Member Tales

Enzymatic action

Cynthia Wolberger

Johns Hopkins University School of Medicine

Published September 28, 2020

Inside cells, DNA is coiled around histone proteins, making spools of nucleosomes. Cynthia Wolberger studies the molecular machines that unwrap the chromatin packing to transcribe or repair genes.

The structures reveal complicated biological mechanisms that involve an alphabet soup of chemical bonds, epigenetic tags, amino acid positions, several proteins, and multiple protein domains.

A recent study investigated the way in which a protein called ubiquitin that is attached to a histone helps an enzyme that attaches another type of chemical tag to the histone core of a nucleosome. For those new to the field, Wolberger suggests …

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Rules of motion

Priyamvada Acharya

Duke Human Vaccine Institute

Published July 31, 2020

Priyamvada Acharya studies how proteins on the surface of HIV move to invade cells and evade the immune system. For many years her research has been focused on the HIV-1 envelope (Env), a protein on the HIV-1 surface that the virus uses to enter human cells. In December 2019, she and her colleagues reported promising results of a new strategy that could lead to a long-sought vaccine.

Three months later, when the coronavirus pandemic was declared, the SARS-CoV-2 virus suddenly became an urgent target.

Acharya thought carefully about what her group at the Duke Human Vaccine …

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Cosmic Squared

Michael Cianfrocco

University of Michigan Life Sciences Institute

Published June 27, 2020

As one of best selling games of all time, Minecraft and its spinoffs are familiar to hundreds of millions of dedicated fans. But few people know about the video game’s legacy in cryo-electron microscopy.

To be sure, the legacy owes more to the required computing power than the game itself. By the time Michael Cianfrocco was a postdoctoral fellow, cryo-EM tools and techniques had advanced to near-atomic resolution. And the digital imaging data was creating a new technical problem to solve.

Cryo-EM required high-performance computers to convert the images of proteins into three-dimensional reconstructions. “There were …

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Kaps are Cool

Yuh Min Chook

University of Texas Southwestern Medical Center

Published April 28, 2020

Three weeks after most research on campus was paused in the first wave of the U.S. coronavirus pandemic, Yuh Min Chook learned that a cancer drug her group helped develop was going into a small global randomized clinical trial for hospitalized patients with COVID-19.

The drug works deep inside cells, blocking transport from the nucleus to the cytoplasm. As a cancer treatment, it seems to work by blocking the exit of native cancer-fighting molecules. Locked in the nucleus, the trapped proteins and RNA can counteract many oncogenic pathways that suppress tumors, growth, and inflammation.

In COVID-19, …

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Spiraling into focus

Carsten Sachse

Forschungszentrum Jülich

Published March 29, 2020

Some things take time and patience. Like generating higher atomic resolution structures from cryo-electron microscopy. Or reconstructing a protein’s hidden coils in atomic models. Or mastering the skills and teamwork in field hockey.

Carsten Sachse never played field hockey at the level of Germany’s world-dominating national team, but years of the sport in his youth helped shape his personality and work ethic. There’s the mix of a daily routine interspersed with intense match-ups. Rewards come from persistence and steady strategic steps toward a longer-term goal.

“To look at a topic from many different angles takes time,” …

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Seeing cilia

Alan Brown

Harvard Medical School

Published February 27, 2020

For sports buffs, the end of winter ushers in a new season of competitive delights. Alan Brown’s spring thoughts turn to Formula One and the pre-season test runs of new designs and rampant speculation among fans about which cars will have the edge in the coming months.

Powerful motors on an entirely different scale command Alan’s year-round attention. In his lab at Harvard Medical School (HMS) in Boston, Brown studies cilia, tiny hair-like projections on cell surfaces that propel algae and other microbes. A single cilium puts the wiggle into sperm. On other cells, cilia help …

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For the Love of EM

Guy Schoehn

Institut de Biologie Structurale, Grenoble, France

Published January 27, 2020

One day soon, the process of collecting data from cryo-electron microscopes may be as automated as it is on synchrotron beamlines. Until then, Guy Schoehn and his team will be busy training and collaborating with other researchers seeking technical EM expertise and insights.

