hhmi bulletin • howard hughes medical institute • www.hhmi.org • institute medical hughes howard • bulletin hhmi Fall ’13 Vol. 26 No. 3 4000 Jones Bridge Road Chevy Chase, Maryland 20815-6789 www.hhmi.org Address Service Requested Competitive Streak in this issue Teeming bacteria of all stripes make their home in the gut. Like On Cancer’s Trail siblings sharing a bedroom, the microbes can get a little competitive 2013 Investigators for nutrients and other molecules they need to grow. Katrina Xavier Forest Fires and her research team aim to identify traits that neither help nor hurt Escherichia coli bacteria grown in pure cultures but are beneficial when the bacteria have to compete with other species in a complex environment like the gastrointestinal tract. The macro-colony seen here is a mixture of two mutant E. coli strains that differentially express fluorescently labeled proteins (yellow and blue) when grown in competition on an agar plate. The two markers indicate the fitness of each strain as they compete. To learn more about the team’s work, see “Microbial Social Network,” page 12. The Din Within Microbial messaging in the gut keeps the body humming vol. 26 / no. 3 no. / 26 vol. Ozhan Ozkaya / Xavier Lab Xavier / Ozkaya Ozhan HHMI Bulletin / Fall 2013 For more information: See the feature profile Observations of Bert Vogelstein, “Driven,” on page 18. Knowing the heterogeneity of every cancer, one might naively have presumed that every patient’s cancer possessed its own sequence of gene mutations and its 24 unique set of mutated genes. But Vogelstein Interstellar dust cloud? found a strikingly consistent pattern in his Cancer geneticist already knew two Distant galaxy? Not quite, colon cancer samples: across many samples answers to this question. First, proto-oncogenes and many patients, the transitions in the needed to be activated through mutations, though it is a vista into the stages of cancer were paralleled by the same and mutations are rare events. Second, tumor brain. This is a collection transitions in genetic changes. Cancer cells suppressor genes need to be inactivated, of neurons, labeled in did not activate or inactivate genes at random. but typically two copies exist of each tumor a unique way to track Instead, the shift from a premalignant suppressor gene, and thus two independent voltage changes that help state to an invasive cancer could precisely mutations are needed to inactivate a tumor be correlated with the activation and suppressor, an even rarer event. Vogelstein the cells communicate. The Road to inactivation of genes in a strict and provided the third answer. Activating or Adam Cohen developed the stereotypical sequence.... inactivating any single gene, he postulated, technique using microbial Cancer’s Abyss This was a relief. In the decade between produced only the first steps toward rhodopsins—bacterial In Siddhartha Mukherjee’s bestseller 1980 and 1990, proto-oncogenes and tumor carcinogenesis. Cancer’s march was long and proteins that convert on the history of cancer, HHMI Investigator suppressor genes had been discovered in slow and proceeded through many mutations such astonishing numbers in the human in many genes over many iterations. In genetic sunlight into electricity. Bert Vogelstein at the Johns Hopkins genome—at last count, about one hundred terms, our cells were not sitting on the edge of When the rhodopsins Medical School plays the role of mapmaker. such genes—that their abundance raised the abyss of cancer. They were dragged toward are run in reverse, they Through his research, he begins to make a disturbing question: if the genome was that abyss in graded, discrete steps. so densely littered with such intemperate fluoresce each time a pulse sense of the mess of genetic changes that lead From THE EMPEROR OF ALL MALADIES: A genes—genes waiting to push a cell toward of electricity races through to a handful of cancers and maps out several Biography of Cancer by Siddhartha Mukherjee. cancer as if at the flick of a switch—then why long pathways that have become targets for Copyright © 2010 by Siddhartha Mukherjee, a neuron, producing an was the human body not exploding with MD. Reprinted by permission of Scribner, a otherworldly glow. Cohen Adam and Hochbaum Daniel Pemberton Simon early detection and new therapies. cancer every minute? Division of Simon & Schuster. credit Photo ContentsFall ’13 Vol. 26 No. 03 Departments president’s letter 03 Investing in the Basics centrifuge 04 Camp Normal 05 Perennial Treasure bench report 06 Intoxicating Research 08 The Guide on the Side 10 Time to Sprout perspectives & opinions 30 Hypothesis: Unknown 32 Q&A – Tell us about an observation that sent your research in an unexpected direction. chronicle 34 Science Education Partners for the Environment 36 Toolbox Now You See It 38 Lab Book Community Building Dialing Back a Disease A Helpful Hormone observations The Road to Cancer’s Abyss Features 12 Microbial Social Network Decoding bacterial chatter Microbial Social Network, page 12 may clarify our relationship to their vast communities. 