Sugar Coated Sugar Has Become Notorious, with Countless Claims of Its Ill Effects on Health

HHMI BULLETIN N OV . ’11 VOL.24 • NO.04 • 4000 Jones Bridge Road Chevy Chase, Maryland 20815-6789 Hughes Medical Institute Howard www.hhmi.org Address Service Requested Sugar Coated Sugar has become notorious, with countless claims of its ill effects on health. But not all sugars are bad for you. Consider fucose, an essential sugar the body needs. Without it, neurons can’t communicate, kidneys can’t filter blood, and skin can’t stay hydrated. Chemical biologist Carolyn • Bertozzi and her group are trying to learn more about the role of fucose in www.hhmi.org development. To do this, they injected modified versions of fucose into live, single-celled zebrafish embryos. As the embryos developed, the altered fucose molecules were incorporated into the sugars that coat cell surfaces. Using a simple chemical reaction, the team attached a labeled probe molecule to the altered fucose so they could visualize its location in the developing embryo. In this image of a 19-hour-old zebrafish embryo, labeled fucose (red) glows in the peripheral cells. Just one of many ways chemistry is helping answer biological questions (see “Living Chemistry,” page 12). YEAR OF CHEMISTRY Chemists fascinated by the complexity of biology are solving problems in neuroscience, immunology, and cell signaling. v ol. 24 / no. no. / Karen Dehnert and Scott Laughlin / Bertozzi lab In This Issue: Traveling Microscope / Lemur vs Mouse / Spotlight on Science Teacher Training 04 ObservatiOns ThE GIvInG TREE The history of science overflows with captivating stories of break- Johann Kraut in 1869 and Hermann Kolbe in 1874, but then, unfortunately, throughs that led to innovative disease treatments. Chemical biologist this molecule languished, with little interest in its medicinal properties. Brent Stockwell chose his favorites—including the story of aspirin— in a new book on the science behind drug discoveries. In the telling, At the end of the nineteenth century, many researchers began to pursue 24 Stockwell reveals how curiosity, persistence, and scientific know-how medicines that could reduce fever, with the rationale that fever could Catching chromosomes in the act, this still frame of a dividing human combine in sometimes powerful and far-reaching ways. be damaging to the body. These so-called anti-pyretics (fever-reducing cancer cell, an osteosarcoma cell, comes from video recorded by Bessel molecules) were aggressively sought. The nascent pharmaceutical beam plane illumination microscopy. Developed by Eric Betzig and In many cases, extraction and synthesis methods have been combined company Bayer introduced acetylsalicylic acid as an anti-pyretic in 1899, his team at Janelia Farm, the microscope directs a narrow pencil of to make derivatives of molecules found in nature. An example of this type coining the name “aspirin.” This fever-reducing drug quickly became light to illuminate a single plane within a specimen and then repeats, of combined approach is the discovery of fever-reducing drugs. popular around the world. It was the first of the non-steroidal anti- plane by plane, until the entire volume is imaged. Combining 3-D inflammatory drugs (NSAIDs) used. Subsequently, other NSAIDs were spatial resolution with high speed and minimal light-induced damage, An active component of Willow tree extract is salicin. Raffaele Piria, an introduced, such as ibuprofen (now sold as Advil). Such drugs represent a the approach is particularly suited for imaging activity within living Italian chemist, prepared salicylic acid from salicin, which was advanta- huge class of beneficial medicines that are widely used around the globe. cells—something that biologists have been eager to do. geous because salicylic acid was easier to modify into other molecules compared to salicin. Salicylic acid, however, caused gut toxicity, and so was Excerpt from The Quest for the Cure: The Science and Stories Behind of limited value. Charles Frédéric Gerhardt, a French chemist, then synthe- the Next Generation of Medicines, by Brent R. Stockwell, © 2011 Brent R. sized a key derivative named acetylsalicylic acid in 1853. Refined methods Stockwell, published by Columbia University Press. Used by permission Betzig lab Emily Roberston for synthesizing acetylsalicylic acid were developed by two chemists, of the author and Columbia University Press. november ’11 vol. 24 · no. o4 12 18 Web Only Content Hear Eric Betzig talk about taking his new microscope to Woods Hole and see how it dazzled summer students and faculty. Learn how Irv Epstein brings chemistry alive for students in the classroom. Travel with Mark Krasnow to the rainforests of Madagascar to spy the mouse lemur in its native habitat. Join us at www.hhmi.org/bulletin/nov2011. 