Schoehn manages the EM platform at Institut de Biologie Structurale (IBS) in Grenoble, France. In December 2018, the institute upgraded its EM platform with a powerful new €2-million transmission electron microscope to support growing demand for higher resolution cryo-EM.

The new equipment marks a milestone for Schoehn and the institute. “We are quite …

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Protein Puddles

Michael Rosen

University of Texas Southwestern Medical Center in Dallas

Published December 16, 2019

A few years ago on a visit to Cape Cod, Michael Rosen was walking along the beach at low tide. He came across a tidal pool set in a giant rock. The pool was about the size of two science journals laid side to side. A large clump of insects floated on top.

He stirred the water with his hand, dispersing the bugs. Then he watched the individuals, probably 100 of them, begin to stick to each other in two and threes and eventually all cluster back together. “Each of them had six little legs that …

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Changing channels

Daniel Minor Jr.

University of California, San Francisco

Published September 27, 2019

Kissing a frog might not spark a fairy tale ending, but learning how frogs survive some of nature’s most deadly poisons has opened a new chapter in the laboratory of Daniel Minor Jr.

The potent neurotoxin saxitoxin, for example, can come from algae blooms in fresh, brackish, and oceanic waters, such as red tides, which seem to be on the increase from climate change and other factors. The toxin accumulates in clams, oysters, and mussels. If people eat contaminated shellfish, they can die within hours. Saxitoxin has a lethal dose a thousand times smaller than deadly …

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Listening Tips

Marcos Sotomayor

Ohio State University

Published July 30, 2019

When Marcos Sotomayor explains his research out loud, his voice tickles the topic of his studies. A core biological question in his laboratory addresses how hearing happens at the molecular level.

For words to be heard, sounds reach deep into a listener’s ear and vibrate bundles of hair-like projections called stereocilia. The bundles are perched atop hair cells, the sensory cells of the inner ear.

When the bundles move, channels open at the stereocilia tips. Potassium and other ions rush in, causing release of chemicals at the hair-cell base, where auditory nerves translate them to electrical …

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Hao Wu

A Higher Order

Boston Children's Hospital

Published May 30, 2019

Hao Wu is a third generation scientist whose formative years were shaped by the Chinese Cultural Revolution. In fact, it’s fair to say the revolution, better known for persecution of academics and intellectuals, gave an unlikely boost to her future career.

Wu’s parents were physicists, and her grandfather was a chemist for the previous government. Her father’s older siblings had emigrated to the United States. It all added up to a family judged as enemies to the revolution. In Beijing, young Wu was bullied by her peers. Her parents were ordered to the countryside to farm …

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The PARP Family Family

John Pascal

Université de Montréal,

Published February 28, 2019

Genetic damage can set the stage for normal cells to turn into cancer. So it may be surprising that blocking a DNA damage repair molecule can kill some cancer cells. John Pascal became intrigued by one of these molecules just as it came on the biomedical radar as a cancer target.

“Inhibiting PARP-1 is exquisitely toxic for cancer cells deficient in certain types of damage repair,” says Pascal, a structural biologist at Université de Montréal in Canada. “Normal cells can largely get by without it.”

Yet, it was unclear how PARP-1 contributes to DNA damage repair …

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Predicting Success

Bil Clemons

California Institute of Technology

Published December 18, 2018

For Bil Clemons, the first glimpse of a protein structure never gets old. “Seeing the electron density for the first time—it’s still just magical and one of the greatest experiences you can have as a scientist,” says Clemons, a biochemist at the California Institute of Technology (Caltech).

The crystal structure of Get4 bound to the N-domain of Get5 with the NMR spectra of the Get5 dimerization domain in the background. Image credit: Courtesy of B.Clemons

Those moments might be all the sweeter because of the months and years of trial and error that culminates in the …

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Curiouser and Curiouser

Ramaswamy Subramanian

Institute for Stem Cell Biology and Regenerative Medicine

Published November 27, 2018

One day, a recently retired colleague visited S. Ramaswamy in his University of Iowa laboratory and presented him with a fish from a Canadian lake and a question. Why was the fish blue? Normally, North American walleyes are golden yellow, but more seem to be turning blue in summer months.

