as a “behind the scenes” HIV specialist, ics, a discipline analogous to genomics the National Institutes of Health and providing interactive web-based infor- but with a focus on the structure and its subsidiaries. Under this contract, mation to the public. function of proteins. My position my primary responsibility was edit- When my husband’s job required a entailed preparing two-dimensional ing and abstracting protocols for HIV/ cross-country move to Phoenix, Ari- electrophoresis gels for analysis of AIDS-related clinical trials. However, zona, I initially lamented my resigna- proteins as well as developing ideas my role continued to expand, and I tion and distance from all the health and protocols to streamline various began performing similar duties for the and science resources available in the laboratory processes. I felt virtuous to National Institute of Mental Health and Washington, D.C. metro area. Fortu- be part of a company that was develop- the National Center for Complementary nately, my immediate love affair with ing therapeutic proteins to eventually and Alternative Medicine. Additionally, the sunny western city eased my sorrow

26 ASBMB Today August 2008 firstcareersecond insights words

and helped me look forward to a new mental consulting firm. The company, me to correspond with different scien- chapter in my career. SWCA Environmental Consultants, tists. From hydrologists and geologists It was a pleasant surprise to discover specializes in the management of to archaeologists and anthropologists, that Phoenix has a great deal to offer in natural resources, such as water, and professionals of every discipline work terms of jobs, but the city is not without cultural resources. They also assist together and offer a unique perspective its issues. As anyone who has spent time private and public sector clients in on what one can do with a passion for in the Valley of the Sun will tell you, the obtaining the necessary environmental science. impending water restrictions and possi- permits to complete their projects. My Am I where I once thought I would ble water shortage in the future is in the responsibilities include writing for and be, doing what I once thought I would back of many Phoenicians’ minds, if not editing internal and external corpo- be doing? No. on the tips of their tongues. I thought it rate newsletters; developing, editing, Am I content and fulfilled in my cur- might be an interesting challenge to take and disseminating messages from our rent career? Yes. a step back from health related roles and executive management team; leading I sort of like not knowing what the go to work for an organization whose all public relations efforts; and acting as future holds, and I figure that as long as objectives were more directly science a corporate representative at industry I’m doing something I enjoy–something oriented. conferences. I’ve been with SWCA for that, in my mind, makes a difference— I accepted a marketing communi- 2.5 years and I really enjoy my role, I’ll be happy. After all, isn’t that what cations writer position at an environ- particularly the aspects of it that allow life’s all about?

SAVE THE DATE!

Join the NIH Institutes, Centers, Offices, and their many partners engaged in research on minority health and health disparities to:

● Highlight the research progress of the NIH on health issues among racial/ethnic minority and medically underserved populations

● Increase awareness and understanding of disparities in health

● Showcase best-practice models in research, capacity-building, outreach, and integrated strategies to eliminate health disparities

● Identify strengths and gaps in health disparities research

● Network and dialogue with the nation’s leading experts on minority health and health disparities

REGISTER NOW ONLINE for this FREE Summit: www.ncmhd.nih.gov

Sponsored by: National Center on Minority Health and Health Disparities (NCMHD) biobits asbmb journal science