24 30 Features Departments cover story presiDent’s L etter institUte neWs Living chemistry 03 Intellectual Ferment 40 Experiment Seeks to Create 1 2 As engineers of the molecular centriFUge Interdisciplinary Curricula world, chemists are making their 40 HHMI Offers International 04 Game Changer mark in biology. Student Research Fellowships 05 Stirring Debate 41 Getting Back to the Bench caLLing a LL teachers 06 The Peripatetic Postdoc 1 8 Everyone agrees that the U.S. needs Lab book UpFront to train a new generation of inspiring 42 Unlocking the Interferon Puzzle 08 Creating Internal Maps science teachers. But how? 43 When Membranes Merge 1 0 Helping Preemies have microscope, Wi LL traveL 44 Bacterial-Viral Warfare perspectives anD opinions 24 Biology students and faculty a sk a scientist 34 Changed Expectations immersed in science courses at 45 How fast would an object have to 36 Q&A—What was your first cool Woods Hole get their hands on a chemistry experiment—one that move to be invisible to the naked eye? remarkably powerful imaging tool turned you on to research before nota bene developed at Janelia Farm. you were a bona fide scientist? 46 News of recent awards and other s tar search chronicLe notable achievements 30 Could the grey mouse lemur be the science eDUcation OBSERVATIONS next best model for human disease? 38 Room to Grow—and Learn The Giving Tree VISIT THE BULLETIN ONLINE FOR ADDITIONAL CONTENT AND ADDED FEATURES: www.hhmi.org/bulletin COVER IMAGE: MARIO HUGO editor’s letter teacher, Mrs. otwell—a woman with sharp we spotlight the need in this country for intelligence and charismatic delivery who more, and better, science teachers in our taught me the “bus seat rule,” to illustrate schools. In other articles, we pay hom- the orderly manner in which electrons fill age to the increasingly powerful role that atomic shells, and the meaning of a quark. chemists play in biological discovery— I wasn’t the only one in my family chemists who no doubt got their start touched by Mrs. otwell’s teaching magic. being fascinated by the fundamentals with one of my older brothers majored in chem- teachers like Mrs. Barnes and Mrs. otwell. istry in college, and my sister, who as a Star Don’t miss the multimedia slideshows Student in high school named Mrs. otwell and other extras in this issue, which can In the fifth grade, I won a blue ribbon at her Star Teacher, is now an academic be found online and in our iPad app. The my school’s science fair. Truth be told, it researcher studying bone genetics. digital versions of the Bulletin are proving wasn’t much of a project—I grew a “pop- Who’s to say what might have been had a great way to expand on the stories we corn plant” from an unpopped corn kernel. the early spark that Mrs. Barnes lit been offer in print—for example, find new details But my teacher, Mrs. Barnes, saw some- fanned into a flame during my later school of Matt Warman’s bone research, first cov- thing there. years? After switching my college major ered in the May 2011 issue. The magazine’s I treasured that ribbon, and it could from English to biology, I eventually arrived stories continue to have lives long after be that Mrs. Barnes’s vote of confidence at a career in science, first in the research they land in your mailbox, and we’ll use our launched me toward my graduate degree lab and now as a science writer and edi- website to update them as we go. in biology. Sadly, though, the rest of my tor. It was the right path for me, though I elementary, middle-, and high school years sometimes imagine how things might have were almost bereft of science, with few been different. good science teachers. The one excep- Clearly, those formative K-12 school tion was my eleventh grade chemistry years are critical. In this issue of the Bullet in, HHMI TRUSTEES HHMI OFFICERS James A. Baker, III, Esq . Robert Tjian, Ph.D. / President Senior Partner / Baker Botts LLP Cheryl A. Moore / Executive V.P. & Chief Operating Officer Craig A. Alexander Ambassador Charlene Barshefsky / V.P. & General Counsel Senior International Partner Sean B. Carroll, Ph.D . / V.P. for Science Education WilmerHale Jack E. Dixon, Ph.D . / V.P. & Chief Scientific Officer Joseph L. Goldstein, M.D . Mohamoud Jibrell / V.P. for Information Technology Regental Professor & Chairman / Department of Molecular Genetics Nitin Kotak / V.P. & Chief Financial Officer University of Texas Southwestern Medical Center at Dallas Avice A. Meehan / V.P. for Communications and Public Affairs Hanna H. Gray, Ph.D. Gerald M. Rubin, Ph.D . / V.P. & Executive Director, President Emeritus & Harry Pratt Judson Janelia Farm Research Campus Distinguished Service Professor of History Landis Zimmerman / V.P. & Chief Investment Officer The University of Chicago Garnett L. Keith HHMI BULLETIN STAFF Chairman / SeaBridge Investment Advisors, LLC Mary Beth Gardiner / Editor Former Vice Chairman & Chief Investment Officer Cori Vanchieri / Story Editor The Prudential Insurance Company of America Jim Keeley / Science Editor Fred R.

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