The unexpected question hooked Ramaswamy, who goes by Rams, even though it had nothing to do with his core research program. But he places a high value on curiosity-driven research. “That has been the key to a lot of the work in the lab,” says Rams, …

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Proteins out of bounds

Gerhard Wagner

Harvard Medical School

Published September 27, 2018

As a physics undergraduate student in Munich, Gerhard Wagner worked on an esoteric atomic measurement of iron in a protein molecule. Then he heard from his supervisor, who was on sabbatical at Bell Labs in New Jersey. There, the same molecule, hemoglobin, the iron-rich protein that carries oxygen in red blood cells, was being probed by nuclear magnetic resonance (NMR) spectroscopy.

The technology caught Wagner’s attention. Why measure a single parameter, as he was doing, when you could measure many aspects at once with NMR and learn so much more, he asked himself. Little did he …

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Hiding in plain sight

Gaya Amarasinghe

Washington University in St. Louis

Published July 27, 2018

On a recent visit to the laboratory where he worked as an undergraduate, Gaya Amarasinghe thought about his scientific journey from student to professor. At first glance, his research interests seem to have drastically changed. Back then, he was studying signaling in cancer biology, and how oncogenes communicate within cells. Now, his group at Washington University in St. Louis investigates how some of the world’s deadliest viruses, such as Ebola, outcompete the host and cause disease.

Yet, he decided, not much has changed after all. “In the last 20 years, I haven’t done anything differently,” joked …

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Jumping Genes

Orsolya Barabas

European Molecular Biology Laboratory, Heidelberg

Published June 27, 2018

Thickly forested slopes define the environs around Heidelberg, Germany, the headquarters of the European Molecular Biology Laboratory. In her hillside EMBL laboratory, Orsolya Barabas probes the small pieces of moveable DNA that define the landscape of modern genomes.

Surprisingly few people have heard of transposons. These “jumping genes” have been flitting around genomes for millions of years, changing locations or introducing new copies of themselves all over the place in plants and animals. They escaped notice until the 1940s, when Barbara McClintock observed them in maize, where they dominate the DNA, eventually earning her a Nobel …

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Data Whisperer

Karolin Luger

University of Colorado Boulder

Published May 30, 2018

Like others in her sporty college town, Karolin Luger heeds the call of the mountains she can see from her laboratory at University of Colorado Boulder. Trail running and a daily 20-mile round-trip bike commute at altitude have kept her fit, but she would like to put to rest the rumors that she runs her research collaborators ragged on strenuous hikes. “All these crazy stories,” Luger says. “I only did that once.” And lately, she says, she’s the one who has a hard time keeping up on group outings.

Her collaborators can relax, but Luger wants …

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Flipping the Switch

Jacqueline Cherfils

École normale supérieure (ENS) Paris-Saclay

Published April 27, 2018

After graduate school, Jacqueline Cherfils attended a Jacques Monod Conference, a prestigious small scientific meeting in France named after a Nobel Laureate. She knew no one. Her goal: To find an interesting molecule to study in atomic detail. She listened to researchers talk about how proteins enter and exit cells. In the end, proteins called small GTPases caught her attention and have captivated it ever since.

“They are famous in biology, because they function as molecular switches in almost every living organism,” says, Cherfils, a National Center for Scientific Research (CNRS) research director at École normale …

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Tooling Around

Andrew Kruse

Harvard Medical School

Published March 29, 2018

Until recently, a vaccinated llama has been a membrane protein crystallographer’s best friend. That was before Andrew Kruse and his co-authors showed that yeast can be a faster, cheaper, and possibly better tool for otherwise impossible crystallographic studies.

Broadly, the Kruse lab at Harvard Medical School is interested in how cells transfer information across their membranes. To probe the finer points of the molecular interactions, Kruse and his collaborators have developed new tools, including the yeast platform and a new evolutionary approach, to make studies of these membrane proteins easier for themselves and others.

About 20 …

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Comings and Goings

Tom Rapoport, Ph.D.

