HHMI 2013 Year in Review

From the President

People say ideas are a dime a dozen—and it can seem that way today, in our information-rich world. But a big idea, well executed, remains something rare and special.

For 60 years, HHMI has empowered scientists to continually push the frontiers of biomedical research. We believe in big ideas. Our researchers are using the best new molecular tools to reveal brain activity, disease genetics, basic cellular activity, and more, in ways that transform our understanding of how biology works. In the classroom, our educators are matching this creativity with their own bold experiments in biology instruction, seeking to spark the next generation of scientists.

As we look ahead in 2014, we’re working hard to make the next big idea possible.

To back them up, we’re thinking big, too. Over the past year, we selected 27 new HHMI Investigators, announced $65 million in science education grants, and pledged $22.5 million over five years to the National Math and Science Initiative. In addition to funding, we’re providing free films for the classroom, and tools and software for any interested researchers to use. Our goal is to share resources and promote excellence at a scale that has meaningful and sustained impact across a wide swath of the science community.

And we’re not alone. HHMI is increasingly partnering with other funders to support basic science. With the Gordon and Betty Moore Foundation, we have supported leading plant scientists and will open a new, advanced imaging center for visiting scientists at our Janelia Farm Research Campus in the coming year. HHMI is also part of a new collaboration, the Science Philanthropy Alliance, that seeks to increase basic research funding at universities and research organizations across the United States.

As we look ahead in 2014, we’re working hard to make the next big idea possible. Please join us.

Signature Robert Tjian, President
Howard Hughes Medical Institute

2013 Highlights

How to Turn Genes On? Step by Step

A human’s 20,000 or so genes exist within a vast jumble of DNA. To work properly, each gene must be activated at the right time and place. Researchers know that a group of proteins assemble into a “pre-initiation complex” that triggers this process, but the exact molecular mechanisms have remained elusive. Using cryoelectron microscopy, HHMI Investigator Eva Nogales’ team captured first ever images of this cellular machinery, illustrating the stepwise assembly of this protein complex in structural detail.

Learn more about Nogales’ work in the HHMI Bulletin ›

Eva Nogales HHMI Investigator
University of California, Berkeley

Can UTeach? Training Grows

American students continue falling behind in the essential subjects of math and science. Fighting this trend, the National Math and Science Initiative works to significantly improve the number and quality of new K-12 teachers in the United States. In a White House briefing held in March, HHMI committed to invest $22.5 million over five years to expand the Initiative’s UTeach Program to an additional 10 research universities. These schools will graduate students who both major in math or science and are qualified to teach it.

In Support of STEM

Fewer than half the students who enter college intending to major in science, technology, engineering, or math (STEM) stick with it. HHMI is working to change that. We recently invited more than 200 U.S. research universities to apply for $65 million in science education grants to be distributed in 2014 as 35 awards of up to $2.5 million each. Our goal is to transform introductory courses by inspiring and equipping students to persist in STEM disciplines.

Innovators Named HHMI Investigators

In May, HHMI selected 27 of the nation’s top biomedical researchers to become Investigators. This new crop of HHMI scientists will receive $150 million, collectively, over the next five years to push the leading edge of basic research, asking hard questions and following unexpected discoveries. They join about 320 current HHMI Investigators at more than 70 universities, institutes, and other organizations nationwide. By investing in people, not projects, HHMI aims to advance science through its flexible support of talented individuals.

Learn more about HHMI’s new investigators in the HHMI Bulletin ›

Understanding Heart Defects

Every year, thousands of babies are born with severely malformed hearts. HHMI Investigators Richard Lifton and Christine Seidman are leading research efforts to explain why. They have found that about 10 percent of severe congenital heart defects are not inherited, but instead are caused by spontaneous mutations in the developing heart. The researchers found mutations in a variety of genes, many of them concentrated in a pathway that regulates key developmental steps.

Richard Lifton HHMI Investigator
Yale University

Christine Seidman HHMI Investigator
Brigham and Women’s Hospital

Team Targets Ataxia

Like Alzheimer’s disease, the lesser known spinocerebellar ataxia type 1 (SCA1) wreaks havoc in the brain as toxic proteins accumulate inside neurons. In SCA1, the toxic protein is ataxin-1. With support from an HHMI Collaborative Innovation Award, HHMI Investigator Huda Zoghbi assembled a team with diverse expertise to examine how hundreds of different genes affect ataxin-1 levels in neurons. The search led them to a single signaling pathway: RAS-MAPK-MSK1. Inhibiting the pathway in mice engineered to mimic the human disease reduced neurodegeneration in the animals, suggesting the team is on the right track.