Another Role for Expand Your AMP-activated Nuclear Horizons Protein Kinase A cell’s nuclear membrane undergoes extensive remod- eling during the progression of the cell cycle. How this AMP-activated protein kinase (AMPK) was first identi- remodeling is coordinated remains a mystery, although it fied as a cellular energy sensor, but recently its role is likely coupled to phospholipid biosynthesis somehow. has been expanding into other biological processes. In a pair of related studies, joint researchers have identi- As discussed in this study, smooth muscle contrac- fied and characterized an unusual type of diacylglycerol tion might now be added kinase (DGK1) that helps regulate nuclear membrane to this growing list. The growth in yeast. In contrast to all other known diacylglyc- researchers have dem- erol kinases that rely on ATP, this enzyme uses CTP as onstrated that AMPK the phosphate donor to generate phosphatidic acid from phosphorylates myosin diacylglycerol (this substitution may explain why a DGK light chain kinase (MLCK) gene has not been identified in yeast until now). The in the calmodulin-binding researchers found that overexpressing DGK1 resulted domain (Ser815). Phos- in phosphatidic acid-enriched membranes and nuclear phorylation desensitizes envelope expansion, whereas mutations that abolished The aortic rings of α1-AMPK MLCK to calcium-trig- knock-out mice (open diacylglycerol kinase activity reduced phosphatidic gered calmodulin activa- box) display stronger acid levels and nuclear membrane growth. This nuclear contractions than wild-type tion and reduces its ability animals (black box) when expansion phenotype was similar to that of mutants to trigger myosin cross- stimulated by phenylephrine. defective in PAH1 (phosphatidic bridge formation and acid phosphatase), and muta- subsequent muscle contraction. In primary smooth tions in both DGK1 and PAH1 cell cultures, the addition of vasoconstrictors could restored normal phosphatidic activate AMPK in a calcium-dependent manner, and acid content and nuclear likewise mice lacking the smooth muscle isoform of membrane structure. This sug- AMPK experienced stronger contractions in the aortic gests a coordinated regulation ring. This study defines a potentially new signaling of diacylglycerol kinase and pathway controlling smooth muscle activity, in which Overexpressing the dia- phosphatidic acid phosphatase AMPK attenuates contractions by phosphorylating cylglycerol kinase in yeast activities in remodeling the MLCK. This attenuation might contribute to reduced leads to an expansion of the nuclear membrane. nuclear membrane. ATP turnover in the tonic phase of smooth muscle contraction. Characterization of the Yeast DGK1-encoded CTP-dependent Diacylglycerol Kinase AMP-activated Protein Kinase Phosphorylates Gil-Soo Han, Laura O’Hara, Symeon Siniossoglou, and and Desensitizes Smooth Muscle Myosin Light George M. Carman Chain Kinase J. Biol. Chem. 2008, 283, 20433–20442 Sandrine Horman, Nicole Morel, Didier Vertommen, Nusrat Hussain, An Unconventional Diacylglycerol Kinase Dietbert Neumann, Christophe Beauloye, that Regulates Phospholipid Synthesis Nicole El Najjar, Christelle Forcet, and Nuclear Membrane Growth Benoit Viollet, Michael P. Walsh, Gil-Soo Han, Laura O’Hara, George M. Louis Hue, and Mark H. Rider Carman, and Symeon Siniossoglou J. Biol. Chem. 2008, 283, 18505–18512 J. Biol. Chem. 2008, 283, 20443–20453

28 ASBMB Today August 2008 biobits asbmb journal science For more ASBMB journal highlights go to www.asbmb.org/Interactive.aspx

Good Fats, Bad Fats A 14-3-3 Framework Depending on their chain length and saturation level, The 14-3-3 proteins constitute a family of highly fatty acids (FAs) can exert varied biological effects on conserved and broadly expressed multifunctional the heart ranging from toxic to protective, although proteins that are involved in numerous important cel- the mechanisms mediating these observations are lular processes. unclear. In this study, the authors investigated these So far more than differential effects by subjecting adult rat cardiomyo- 300 cellular pro- cytes to 0.4 mM octanoate (8:0), palmitate (16:0), teins have been stearate (18:0), oleate (18:1), or linoleate (18:2) for 24 reported to h. They then used microarray analysis to compare interact with the gene expression patterns in response to the distinct 14-3-3 family, FAs, finding that saturated FAs influenced signifi- which contains cantly more genes (590-1,188) than unsaturated seven isoforms. ones (65-83). In this study, Cellular distribution of 14-3-3 isoforms in transformed human amnion (AMA) In general, car- the authors interphase cells. dioprotective examined how FAs like oleate these isoforms differ in expression, post-transla- increased tional modifications, and subcellular localization in expression of transformed human amnion (AMA) cells. Five of the genes promot- seven isoforms (b, e, s, t, and z) were present in AMA ing FA oxida- cells, and they were all expressed at analogous