HHMI, Harvard Medical School

Published February 23, 2018

Cell biologist Tom Rapoport may be best known for studies of how proteins get in and out of a convoluted compartment inside cells called the endoplasmic reticulum (ER). But his personal backstory rivals his scientific achievements as a Howard Hughes Medical Institute Investigator at Harvard Medical School (HMS). His life has been intimately shaped by major political persecutions and social upheavals of 20th century Europe and America. Here’s the short version:

“My father was born in Russia into a Jewish family that emigrated during the Russian revolution to Vienna,” Rapoport wrote in a 2010 essay. “[In] …

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Transcriptional Rhythm

Seth Darst

Rockefeller University

Published January 27, 2018

If the rhythm of bacterial genes being transcribed was set to music, it might sound like the asymmetric beat of Bartok, a favorite composer of structural biologist and pianist Seth Darst.

In bacteria, the core transcription enzyme making RNA from the DNA template rattles off about 20 nucleotides a second. But every 10 seconds or so, the swift RNA transcription pauses. Transcribing RNA from a gene may take 1-2 minutes, with half of that time spent on hold. The pauses happen at predictable intervals and are presumed to be important, but so far their function remains …

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The Language of Gene Regulation

Daniel Panne

European Molecular Biology Laboratory, Grenoble

Published November 21, 2017

To find an analogy for his studies of how genes are turned on and off, Daniel Panne turns to the prehistoric drawings he viewed on a recent family vacation. The famous Lascaux Cave is a half-day’s drive from Grenoble, France, where he has headed a research group for nine years at the European Molecular Biology Laboratory (EMBL). Scenes of horses, stags, and other images depicted on cave walls and ceilings showcase some of the earliest examples of human art and thought.

“Some linguists consider such examples of abstract symbolic reasoning as an indication of the ability …

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Not Your Average Protein

James Fraser

University of California, San Francisco

Published October 23, 2017

Like many of James Fraser’s scientific interests, his lab motto, “Beer and Tacos,” arises from baseball statistics. A sports writer invoked the beer-and-tacos analogy to describe the false dichotomy between statistical analysis—such as in the book and movie Moneyball—and traditional scouting by observation. It’s not an either-or scenario. The modern ball club—and scientist—needs both.

In the Fraser lab at University of California, San Francisco, the motto applies widely. It covers their routine practice of posting a preprint manuscript at the same time they submit a paper for publication. Online preprints speed results to other scientists, and …

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Message Received

Sebastien Granier

French National Institute of Health and Medical Research (INSERM), Institut de Génomique Fonctionnelle, Montpellier France

Published August 24, 2017

As an undergraduate at University of Montpellier in France in the early 2000s, Sébastien Granier’s interest in science was stoked by the passionate lectures of a renowned plant physiologist who studied the architecture of trees, and tropical forest canopies in particular. Soon his attention was drawn to the dramatically scaled down world of G-protein coupled receptors (GPCRs) and their crucial role in cell-to-cell communication and human health.

Granier has been riveted by GPCRs ever since. The family of receptors scattered in cell membranes throughout the body detect a staggering range of signals outside the cell and …

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Resistance is Futile

Celia Schiffer

University of Massachusetts Medical School

Published July 28, 2017

Celia Schiffer | University of Massachusetts Medical School

Approximately 200 million people are infected with hepatitis C virus (HCV) worldwide. While novel drugs, such as protease inhibitors, are effective against the virus, resistance to them evolves rapidly.

In 2016, however, Celia Schiffer, professor of biochemistry and molecular pharmacology at the University of Massachusetts Medical School, applied a smart drug development approach to the design of new HCV protease inhibitors. The strategy, which she developed a decade ago, minimizes the emergence of resistance by using structural biology and other tools to guide the design of chemicals that …

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Twist of Fate

Leemor Joshua-Tor

Cold Spring Harbor Laboratory

Published June 28, 2017

Leemor Joshua-Tor got her first introduction to chemistry in 7th grade. The Weizmann Institute of Science had created an introductory chemistry class for the local middle school in Rehovot, Israel, where Joshua-Tor was a student. The class was memorable not only for the science, but also because the box she used to store the cards she’d made representing the elements on the periodic table was one of her mother’s perfume boxes. “Every time I opened the box it had this nice smell, so I think my brain associated that smell with science,” says Joshua-Tor, a structural …

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Drug Designer

John Buolamwini

Rosalind Franklin University of Medicine and Science

Published May 30, 2017

In his lab at the Rosalind Franklin University of Medicine and Science in North Chicago, John K. Buolamwini designs drugs. He’s currently focused on reformulating drugs called nucleoside analog drugs, which have been used to treat HIV, hepatitis B, and pancreatic cancer. The drugs have been effective, but cause mitochondrial toxicity that limit their use in HIV/AIDS.

