HHMI BULLETIN N OV. ’09 VOL.22 t NO.04 4000 Jones Bridge Road r Chevy Chase, Maryland 20815-6789 Hu Howard www.hhmi.org HHMI BULLETIN g hes Medical Institute Going Tubular Your spinal cord, the bundle of nerves that carries messages between your brain and the rest of your body, is housed in a hollow tube that started out flat as a pancake. During embryonic development, the flat sheet of cells folds in on itself r and closes up by the fourth week after conception. The same cellular orchestra- tion happens in most vertebrate embryos, including the frog embryo shown here. www.hhmi.or Movement of these cells involves contraction of filaments called actin (green). On the right, they’ve contracted and begun forming a tube, so the green is more concentrated. When genetic control of the rolling process is perturbed, as it has been on the left side of this embryo, actin does not contract and the sheet stays g flat. Failure to form the so-called “neural tube” lies at the root of several human birth defects, including spina bifida. Read about research on neural tube forma- tion and more in “The Most Vulnerable Patients” (page 12). IN THIS ISSUE Kerry Ressler Fights Fear Membrane Awakening Training TAs TO FULL vol. vol. POTENTIAL 22 / no. / no. Chanjae Lee / Wallingford lab Chanjae Lee / Wallingford Researchers aim to protect babies from 04 the complications of prematurity. OBSERVATIONS 24 Like lips around a straw, the membranes around the channels that control water flow into and out of a cell must form a tight seal. Using electron crystallography, researchers produced this image of the water channel called aquaporin-0. The amino acid residues that make up the protein (blue) are arranged in a unique configuration that allows water molecules (red) to pass through. Hydrophobic lipids (yellow) form snug belts around each protein, creating moisture-repellent barriers ©2009 that help channel the water. Nature VISUALIZE THIS You could say membrane channels really caught Rod MacKinnon’s eye. was clear. The conservation of the signature sequence amino acids Trained as a physician, MacKinnon abandoned medicine for a life in in K+ channels throughout the tree of life, from bacteria to higher science after studying, during a medical residency, how potassium eukaryotic cells, implied that nature had settled upon a very special channels enable the heart to contract and relax. A desire to see those solution to achieve rapid, selective K+ conduction across the cell channels—to see how they physically do their job—pushed him into membrane. For me, this realization provided inspiration to want to structural biology, a field of research that proved providential. In 1998, directly visualize a K+ channel and its selectivity filter. I began to he produced the first high-resolution three-dimensional image of a study crystallography, and although I had no idea how I would obtain potassium channel, a feat that garnered MacKinnon the 2003 Nobel funding for this endeavor, I have always believed that if you really Prize in Chemistry. want to do something then you will find a way. Ion selectivity is critical to the survival of a cell. How does nature accomplish high conduction rates and high selectivity at the same From Roderick MacKinnon’s Nobel Prize Lecture. ©The Nobel Foundation time? The answer to this question would require knowing the atomic 2003. Reprinted with permission of the Nobel Foundation. structure formed by the signature sequence amino acids, that much Mike Perry Courtesy of Tamir Gonen and Thomas Walz. Reprinted with permission from Macmillan Publishers Ltd: Gonen and Thomas Walz. Courtesy of Tamir november ’o9 vol. 22 · no. o4 18 12 web only content Visit the online Bulletin to see an audio slideshow of new teaching assistant Joe DePalma as he goes into his first day as a chemistry lab instructor at the University of Delaware and an audio slideshow of Catherine Drennan’s MIT training class for TAs on student diversity. Listen to Charles Sawyers give his view on the value of translational research and watch him move through a typical work day at Memorial Sloan-Kettering Cancer Center. Read about how a model bacterium is showing sci- entists how pathogens go from harmless to deadly: Pascale Cossart is building a library of knowledge on Listeria, and her methods are informing studies of viral and parasitic infections as well. All of this and more at www.hhmi.org/bulletin/nov2009. 30 24 Features Departments COVER STORY PRESIDENT’S LETTER LAB BOOK THE MOST VULNERABLE PATIENTS 03 Season of Change 40 Removing Radiation Roadblock 12 Problems during pregnancy burden 41 Starving for GABA CENTRIFUGE too many newborns with lifelong 42 Blue Baby Blues disabilities. Researchers are 04 From the Outside Looking In finding clues to a safer nine months, 05 Where Past Meets Future ASK A SCIENTIST and a brighter future. 