FindingsFALL 2017 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of General Medical Sciences features 1 Protein Paradox: Enrique De La Cruz Aims to Understand Actin 18 The Science of Size: Rebecca Heald Explores Size Control in Amphibians articles 5 A World Without Pain 6 Demystifying General Anesthetics 10 There’s an “Ome” for That —TORSTEN WITTMANN, UNIVERSITY OF CALIFORNIA, SAN FRANCISCO ON THE COVER This human skin cell was bathed 17 Lighting Up the Promise of Gene Therapy in a liquid containing a growth factor. The procedure for Glaucoma triggered the formation of specialized protein structures that enable the cell to move. We depend on our cells 24 NIGMS Is on Instagram! being able to move for basic functions such as the healing of wounds and the launch of immune responses. departments 3 Cool Tools: High-Resolution Microscopy— Editor In Living Color Chris Palmer 9 Spotlight on Videos: Scientists in Action Contributing Writers Carolyn Beans 14 S potlight on the Cell: The Extracellular Matrix, Kathryn Calkins Emily Carlson a Multitasking Marvel Alisa Zapp Machalek Chris Palmer Erin Ross Ruchi Shah activities Production Manager 22 Superstars of Science Quiz Susan Athey Online Editor The Last Word (inside back cover) Susan Athey Find Us At Image credits: Unless otherwise credited, images are royalty-free stock images. https://twitter.com/nigms https://www.facebook.com/nigms.nih.gov Produced by the Offce of Communications and Public Liaison https://www.instagram.com/nigms_nih National Institute of General Medical Sciences National Institutes of Health https://www.youtube.com/user/NIGMS U.S. Department of Health and Human Services More stories on our Biomedical Beat blog https://www.nigms.nih.gov/fndings https://biobeat.nigms.nih.gov Protein Paradox: Enrique De La Cruz Aims to Understand Actin BY EMILY CARLSON But De La Cruz isn’t a profes- sional performer. He’s a molecular biophysicist at Yale University. The show-and-tell performance was part of a scientifc lecture on a paradox De La Cruz has studied for more than 10 years—how a chain of molecules, called actin, that is strong enough to support a cell can break so easily. “I beneft from seeing and holding things as much as anyone else,” he says, explaining that the props help people—even scientists—under- stand his research. By his own account, De La Cruz is an unlikely scientist. A frst- generation Cuban-American, he grew up in and around Newark, New Jersey. Few of his friends earned more than a high school — XIAOWEI ZHUANG, HARVARD UNIVERSITY, AND NATURE PUBLISHING GROUP diploma. De La Cruz never thought Actin (blue) and other proteins support a cell’s structure similar to the way bones he’d end up running his own lab at support our bodies. an Ivy League research university. As a young adult, he recalls, Enrique De La Cruz stood off to the side in a packed room. “It wasn’t even on my radar as As he waited for his turn to speak, he stroked the beads of a necklace. a possibility.” Was he nervous? Quietly praying? When he took center stage, the purpose Although discovering new details about biology keeps his job of the strand became clear. exciting, he said sharing lessons Like a magician—and dressed all in black—De La Cruz held up the he’s learned with students and other aspiring scientists makes necklace with two hands so everyone, even those sitting in the back, could it truly rewarding. see it. It was made of snap-together beads. De La Cruz waved the strand. It wiggled in different directions. Then, with no sleight of hand, he popped Inner City to Ivy League off one of the beads. The necklace broke in two. De La Cruz’s frst taste of research For the next hour, De La Cruz pulled out one prop after another: a piece came during his senior year of high school, when he participated in of rope from his pocket, a pencil tucked behind his ear and even a fresh a work-study program at a nearby spear of asparagus stuffed in his backpack. At one point, De La Cruz pharmaceutical company. He tested assembled a conga line with people in the front row. chemical compounds for their Findings | FALL 2017 1 effects on cholesterol in the blood- their shapes. The flaments also Instead of feeling like stream. Although the project was play a central role in muscle con- unrelated to what he studies now, traction. Because of these tasks, he didn’t belong, he De La Cruz said the experience the flaments must be strong. made science tangible, partly by Yet, the flaments can break. felt empowered to seek putting people and faces to In many cases, they must break the process. to carry out their