“If we can protect the mitochondria in the presence of these drugs, they can be resurrected as therapies,” says Buolamwini, a medicinal chemist and Chair of the department of Pharmaceutical Sciences. “That excites me.”

Buolamwini grew up in Ghana, …

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Fixer Upper

Brandt Eichman

Vanderbilt University

Published February 27, 2017

Soon after starting his lab at Vanderbilt University in 2004, Brandt Eichman attended a DNA repair meeting in Bermuda. When the Keynote speaker mentioned two new glycosylases, enzymes that recognize and repair damaged DNA, Eichman scribbled the names in his notebook: AlkC and AlkD.

Back in Nashville, Eichman, who had studied glycosylases as a post-doc, noticed that the genetic sequences of these glycosylases didn’t look like any others he’d seen. His lab found that the structure of AlkD also looked different. “It didn’t look like any other DNA binding protein in the database,” says Eichman, professor …

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Mobilizers

Phoebe Rice

University of Chicago

Published January 31, 2017

A few years ago, at a New Year’s Eve party in her neighborhood, Phoebe Rice mentioned, as you do, that she needed some methicillin-resistant Staphylococcus aureus (MRSA) strains.

A neighbor responded: “Have you met Bob and Susan?”

They had a freezer-full and were willing to share. Soon after, Rice, professor of biochemistry and molecular biophysics at the University of Chicago, began investigating the mobile elements of DNA that give Staph its methicillin-resistance capability.

Initially she focused on the DNA recombinase protein that allows the mobile element, a type of genomic island, to insert itself into the …

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Escape Artist

Katya Heldwein

Sackler School of Graduate Biomedical Sciences at Tufts University

Published December 19, 2016

Katya Heldwein’s first investigations of herpesviruses focused on how they get into host cells. In the process, she became interested in how these viruses get back out again. Herpesviruses replicate their genomes in the cell’s nucleus and package them in capsids. But these capsids are too large to pass through the nucleus membrane pores. “It wasn’t clear how they were getting out,” says Heldwein, associate professor of molecular biology and microbiology at Tufts.

So in 2016, she solved the structures of two viral proteins involved in the process. The work helped her figure out that the …

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Nature’s Confectioner

Jochen Zimmer

University of Virginia

Published November 29, 2016

In early 2016, Jochen Zimmer published a series of structural snapshots of molecular machinery during different stages of assembly and secretion of cellulose across the cell membrane. The series of images reveals a two-part system; one part of the machinery repeatedly adds on to the polysaccharide and another, a helix that acts as a lever, advances it. Zimmer, an associate professor of molecular physiology at the University of Virginia, even engineered a minuscule tether to tie back the lever to verify that this would, indeed, stall the transport process.

The work is part of a collection …

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State of Fusion

Jason McLellan

Geisel School of Medicine, Dartmouth College

Published October 27, 2016

Viruses like human immunodeficiency virus (HIV), respiratory syncytial virus (RSV), and influenza have proteins on their surface that undergo dramatic conformational changes and allow the virus to fuse with a host-cell membrane and infect the cell. Jason McLellan, Assistant Professor of Biochemistry and Cell Biology at the Geisel School of Medicine at Dartmouth College, specializes in understanding these fusion proteins. He applies what he learns to develop new ways to stop the proteins from being triggered to change shape and cause infection.

Early on, McLellan planned on going to medical school, but organic chemistry labs had …

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Here Be Dragons

Brian Fox

University of Wisconsin, Madison

Published September 28, 2016

In recent work, Brian Fox and colleagues at the Great Lakes Bioenergy Research Center at the University of Wisconsin-Madison characterized glycoside hydrolases, enzymes that digest cellulose and can be used to turn plants such as switch grass into biofuels. These enzymes occur in nature with a wide range of diversity. Genomic variations yield over thousands of unique proteins that maintain a similar core function, but with a range of sweet spots for temperature, acidity, and substrate preference.