Analysis of gene expression in adult rat tion to a greater levels throughout the cell cycle, suggesting that cell cardiomyocytes 24 h after challenge extent, whereas cycle-mediated events are not a major regulatory with octanoate, palmitate, stearate, oleate, or linoleate. cardiotoxic FAs mechanism of 14-3-3 proteins, at least in the AMA like palmitate cell system. There were noticeable differences in induced markers of endoplasmic reticulum and oxi- phosphorylation status and localization, however. dative stress. In addition, saturated and unsaturated The authors subsequently analyzed the isoforms in FAs had distinct time- and concentration-dependent over 20 established cell lines and tissue specimens, effects on similar target genes; for example, stearate- revealing that cellular context produces dramatic and palmitate-mediated ucp3 induction tended to be changes in expression and localization. The data transient, whereas oleate-mediated induction was presented in this study could prove to be a valuable sustained. These findings may provide new insights resource for other researchers working with 14-3-3 into why diets high in unsaturated FAs are beneficial, proteins. whereas diets rich in saturated FAs are not.

A Combined Proteome and Ultrastructural Bioinformatic Profiling of the Transcriptional Localization Analysis of 14-3-3 Proteins in Response of Adult Rat Cardiomyocytes to Transformed Human Amnion (AMA) Cells: Distinct Fatty Acids Definition of a Framework to Study Joseph B. Lockridge, Mary L. Sailors, Isoform-specific Differences David J. Durgan, Oluwaseun Egbejimi, José M. A. Moreira, Tao Shen, William J. Jeong, Molly S. Bray, Gita Ohlsson, Pavel Gromov, William C. Stanley, and Martin E. Young Irina Gromova, and Julio E. Celis J. Lipid Res. 2008 49, 1395-1408 Mol. Cell. Proteomics 2008 7, 1225-1240

August 2008 ASBMB Today 29 sciencefocus Karen Vasquez: Understanding Genome Structure and Stability BY NICK ZAGORSKI

he discovery of the DNA double officer in, coincidentally, the Houston love with triplex technology.” Thelix was truly a monumental area). “And when I wasn’t working, I Triplex technology arose from event that ushered in a new age of was exploring,” she says, noting that the observations that some single- molecular biology. However, we such adventures around her home stranded DNA pieces could bind to should note that Watson and Crick– nurtured a love of nature and biology. bases in the major groove of double- and Wilkins and Franklin–discovered She eventually became interested in stranded DNA through a pattern the A and B conformations of DNA, marine biology, and as the Midwest called Hoogsteen hydrogen bonding, but not the “only” conformations of didn’t really provide a suitable envi- thus creating a triple helix. In a prac- DNA. Since that 1953 breakthrough, ronment for such a pursuit, Vasquez tical sense (much like RNA interfer- researchers like Robert Wells and went south to the University of ence, which operates to inhibit gene Alexander Rich have discovered that Miami where she majored in marine activity by causing the destruction of DNA can come together in a variety science and biology, with a minor in gene-specific mRNA), forming a tri- of helical forms, including a left- chemistry for good measure. ple helix at targeted sites in the DNA handed Z-DNA helix and even triple- Near the end of her undergradu- can alter the expression of genes helical H-DNA. ate studies, however, Vasquez took of interest at the DNA level. “For The exact reasons DNA adopts a moment to reassess her goals. “I simply inhibiting gene expression, these nontraditional conformations definitely enjoyed marine science, RNA-based techniques are somewhat are still being worked out, and among but I was also interested in working better,” she says, “but if you want to those looking into DNA structure is in areas that could be directly applied directly modify the DNA, then triplex Karen Vasquez, Associate Professor in to human health, and marine biol- technology is the way to go.” the Department of Carcinogenesis at ogy didn’t seem like the optimal field It was such possible applications the University of Texas M.D. Ander- for that.” (Vasquez notes, however, that convinced Vasquez to stay at son Cancer Center. Since starting her that the marine world has contrib- Baylor College of Medicine for her lab in 2000, Vasquez has been study- uted greatly to medicine through the graduate work. “I saw the potential in ing the mechanisms of DNA damage numerous natural products uncov- applying triplex techniques for gene and repair from the perspective of ered from marine organisms.) therapy,” she says. In 1991, she joined how DNA secondary structures, par- Although Vasquez intended to go Baylor’s Biochemistry Department ticularly triple helix DNA, can influ- to graduate school, “my first order in the laboratory of John Wilson, ence these events. She hopes that she of business was saving some money who was studying DNA recombina- can exploit her findings to create new and paying off my loans.” So, after tion and its applications in disease, strategies for targeted therapies, such graduating from the University of particularly eye diseases. She began as inducing recombination events in Miami in 1987, she worked as a designing triplex-forming oligonucle- specific regions of DNA. research technician at the Nucleic otides (TFOs) and using them to Acid Research Institute in Costa induce DNA changes; for example, by Good Things Mesa, California, where she assisted adding a cross-linking agent to a TFO Come in Threes in projects developing nucleoside she could create site-specific damage Vasquez grew up in Michigan, sur- analogs as anticancer agents. In 1990 and force the repair of that region of rounded by 40 acres and six siblings, she moved to Houston and worked the DNA. including her identical twin sister for Michael Hogan at Baylor College Through her and Wilson’s work, Kim (who currently works as a police of Medicine, where, she says, “I fell in Vasquez found that TFOs could