functions. To out the knowledge and Because his parents—a welder assemble new chains, the flaments and a hospital pharmacist—instilled recycle their parts. Numerous guidance he needed in De La Cruz and his siblings the proteins facilitate this process in importance of education, he headed cells. Some of the proteins break to succeed. to college. But he stayed close to the flament chains to make more home. He applied only to Rutgers ends, which allows the chains to University. Interested in both shrink more rapidly and recycle medicine and teaching, De La Cruz parts faster. RESEARCHER ultimately decided to pursue a To investigate how actin flaments career doing research on basic life break, De La Cruz has relied heavily Enrique M. De La Cruz processes in an academic setting. on techniques, expertise and But his path to becoming a published papers from other felds. scientist almost hit a dead end “An hour in the library can save when De La Cruz started graduate a week in the lab,” De La Cruz says. school at Johns Hopkins University “There’s a lot of information already in Baltimore, Maryland. out there, and it’s always useful “On my frst exam—in a subject to look at others’ studies.” I wasn’t very familiar with—I scored Over the years, he and his team an 18.5,” he says. “The mean of the have pieced together many details class was an 88! I thought, ‘That’s on how actin flaments form it. I had my chance. This experiment and break. is over.’” “Curiosity is what gets you into His course instructor told him science and what keeps it fun,” —JEFF FOLEY, AMER ICAN HEART ASSOCIATION not to stress about the score and he says. “You’re going to know GRE W U P IN to work harder at the things he something in a few months that didn’t know. De La Cruz knew this you don’t know today.” Newark and Kearny, New Jersey was true: He had aced an exam Individual actin molecules, like JOB SITE in biophysical chemistry, a subject the pop-beads of the necklace, Yale University he was interested in and already string together with the help of salt. knew a lot about. The salt helps “glue” the chain links FAVORITE FOOD Instead of feeling like he didn’t together, De La Cruz explains. His mom ’-s Spanish style polenta belong, he felt empowered to seek By integrating computer models (harina de maíz) out the knowledge and guidance with biochemical and biophysical he needed to succeed. experiments, the De La Cruz team IF I WASN ’T A SCIENTIST I WOULD BE learned where the salt connects Managing a vinyl record shop to actin molecules. Each salt-actin Actin Action joint is tight, making the chain stiff, FAVORITE SONG Much of De La Cruz’s career has like the pencil prop De La Cruz “Do Anything You Wanna Do ” focused on studying actin, one of showed the crowd. But a protein by Eddie & the Hot Rods the most prevalent proteins on the called coflin can push off the salt, planet. Actin molecules form long, weakening the joint so it becomes thin chains that grow and shrink wiggly—De La Cruz demonstrated from the ends. These chains, or this with the rope—and more likely flaments, allow cells to move and to come apart. contract, and they help cells keep 22 National Institute of General Medical Sciences cool tools High-Resolution Microscopy— Filament breaks occur in Living Color where different sections BY ALISA ZAPP MACHALEK meet, similar to the way Cell biologists would love an asparagus spear to shrink themselves down and actually see, touch and hear cells’ snaps where the hard inner workings. Because that’s impossible, they have developed an ever-growing collection of part meets the soft, microscopes to study cellular innards from the outside. Using feshy part. these powerful tools, researchers can exhaustively inventory the molecular bits and pieces that make up cells, eavesdrop on cellular com- munication and spy on cells as they Because a flament has thousands The research team is now adapt to changing environments. of actin molecules and joints, some planning to use computer modeling In recent years, scientists have sections can be weak and wiggly, to better understand the specifc developed new cellular imaging while others are stiff. Filament roles of the wiggly and stiff techniques that allow them to breaks occur where different flament sections during the visualize cells’ contents in ways sections meet, similar to the way breaking process. They’ll test the and at levels of detail never before an asparagus spear snaps where modeling results with carefully possible. Many of these techniques the hard, woody part meets the designed lab experiments. soft, feshy part.