Wheat Gene Fends Off Deadly Rust

Wheat is one of the world’s most important food crops—and perennially under attack by pathogens such as stem rust. Scientists have battled stem rust for decades by developing resistant wheat varieties that later become challenged as the fungus evolves. Now, HHMI-GBMF Investigator Jorge Dubcovsky has identified a wild wheat gene, Sr35, that elicits a strong immune response against a current, virulent form of stem rust. Breeding Sr35 into commercial wheat may provide a powerful defense in the war against this pathogen.

Learn more about plant defenses in the HHMI Bulletin ›

Jorge Dubcovsky HHMI-GBMF Investigator
University of California, Davis

Bright spots on an computer-generated image show nerve cell activity

Shine That Light Over Here

Scientists at Janelia Farm Research Campus have created a kind of molecular flashlight, GCaMP6, that tracks brain activity by lighting up when calcium is released during nerve cell signaling. This ultrasensitive tool allows scientists to image large groups of neurons as well as tiny cellular compartments with better resolution than previously possible. Janelia researchers work in small, interdisciplinary teams to advance brain research and imaging technologies.

Watch a video about GCaMP6 and the GENIE project team ›

Loren Looger, Karel Svoboda, Vivek Jayaraman, and Rex Kerr Janelia Group Leaders, GENIE Project
Janelia Farm Research Campus

Nobel for Cell Traffic Discoveries

HHMI Investigators Randy Schekman (right) of the University of California, Berkeley, and Thomas Südhof (left) of Stanford University, along with Yale University’s James Rothman, won the 2013 Nobel Prize in Physiology or Medicine for their discoveries detailing how molecules are ferried within and between cells. The three scientists each made major contributions toward solving the mystery of how a cell organizes its transport system to release insulin into the blood and move chemicals across the brain, among other biological activities.

Learn more about Schekman’s and Südhof’s work in the HHMI Bulletin ›

A t-cell is covered with small bright particles

Sizing Up HIV in the Body

How to quantify latent virus in HIV patients has been an important outstanding question in the field. HHMI Investigator Robert Siliciano led a team of scientists in a sobering discovery: the amount of HIV lying dormant in a patient’s body may be up to 60 times larger than previous estimates. The finding further complicates efforts to cure HIV/AIDS, as a significant percentage of these silent viruses can be reactivated once antiviral therapies are stopped. For researchers, the target just got bigger.

Coming Soon to a Classroom Near You

Few high school students have probed the mysteries of evolution in the Galapagos or wrestled with the structure of DNA, but now they can—through films. HHMI recently added four new short science documentaries to its free classroom offerings. Three of the films are part of The Origin of Species series, which follows naturalists traveling the world to understand how species form. The fourth film, part of a new series called Great Discoveries in Science, traces the quest to solve the structure of DNA. Each film comes with an extensive set of classroom materials, from hands-on activities to virtual labs.

Cancer Gene Caught in a Bind

For more than 30 years, the K-Ras gene has been at the top of the drug design target list. A mutant form of the gene is commonly implicated in human cancers but has been considered “undruggable.” In a major advance, HHMI Investigator Kevan Shokat and his lab group have identified a “pocket,” or binding site, in the K-Ras protein and designed a chemical compound that fits inside. The new inhibitor halts the activity of mutant K-Ras, yet leaves the normal protein untouched. This research could ultimately lead to molecularly targeted cancer therapies.

Awards & Honors

Südhof Honored with Lasker Award

HHMI Investigator Thomas C. Südhof of Stanford University and Richard H. Scheller of Genentech shared the 2013 Lasker Basic Medical Research Award, given by the Albert and Mary Lasker Foundation. Südhof and Scheller were honored for discoveries concerning the molecular machinery and regulatory mechanisms that underlie the rapid release of neurotransmitters. The Lasker Awards—considered among the most respected science prizes in the world—honor visionaries whose insight and perseverance have led to dramatic advances that will prevent disease and prolong life.

Lifton Wins Breakthrough Prize

The Breakthrough Prize in Life Sciences Foundation awarded HHMI Investigator Richard P. Lifton of Yale University and five other scientists the 2013 Life Sciences Prize for excellence in research aimed at curing intractable diseases and extending human life. The Breakthrough Prizes recognize pioneering work in physics and genetics, cosmology, and neurology and mathematics. Each prize carries an award of $3 million. Lifton, who has been an HHMI investigator since 1994, was honored for the discovery of genes and biochemical mechanisms that cause high blood pressure.

Elledge Receives Gairdner Award

In 2013, the Gairdner Foundation honored HHMI Investigator Stephen Elledge with a prestigious Canada Gairdner International Award in recognition of his contributions to medical science. Given annually, the Gairdner awards recognize scientists responsible for some of the world’s most significant medical discoveries. Elledge, who became an HHMI investigator in 1993, was honored for elucidation of the DNA damage response as a signaling network that controls DNA repair and genomic stability.

Learn more about Elledge’s work ›

Howard Hughes Medical Institute 2013 Year in Review