30 ASBMB Today August 2008 sciencefocus

increase both the rates of sponta- bases can form backwards-winding what’s interesting about this is that neous mutations and homologous and strain-inducing Z-DNA, whereas there are no external factors produc- recombination in cells, making this 1 in every 50,000 bases might form ing DNA damage,” notes Vasquez. approach suitable to both insert and triple-helical H-DNA (also known “The DNA itself is the mutagen.” remove specific gene mutations. “This as “hinge DNA” because a piece of Vasquez believes that the H- and was pretty exciting because limita- duplex dislodges and wraps back- Z-DNA forms are often incorrectly tions of homologous recombination wards to form the triplex, while creat- recognized as “damaged DNA” by for gene therapeutic applications ing a small section of single-stranded repair enzymes; the enzymes might include its low frequency and its DNA as well). Such odds may look then perform an abortive repair, which tendency for random insertions,” she long, but when you consider that can lead to DNA strand breaks and says. “And TFOs might be able to human DNA has billions of base pairs translocation events. Vasquez found overcome both of those.” in each cell, it adds up. that such may be the case with the well After conducting a post-doc at Through her studies with H- and known oncogene c-MYC, which has Yale School of Medicine with Peter Z-DNA in mammalian cells, Vasquez an H-DNA “hot spot” in its promoter Glazer, applying triplex technology has found that like TFOs these confor- region. She adds that H-DNA creates to mutagenesis studies with mice, mations can create fragility, instabil- other problems as well, as it exposes Vasquez returned to Texas to start her ity, and mutations in the DNA. “But single-stranded regions of DNA that own lab at the University of Texas M.D. Anderson Cancer Center, Science- Park Research Division, H-DNA located away from the main campus in Hous- ton, near the small town ) 80 of Smithville. -4 70 The Science Park- 60 Research Division is 50 40 completely surrounded 30 by Buescher State Park in 20 the edge of the Texas Hill 10 Mutation0 Frequencies (X10 Country—“How many pCON pGG32 pAG32 pGA32 pcMyc pMycAG research facilities can provide a location like that?” she says. Double Strand Breaks Z-DNA A New Twist on DNA ) 140 -4 Whereas TFOs can 120 Deletion 100 induce chromosomal Recombination DNA changes by creat- 80 60 Translocation ing an unnatural DNA 40 structure, such unusual 20 helix formations also Mutation0 Frequency (x10

occur naturally, typically pUUY1 in regions rich in repeti- tive sequences. Estimates have suggested that Both H- and Z-DNA structures can increase the mutation rate of plasmid DNA in E. coli (gold) or COS-7 about 1 in every 5,000 cells (blue).

