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hhmi bulletin • howard hughes medical institute • www.hhmi.org • institute medical hughes howard • bulletin hhmi Spring ’15 Vol. 28 No. 2 4000 Jones Bridge Road Chevy Chase, Maryland 20815-6789 www.hhmi.org Address Service Requested bulletin Plant Pavers Jigsaw puzzle-shaped cells bulging with chlorophylls (red) cover the surface of leaves in many flowering plants. The fanciful pattern is in this issue more than just a whimsical quirk of nature, however. HHMI Investigator Neural Theory at Janelia Elliot Meyerowitz and his team have shown that, as plants grow, the Marta Zlatic in the Footlights indented regions and lobe-like outgrowths of these so-called pavement Bacterial Barcodes cells create internal stresses that reorganize cytoskeletal proteins. These microtubule proteins align along the cell walls (green), a process that in turn reinforces them against stress – evidence of a subcellular mechanical feedback loop. Learn more about the role of force in the development of animals, as well as plants, in “Show of Force,” page 12. Small Forces, vol. 28 / no. 2 no. / 28 vol. Big Impact Mechanical stress plays a vital role in the development Arun Sampathkumar and Elliot Meyerowitz Elliot and Sampathkumar Arun of both animals and plants HHMI Bulletin / Spring 2015 Observations Neuroscience, it turns out, is on the brink of its own “big data” revolution. Supplementing more traditional practices of small-scale hypothesis-driven laboratory research, a growing number of large-scale brain data collection and data aggregation ventures are now underway, and prospects are that this trend will only grow in future years. Mapping the roughly one hundred trillion synaptic connections of a human brain would by some estimates generate on the order of a zettabyte of data (a zettabyte over years of observation, Hubble reported corresponds to one million petabytes). a proportional relationship between redshifts For comparison, that’s about equal to the amount in the spectra of galaxies (interpreted as their of digital information created by all humans recession speeds) and their physical distances. worldwide in the year 2010. And recently Viewed in the context of cosmological models proposed efforts to map the human brain’s Albert Einstein and Willem de Sitter formulated functional activity at the resolution of individual earlier, these data strongly supported cells and synapses might dwarf even these cosmic expansion. This monumental insight numbers by orders of magnitude. The coming came from a dataset that comprised less than fifty data deluge is likely to transform neuroscience, data points, compressible to a fraction of a With Theory from the slow and painstaking accumulation of kilobyte. When it comes to applying theory to results gathered in small experimental studies “big data,” neuroscience, to put it mildly, Comes Order to a discipline more like nuclear physics or has some catching up to do. Sure enough, there The gray matter of the human brain astronomy, with giant amounts of data pulled in are many ways of analyzing brain data that are by specialized facilities or “brain observatories” useful and productive for extracting regularities may not be as physically vast as the dark that are the equivalent of particle colliders from neural recordings, filtering signal from matter of outer space. But the challenge of and space telescopes. noise, deciphering neural codes, identifying crunching astronomical data pales compared What to do with all this data? Physics and coherent neuronal populations, and so forth. to the complexity of parsing today’s deluge astronomy can draw on a rich and (mostly) But data analysis isn’t theory. At the time of of data about the brain. Making sense solid foundation of theories and natural laws this writing, neuroscience still largely lacks that can bring order to the maelstrom of organizing principles or a theoretical framework 12Like the creases in a sheet of origami paper, the stripes that pattern these of that torrent requires more than banks empirical data. Theories enable significant data for converting brain data into fundamental fruit fly embryos guide forces that will govern their shape. As an embryo of supercomputers, says computational reduction by identifying important variables knowledge and understanding. becomes longer and thinner, lines of protein are laid down along the growing neuroscientist and essayist Olaf Sporns. to track and thus distilling a torrent of primary fly’s head-to-tail axis. Each vibrant band consists of one of three members To achieve fundamental insights, he posits, data pulled in by sophisticated instruments into From The Future of the Brain: Essays by the World’s interpretable form. Theory translates “big data” Leading Neuroscientists, edited