18 Driven See students get a hands-on— www.hhmi.org/bulletin Bert Vogelstein is on a mission and feet-in—experience that Web-Only Cover image: to change the outlook for teaches them about the biology Mattias Adolfsson people with cancer. Content of a stream. Join several new HHMI Watch male fruit fl ies turn This paper is certifi ed by SmartWood 24 Explorers investigators as they discuss to alcohol after their sexual for FSC standards, which promote After an intense competition, the draw of science, the role advances are rejected. environmentally appropriate, socially 27 scientists had the right of creativity in research, and benefi cial, and economically viable Learn how HHMI fi nds creative learning on the job. management of the world’s forests. stuff to be named HHMI scientists with the potential investigators. Where will their Take a journey through a to make groundbreaking curiosity take them? transparent mouse brain. discoveries. 2 Fall 2013 / HHMI Bulletin Contributors HHMI TRUSTEES Kurt L. Schmoke, Esq., Chairman Vice President & General Counsel / Howard University James A. Baker, III, Esq. Senior Partner / Baker Botts LLP Ambassador Charlene Barshefsky Senior International Partner / WilmerHale Susan Desmond-Hellmann, MD, MPH Chancellor / University of California, San Francisco Joseph L. Goldstein, MD Regental Professor & Chairman / Department of Molecular Genetics University of Texas Southwestern Medical Center Garnett L. Keith Chairman / SeaBridge Investment Advisors, LLC Former Vice Chairman & Chief Investment Offi cer The Prudential Insurance Company of America Fred R. Lummis Chairman & CEO / Platform Partners LLC Sir Paul Nurse President / The Royal Society Dame Alison F. Richard, PhD Professor / Yale University Mattias Adolfsson (cover and Clayton S. Rose, PhD “Microbial Social Network,” Professor of Management Practice page 12) is a freelance illustrator Harvard University Anne M. Tatlock operating from Sigtuna, outside Scottish-born photographer Director, Retired Chairman, & CEO Stockholm, Sweden. In addition Graham MacIndoe (“Driven,” Fiduciary Trust Company International to sketching bacteria and viruses, page 18) lives and works out HHMI OFFICERS he makes other commissioned of New York City. He shoots Robert Tjian, PhD / President works but always fi nds time for for editorial, corporate, and Cheryl A. Moore / Executive VP & moderate walks in the forest and advertising clients, including Chief Operating Offi cer Kathryn S. Brown / Head of Communications personal drawings. The New York Times Magazine, Sean B. Carroll, PhD / VP for Science Education The Guardian Magazine, and Heidi E. Henning / VP & General Counsel W magazine, among others. Mohamoud Jibrell / VP for Information Technology Current personal projects Nitin Kotak / VP & Chief Financial Offi cer include one about addiction Erin O’Shea, PhD / VP & Chief Scientifi c Offi cer and recovery and another Gerald M. Rubin, PhD / VP & on immigration detention in Executive Director, Janelia Farm Research Campus the United States. Kathy A. Wyszynski / VP for Human Resources Landis Zimmerman / VP & Chief Investment Offi cer Sarah C.P. Williams HHMI BULLETIN STAFF Mary Beth Gardiner / Editor (“Microbial Social Network,” Cori Vanchieri / Story Editor page 12) can’t seem to cut her ties Jim Keeley / Science Editor to HHMI. She’s been associated Nicole Kresge / Assistant Editor with the Institute fi rst as a ADDITIONAL CONTRIBUTORS budding scientist—through Cay Butler, Michelle Cissell, Mark Farrell, an undergraduate research Heather McDonald Pentagram Design / Design fellowship a decade ago—then Al Murphy (“Intoxicating Allied Printing / Printing & Binding as a staff member of the HHMI Research,” page 6) is a British Bulletin, and now as a freelance illustrator who loves to draw writer. Though she grew up in freehand. When not busy adding New England, today she makes faces to inanimate objects, he is Telephone (301) 215.8855 • Fax (301) 215.8863 www.hhmi.org busy worrying how long it will be her home near the much warmer © 2013 Howard Hughes Medical Institute shores of Hawaii, where she before he has to get a real job. The opinions, beliefs, and viewpoints expressed by authors in the HHMI Bulletin enjoys kayaking and traipsing He makes his home in Brooklyn, do not necessarily reflect the opinions, beliefs, up mountains with her husband NY, with his partner Annie and viewpoints, or official policies of the Howard Hughes Medical Institute. and dogs. their son Casper. Murphy Al MacIndoe, Graham Williams, Sarah Adolfsson, Mattias HHMI Bulletin / Fall 2013 3 President’s Letter Investing in the Basics not long ago, we had a health scare in my family. My sister was diagnosed with a rare disease. To make matters worse, her treatment caused a cascade of side effects that landed her in the hospital. No one in my family could understand why this was happening. So I went to Los Angeles and met with her doctor. After a lengthy discussion, I could finally piece together the trail of events that led to her illness and explain what was making my sister so sick.