August 2008 ASBMB Today 31

Wang & Vasquez, PNAS , 2004 Wang et al, PNAS , 2006 science focus continued

are highly susceptible to radiation or chemical insult. Out of Focus: Considering the great risks they It Swims in the Family pose, a natural question that arises is why have these unusual structural Karen Vasquez had ambitions of becoming a marine biologist while grow- variants persisted from bacteria to ing up, and still likes to visit the beach when she can, so it may be no man? “That’s one of the active ques- surprise that her 5-year-old daughter Samantha currently also has career tions in this field,” says Vasquez, “but aspirations related to the marine field. However, Samantha is certainly tak- one possibility might be that these ing Karen’s goals one step further. “She wants to be a mermaid when she structures help spur evolution by grows up,” Vasquez says. It’s not the most feasible career goal, but the inducing double-stranded breaks and important thing, Vasquez notes, is that her daughter has the right motives. recombination, providing genetic “She wants to be a mermaid so she can help people, because in all the diversity. In addition, we’ve recently stories she hears that’s what mermaids do. found that H- and Z-DNA structures can both interfere with gene tran- scription, so they may also serve as and other upstream elements of genes tant aspect of Vasquez’s work has been yet another mechanism to regulate frequently contain H- and Z-DNA examining the molecular basis of gene expression.” susceptible sequences. In fact, Vasquez DNA damage recognition by the vari- Beneficial as they might be for a points out that some work suggests ous repair protein complexes, as well species, however, unstable DNA struc- that up to 90 percent of cancers can refining how DNA repair enzymes tures are still potentially disastrous for arise from defects in DNA repair or process unusual DNA structures and individuals; as in c-MYC, promoters recombination. Thus, another impor- site-specific DNA lesions.

Vasquez and her lab instructor (and former post-doc) Guliang Wang look at some yeast.

32 ASBMB Today August 2008 science focus continued

ily frustrations in work, but rather Family Ties Nick Zagorski, Ph.D., a graduate of a negative experience with the PI or Johns Hopkins and Cornell Universities, Instability may have some positive colleagues, and she strives to make is a science writer for ASBMB. He can be effects on DNA, but the same can’t be her own lab as positive as possible. reached at [email protected]. said for a research laboratory, an idea “The lab consists of research assis-

Vasquez has taken to heart. “One of tants, postdocs, students, and an References my biggest goals as a teacher and men- instructor (a non-tenure track faculty Belotserkovskii, B. P., De Silva, E., Tornaletti, S., Wang, G., Vasquez, K. M., and Hanawalt, P. C. (2007) A tor is to encourage students interested position), Dr. Guliang Wang, who Triplex-Forming Sequence from the Human C-MYC in science, especially women, to stick has performed much of the work on Promoter Interferes with DNA Transcription. J. Biol. Chem. 282, 32433-32441. with a career in science,” she says, non-B DNA structures in the labora- Wang, G., Christensen, L. A., and Vasquez, K. M. (2006) Z-DNA-forming Sequences Generate Large- adding that she doesn’t restrict a “sci- tory. Although they all have their scale Deletions in Mammalian Cells. Proc. Natl. ence career” to research. “It could be own independent projects, we all Acad. Sci. U.S.A. 103, 2677-2682. Wang, G., and Vasquez, K. M. (2004) Naturally through teaching, writing, advocacy, work together as well. I genuinely feel Occurring H-DNA-forming Sequences Are Mutagenic in Mammalian Cells. Proc. Natl. Acad. or many other things, but I try to help like my lab members are part of my Sci. U.S.A. 101, 13448-13453. young people interested in science find family, and that this sentiment helps Vasquez, K. M., Marburger, K., Intody, Z., and Wilson, J. H. (2001) Manipulating the Mammalian Genome some way to use that interest to benefit ensure success for my team because it by Homologous Recombination. Proc. Natl. Acad. Sci. U.S.A. 98, 8403-8410. science as a whole, because all these really fosters the sort of a cooperative Vasquez, K. M., Narayanan, L., and Glazer, P. M. different careers paths do intersect and setting that breeds happiness in life (2000) Specific Mutations Induced by Triplex- forming Oligonucleotides in Mice. Science 290, work together.” and innovation in science. It works 530-533. Vasquez acknowledges that a out well for me too because I never Vasquez, K. M., Wensel, T. G., Hogan, M. E., and Wilson, J. H. (1996) High-efficiency Triple Helix- major element that drives youngsters feel like I’m going to work; I’m just mediated Photo-cross-linking at a Targeted Site within a Selectable Mammalian Gene. Biochemistry away from science is not necessar- switching between families.” 35, 10712-10719.

National Academy of Sciences 2009 Awards in Biology Call for Nominations Nominations for these prestigious awards in Biology will be accepted through September 15, 2008. Visit www.nasonline.org/awards for details.