by Gary Marcus of the Toll receptor family. The receptors allow the cells to differentiate neuroscientists must do as astronomers do into “small data.” A remarkable example was and Jeremy Freeman. © 2015 by Gary Marcus and themselves from their neighbors and perform the directional movements and apply a theoretical framework to their the astronomer Edwin Hubble’s discovery of the Jeremy Freeman. Reprinted with permission necessary to remodel the growing embryonic tissue. Zallen Jennifer and Paré Adam Ngai Victo immense quantities of empirical data. expansion of the universe in 1929. Integrating from Princeton University Press. ContentsSpring ’15 Vol. 28 No. 02 Departments president’s letter 03 A Generation at Risk centrifuge 04 Making It Real 05 Craftsman bench report 06 Digging Deeper Beyond Itch 08 Autism’s Genetic Roots 10 Open and Shut Case perspectives & opinions 30 The Theory Connection 32 Q&A – What book have you read that influenced your work? chronicle 34 Science Education From Insight to Action 36 Toolbox Barcoding Bacteria 38 Lab Book T Cell Burnout Got Thirst? Here’s Why Salvaging SNAREs observations With Theory Comes Order Features 12 Show of Force Scientists are learning myriad ways that small forces add up to a big impact on the development of organisms, from plants to animals. 18 All the World’s a Stage Marta Zlatic is as capable All the World’s a Stage, page 18 of portraying the Greek heroine Hecuba as she is of pulling back the curtain on the neural circuitry of fruit fly larvae. At both pursuits, she’s won See a mouse drink with gusto www.hhmi.org/bulletin wide acclaim. Web-Only after a prompt from a light- triggered protein. Cover illustration: 24 Navigating the Torrent Content Martin Nicolausson Experimental neuroscientists Travel inside the body to Watch a zebrafish’s brain light experience an allergy-induced This paper is certified by SmartWood and theorists at Janelia are up as it takes a virtual swim. immune cell reaction. for FSC standards, which promote Kaplan joining forces to make sense environmentally appropriate, socially of – and improve – the deluge of Meir Witness tiny pores called Observe how mechanical forces beneficial, and economically viable Eli data coming out of labs. stomata develop on a leaf. can shape cells and tissues. management of the world’s forests. 2 Spring 2015 / HHMI Bulletin Contributors HHMI TRUSTEES Kurt L. Schmoke, Esq., Chairman President / University of Baltimore James A. Baker, III, Esq. Partner / Baker Botts. LLP Ambassador Charlene Barshefsky, Esq. Senior International Partner / WilmerHale Joseph L. Goldstein, MD Regental Professor & Chairman Department of Molecular Genetics University of Texas Southwestern Medical Center Garnett L. Keith Chairman & CEO SeaBridge Investment Advisors, LLC Fred R. Lummis Chairman & CEO Platform Partners, LLC Sir Paul Nurse, PhD President / The Royal Society Dame Alison F. Richard, PhD Senior Research Scientist & Professor Emerita Yale University Clayton S. Rose, PhD Professor Harvard Business School Anne M. Tatlock Retired Chairman & CEO Fiduciary Trust Company International HHMI SENIOR EXECUTIVE TEAM Robert Tjian, PhD / President Cheryl A. Moore / Executive V.P. & Chief Operating Officer Kathryn S. Brown / Head of Communications Sean B. Carroll, PhD / V.P. for Science Carrie Arnold (“Navigating Education Jennifer L. Farris / Head of Illustrator Graham Roumieu the Torrent,” page 24) is a Administrative Services (“Digging Deeper Beyond Itch,” freelance science and health writer Heidi E. Henning / V.P. & General Counsel page 6) is the creator of three living in Virginia. When she is Mohamoud Jibrell / V.P. for Information Technology faux autobiographies of Bigfoot. not writing about the living world Nitin Kotak / V.P. & Chief Financial Officer His work also has appeared in for publications like NOVA Next, Erin O’Shea, PhD / V.P. & Chief Scientific Officer The Atlantic, The New York Times, Scientific American, and National Gerald M. Rubin, PhD / V.P. & Executive Harper’s, an animated commercial Geographic, you can probably fnd Director, Janelia Research Campus for corn dogs, and elsewhere. her drinking coffee, cycling, Kathy A. Wyszynski / V.P. for Human Resources Landis Zimmerman / V.P. & knitting, or annoying the cat. Chief Investment Officer HHMI BULLETIN STAFF Mary Beth Gardiner / Editor Dana Cook Grossman / Story Editor Jim Keeley / Science Editor Nicole Kresge / Assistant Editor Friedman ADDITIONAL CONTRIBUTORS David Elaine Alibrandi, Michelle Cissell, Heather McDonald, Anne Sommer Pentagram Design / Design Arnold, Bryn Nelson (“Autism’s Allied Printing / Printing & Binding Genetic Roots,” page 8) is a former A photographer and flmmaker, Carrie microbiologist who decided he David Friedman (“The Theory would much rather write about Connection,”