06 Leapin’ Lizards 43 Does the anatomy of freshwater and saltwater fish differ? UPFRONT TAMING FEAR, RISING CALM 08 TOOLBOX 18 A social conscience rooted in the Piecing Together Rotavirus’s Deep South moves Kerry Ressler, Unique Approach 44 Freeze Frame 10 Seeing Spots a psychiatrist and neuroscientist, NOTA BENE to try to ease the consequences of PERSPECTIVES AND OPINIONS 46 News of recent awards and inner city trauma. 34 Terrence Sejnowski other notable achievements 36 MEMBRANE AWAKENING Q&A: What grade in school was OBSERVATIONS 24 your most formative and why? Researchers are taking a more Visualize This holistic look at cell membranes and CHRONICLE the proteins embedded in them— SCIENCE EDUCATION and the surprises keep coming. 38 Rummaging for Science 39 2009 Holiday Lectures on Science: ENHANCING TA PERFORMANCE Exploring Biodiversity 30 Instead of letting teaching assistants sink or swim, risking their failure and the ire of the undergrads, some schools are prescribing a class in how to teach before they get in front of a class. VISIT THE BULLETIN ONLINE FOR ADDITIONAL CONTENT AND ADDED FEATURES: www.hhmi.org/bulletin COVER IMAGE: JASON HOLLEY contributors Change is in the air. For what seems like a while camps. On our website you’ll find two audio now, we’ve been experiencing adjustments in slideshows—one gives you a glimpse into an the way we live, work, and play—some easier MIT training course on diversity, and in the to embrace than others. Here at the Bulletin, other you get to tag along on a University of we’re going through some changes, too. All for Delaware TA’s first day as lab instructor. the better, I think, and I hope you’ll agree. Other stories are moving online as well, With this issue, we’ve gone a little shorter, including one of our usual trio of Upfront arti- by eight pages. We haven’t lost the content cles. With this issue, you can go online to read you are accustomed to seeing, it’s just moved about the recent discoveries of HHMI interna- online—and expanded, in some cases. It made tional research scholar Pascale Cossart on the sense to trim Bulletin costs by slightly reduc- biology of Listeria infection—and watch a short ing the print version, while offering existing video of how the bacteria infect a cell. content and then some on the Web. In coming editions of the Bulletin, we intend By visiting the online version of this issue, for to expand our Web extras, in the form of addi- example, you’ll find a multimedia perspective tional stories and interactive multimedia. We piece by HHMI investigator Charles Sawyers. hope you’ll continue to enjoy our print maga- In this short audio slideshow, you can listen to zine, and visit the online version to learn even Sawyers give his view on the value of transla- more about HHMI’s research and science edu- tional research and watch him move through a cation efforts. Our goal, as always, is to pro- typical work day at Memorial Sloan-Kettering duce engaging content that both informs and Cancer Center. inspires. Drop me a line and let me know how One of our feature articles is shorter, with we’re doing. some added extras on the Web. That feature presents the efforts by some universities to give novice teaching assistants, or TAs, a welcome boost in the form of training courses and boot HHMI TRUSTEES HHMI OFFICERS & SENIOR ADVISORS James A. Baker, III, Esq. Robert Tjian, Ph.D. / President Senior Partner / Baker Botts L.L.P. Craig A. Alexander / V.P. & General Counsel Ambassador Charlene Barshefsky Peter J. Bruns, Ph.D. / V.P. for Grants & Special Programs Senior International Partner Jack E. Dixon, Ph.D. / V.P. & Chief Scientific Officer WilmerHale Joan S. Leonard, Esq. / Senior Counsel to the President Joseph L. Goldstein, M.D. Avice A. Meehan / V.P. for Communications & Public Affairs Regental Professor & Chairman, Department of Molecular Genetics Edward J. Palmerino / V.P. for Finance & Treasurer University of Texas Southwestern Medical Center at Dallas Gerald M. Rubin, Ph.D. / V.P. & Director, Janelia Farm Research Campus Hanna H. Gray, Ph.D., Chairman Landis Zimmerman / V.P. & Chief Investment Officer President Emeritus & Harry Pratt Judson Distinguished Service Professor of History HHMI BULLETIN STAFF The University of Chicago Mary Beth Gardiner / Editor Cori Vanchieri Garnett L. Keith / Story Editor Chairman / SeaBridge Investment Advisors, L.L.C. Jim Keeley / Science Editor Former Vice Chairman & Chief Investment Officer Andrea Widener / Science Education Editor The Prudential Insurance Company of America Patricia Foster / Associate Director of Communications Paul Nurse, F.R.S. for Web & Special Projects President / The Rockefeller University Sarah C.P. Williams / Assistant Editor Alison F. Richard, Ph.D. Maya Pines / Contributing Editor Vice-Chancellor ADDITIONAL CONTRIBUTORS The University of Cambridge Cay Butler, Michelle Cissell, Clayton S.