• Richard Lounsbery Award • Gilbert Morgan Smith Medal (biology and medicine—scientists age 45 (freshwater or marine algae) and younger) • John J. Carty Award for the Advancement • NAS Award in Molecular Biology of Science (2009 field—evolution) (scientists age 45 and younger) • NAS Award for Scientific Reviewing • Selman A. Waksman Award in Microbiology (2009 field—genetics)

National Academy of Sciences Awards www.nasonline.org | [email protected] | (202)334-1602 career opportunities

Visit www.asbmb.org for more listings and the latest career opportunities

Touro University Quillen College of Medicine— College of Medicine Department of Biochemistry Faculty Education Positions Assistant Professor in Biochemistry & Microbiology The Department of Biochemistry and Molecular Biology at the James Touro University College of Medicine is a newly created med- H. Quillen College of Medicine is seeking a full time research faculty ical school located in northern New Jersey, a few minutes member at the Assistant Professor level. This is a full-time research from NYC. We are seeking candidates to fill faculty educa- position in a non-tenure track. The position is for one year with a tion positions. These positions are responsible for develop- contract renewal option. Some salary support from grant funding ing, implementing and evaluating our medical education pro- is required. Research in the area of nutrient effects on cancer cell gram. Qualifications include a doctoral degree, a passion for proliferation is preferred. A PhD in biochemistry or a related field teaching and experience in a medical school environment. with two years of post-doctoral experience is required. For more information visit our Web site at http://touromed.edu Please submit a CV and two letters of reference to: Applicants should submit a letter of interest and current CV Dr. Scott Champney, Interim Chairman, Department of to: [email protected] Interest may be expressed Biochemistry and Molecular Biology, Quillen College of confidentially. Medicine. East Tennessee State University, Box 70581, Touro is an equal opportunity employer. Johnson City, TN 37614.

YET ANOTHER NEW OMEGA LABELED FLUORESCENT ® SPHINGOLIPID FROM AVANTI

Omega-NBD-Lyso SM Avanti Number 810203

Other Omega Labeled Fluorescent Sphingolipids now in stock: NBD Sphingosine, NBD Sphinganine, NBD 18:0 Ceramide, & NBD S-1-P

An extensive selection of Fatty Acid Labeled Fluorescent Sphingolipids also in stock Visit www.avantilipids.com for details

Phone 800-227-0651 (205-663-2494 International) or Email [email protected] for details of Avanti’s selection of lipids of unparalleled purity visit www.avantilipids.com

FROM RESEARCH TO CGMP PRODUCTION - AVANTI’S HERE FOR YOU

34 ASBMB Today August 2008

scientific meeting calendar

AUGUST 2008 SEPTEMBER 2008 OCTOBER 2008 Gordon Research 14th International 17th South East Lipid Conference—Membranes: Bioinformatics Workshop Research Conference Materials and Processes on Virus Evolution and OCTOBER 3–5, 2008 August 10–15, 2008 Molecular Epidemiology PINE MOUNTAIN, GA NEW LONDON, NH SEPTEMBER 1–5, 2008 www.selrc.org www.grc.org/programs.aspx?year=2008 CAPE TOWN, SOUTH AFRICA &program=membranes www.kuleuven.ac.be/aidslab/veme.htm Mitochondrial Biology in Cardiovascular Health HUPO 7th Annual Lupus Autoimmunity: and Diseases World Congress Mechanisms and Immune OCTOBER 6–7, 2008 AUGUST 16–21, 2008 Regulation BETHESDA, MD AMSTERDAM, THE NETHERLANDS SEPTEMBER 8–9, 2008 www.mitochondrial2008.com www.hupo2008.com LA JOLLA, CALIFORNIA E-mail: [email protected] E-mail: [email protected] www.biosymposia.org/content26853.html Tel.: 443-451-7254 Tel.: 514-398-5063 Workshop: Biology 2nd Congress of the Fifth International Conference of Signåaling in the International Society on Biology, Chemistry and Cardiovascular System of Nutrigenetics and Therapeutic Applications SEPTEMBER 11–14, 2008 Nutrigenomics of Nitric Oxide HYANNIS, MA OCTOBER 6–8, 2008 AUGUST 24–28, 2008 www.navbo.org/BSCS08Workshop.html GENEVA, SWITZERLAND BREGENZ, AUSTRIA www.symporg.com/conferences/2008/ www.register123.com/event/profile/web/ Symposium on Extracellular ISNN/index.html index.cfm?PKwebID=0x9794672ae and Membrane Proteases in Cell Signaling 9th International Congress Glutathione and Related SEPTEMBER 18–21, 2008 on Cell Biology, ICCB 2008 Thiols in Microorganisms AMES, IA OCTOBER 7–10, 2008 AUGUST 26–29, 2008 www.bb.iastate.edu/~gfst/homepg.html SEOUL, KOREA NANCY, FRANCE www.iccb2008.org/ Contacts: Jean-Pierre.jacquot@scbiol. uhp-nancy.fr, Pierre.Leroy@pharma. International Conference uhp-nancy.fr on Structural Genomics Glycobiology of https://matar.ciril.fr/THIOL/homephar.php SEPTEMBER 20–24, 2008 Human Disorders OXFORD, UK OCTOBER 9-13, 2008 www.spine2.eu/ISGO 17th Meeting of Methods in ATLANTA, GA Protein Structure Analysis Organizer: Richard D. Cummings, Keystone Symposium— Emory University AUGUST 26–29, 2008 www.asbmb.org/meetings.aspx SAPPORO, JAPAN Metabolism and www.e-convention.org/mpsa2008 Cardiovascular Risk E-mail: mpsa2008sapporo@e- SEPTEMBER 23–28, 2008 BRECKENRIDGE, CO Translating Science into convention.org Health: Cytokines in Cancer Tel.: 81-11-272-5880 www.keystonesymposia.org/Meetings/ ViewMeetings.cfm?MeetingID=999 and Infectious Diseases OCTOBER 12–16, 2008 49th International Conference World Congress on the MONTREAL, Quebec on the Bioscience of Lipids www.cytokines2008.org AUGUST 26–30, 2008 Insulin Resistance Syndrome MAASTRICHT, THE NETHERLANDS SEPTEMBER 25–27, 2008 www.unimaas.nl/congresbureau/icbl2008/ LOS ANGELES, CA Transcriptional www.insulinresistance.us Regulation by Chromatin 30th European Peptide and RNA Polymerase II Society Symposium 13th International Congress OCTOBER 16–20, 2008 AUGUST 31–SEPTEMBER 5, 2008 on Hormonal Steroids and GRANLIBAKKEN, LAKE TAHOE Organizer: Ali Shilatifard, Stowers HELSINKI, FINLAND Hormones & Cancer Institute for Medical Research www.30eps.fi/ SEPTEMBER 27–30, 2008 Plenary Lecturer: Robert G. Roeder, E-mail: [email protected] QUEBEC CITY, Quebec The Rockefeller University Tel.: 358-(0)9-5607500 www.ichshc2008.com/ www.asbmb.org/meetings.aspx

36 ASBMB Today August 2008 scientific meeting calendar

Cellular Lipid Transport- DECEMBER 2008 2nd International Conference Connecting Fundamental on Advanced Technologies Membrane Assembly The Annual Meeting and Treatments for Diabetes Processes to Human of the American Society (ATTD) Disease for Matrix Biology (ASMB) FEBRUARY 25–28, 2009 DECEMBER 7–11, 2008 ATHENS, GREECE OCTOBER 22–26, 2008 www.2.kenes.com/attd/Pages/home.aspx CANMORE, ALBERTA, CANADA SAN DIEGO, CA Organizers: Dennis R. Voelker, www.asmb.net/ National Jewish Medical Research APRIL 2009 Center; Jean Vance, University The 48th American Society for of Alberta, Edmonton; and Todd Cell Biology Annual Meeting Graham, Vanderbilt University 3rd International Congress DECEMBER 13–17, 2008 www.asbmb.org/meetings.aspx on Prediabetes and the SAN FRANCISCO, CA Metabolic Syndrome— www.ascb.org/meetings/ Epidemiology, Management, Post Translational and Prevention of Diabetes Modifications: Detection and Cardiovascular Disease & Physiological Evaluation JaNUARY 2009 APRIL 1–4, 2009 OCTOBER 23–26, 2008 Keystone Symposium– NICE, FRANCE GRANLIBAKKEN, LAKE TAHOE Obesity: Novel Aspects of the www.kenes.com/prediabetes Organizers: Katalin F. Medzihradszky Regulation of Body Weight and Ralph A. Bradshaw, UCSF JANUARY 20–25, 2009 www.asbmb.org/meetings.aspx ASBMB Annual Meeting BANFF, ALBERTA, CANADA APRIL 18–22, 2009 www.keystonesymposia.org/Meetings/ NEW ORLEANS, LA ViewMeetings.cfm?MeetingID=997 www.asbmb.org/meetings 48th ICAA/IDSA 46th Annual Meeting October 25–28 February 2009 Washington, DC MAY 2009 www.icaacidsa2008.org Gordon Research Conference– Plant Lipids: Structure, 57th ASMS Conference on Mass Spectrometry Protein Design Metabolism, & Function and Evolution FEBRUARY 1–6, 2009 MAY 31–JUNE 4, 2009 GALVESTON, TX PHILADELPHIA, PA for Biocatalysis www.grc.org/programs.aspx?year=2009&pr www.asms.org OCTOBER 25–30, 2008 ogram=plantlipid E-mail: [email protected] SANT FELIU DE GUIXOLS, SPAIN Tel.: 505-989-4517 www.esf.org/index.php?id=4569 The 14th Annual Proteomics Symposium NOVEMBER 2008 FEBRUARY 6–8, 2009 JUNE 2009 LORNE, AUSTRALIA www.australasianproteomics.org VIII European Symposium 2nd Latin American Protein of the Protein Society Society Meeting JUNE 7–11, 2009 NOVEMBER 4–8, 2008 US HUPO 5th Annual ZURICH, SWITZERLAND ACAPULCO, GRO. MEXICO Conference Organizer: Andreas Plückthun www.laproteinsociety.org FEBRUARY 22–25, 2009 (University of Zurich) SAN DIEGO, CA www.proteinsociety.org 2008 Annual Meeting of www.ushupo.org the Society for Glycobiology E-mail: [email protected] 3rd EuPA Meeting— NOVEMBER 12–15, 2008 Tel.: 505-989-4876 Clinical Proteomics FORT WORTH, TX June 14–17, 2009 www.glycobiology.org Keystone Symposium– Stockholm Sweden Complications of www.lakemedelsakademin.se/templates/ Oils + Fats 2008 Diabetes and Obesity LMAstandard.aspx?id=2529 NOVEMBER 18–20, 2008 FEBRUARY 24–MARCH 1, 2009 MUNICH, GERMANY VANCOUVER, BRITISH COLUMBIA www.oils-and-fats.com www.keystonesymposia.org/Meetings/ APRIL 2010 E-mail: [email protected] ViewMeetings.cfm?MeetingID=998 ASBMB Annual Meeting APRIL 24–28, 2010 ANAHEIM, CA www.asbmb.org/meetings 2008 ASBMB Special Symposia Series

Glycobiology of Human Disorders October 9-13, 2008 Emory University Conference Center, Atlanta, GA Organizer: Richard D. Cummings, Emory University Abstract Submission Deadline: September 5, 2008

Transcriptional Regulation by Chromatin and RNA Polymerase II October 16-20, 2008 Granlibakken, Lake Tahoe Organizer: Ali Shilatifard, Stowers Institute for Medical Research Plenary Lecturer: Robert G. Roeder, The Rockefeller University Abstract Submission Deadline: September 5, 2008 Cellular Lipid Transport: Connecting Fundamental Membrane Assembly Processes to Human Disease October 22-26, 2008 Radisson Hotel & Conference Center, Canmore, Alberta, Canada Organizers: Dennis R. Voelker, National Jewish Medical Research Center, Jean Vance, University of Alberta, Edmonton, and Todd Graham, Vanderbilt University Plenary Lecturer: Robert Molday, University of British Columbia Abstract Submission Deadline: September 5, 2008

Post Translational Modifications: Detection and Physiological Evaluation October 23-26, 2008 Granlibakken, Lake Tahoe Organizers: Katalin F. Medzihradszky, and Ralph A. Bradshaw, UCSF Plenary Lecturer: M. Mann, Max Planck Institute of Biochemistry, Martinsried Abstract Submission Deadline: September 15, 2008

To Register Visit Us Online http://www.asbmb.org/meetings.aspx