A key focus of the Center, which collaborates with other labs, including the Joint BioEnergy Institute, Sandia National Laboratories, …

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Pharm Team

Oleg Tsodikov

University of Kentucky College of Pharmacy

Published August 24, 2016

Heading a small lab of just three people at the University of Kentucky College of Pharmacy, Oleg Tsodikov, the only structural biologist at the College, is juggling multiple drug discovery projects. “It’s a small structural biology community here, but with good facilities,” says Tsodikov, Associate Professor of pharmaceutical sciences at the University of Kentucky (UK).

The project that is farthest along involves the discovery of small molecules for use in combination with drugs of last resort for extensively drug-resistant tuberculosis infections. These small molecules interrupt the pathway that confers resistance to aminoglycoside drugs such as kanamycin. …

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Spiro-Gyra

Alejandro Buschiazzo

Institut Pasteur, Montevideo, Uruguay

Published July 27, 2016

When Alejandro Buschiazzo took on the responsibility of building a structural biology core facility in Latin America, he was taking a risk. He was an assistant professor at the Institut Pasteur in Paris, and his career as a structural biologist had only just begun. Plus the institute he was moving to, the Institut Pasteur in Montevideo, Uruguay, was also brand new.

But to Buschiazzo, the risk was worth it. “Structural biology is quite underdeveloped in Latin America, from Mexico down,” he says. “So this was very exciting for me. It was a risk, but it was …

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Big Questions, Big Answers

Jennifer Doudna

University of California, Berkeley

Published February 22, 2016

Jennifer Doudna has reached celebrity status as one the inventors of the CRISPR/Cas9 genome editing technology. The tools, the equivalent of a toolkit for performing precision surgery on the DNA of any organism, have revolutionized research in the biological sciences and could do the same for medicine in the near future. It is work related to CRISPR that intrigues her most right now, but not so much in terms of directly advancing the tools. Rather, Doudna is — and has always been — interested in the fundamentals.

“Fundamental research is critical for everything we do,” says …

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Not a Structural Biologist

Enrico Di Cera

Saint Louis University

Published December 17, 2015

Enrico Di Cera studies proteins involved in blood coagulation. He has spent a significant portion of his career working out the function and structure of thrombin, and has recently solved the first structure of prothrombin, thrombin’s precursor in the body.

Conformational plasticity of prothrombin. The three structures are aligned over the rigid kringle-2/protease pair and then visualized separately in the same orientation. Individual domains are labeled and colored as follows: Gla domain (Gla, blue), kringle-1 (K1, red), kringle-2 (K2, green), A chain (Ac, orange), B chain (Bc, yellow). The flexibility of Lnk2 causes the Gla domain/kringle-1 …

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Divide and Conquer

Kevin Corbett

University of California, San Diego

Published November 19, 2015

Kevin Corbett got his start washing dishes. The job, at TechLab Inc., a small biotech near Virginia Tech, led to research investigating the life cycle of a parasitic amoeba at the University of Virginia, where he was a biochemistry undergraduate.

Later, in the spring of 2000, he walked into the office of the late Don Wiley at Harvard for his first graduate school interview. “He sat me down in front of a Silicon Graphics workstation, gave me a pair of 3D glasses, and for the first time I saw how a protein was built,” says Corbett, …

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Trans-Plant

Gang Dong

Max F. Perutz Laboratories at the Medical University of Vienna

Published September 26, 2015

After finishing his postdoctoral research at the Yale School of Medicine in 2008, Gang Dong moved his family to Vienna, Austria, to start his own research group at the newly established Max F. Perutz Laboratories (MFPL) at the University of Vienna and the Medical University of Vienna. He had no apartment and didn’t speak German, and the relative who had been helping them with their three-month-old daughter had moved back to China. “The first few months were very hard for me and my family,” says Dong, Junior Group Leader at MFPL.

Since then, Dong has established …

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Keep on Moving

James Berger

Johns Hopkins School of Medicine

Published August 23, 2015

Say I’ve got two related motor proteins, says James Berger, professor of biophysics and biophysical chemistry at the Johns Hopkins School of Medicine, both helicases. One, which is responsible for DNA replication, moves at high speeds, up to 1000 base pairs per second. The other, involved in transcription, plods along at 30 bases per second. These proteins share a common ancestor, but have very different physical behaviors. “Why?” he asks. “What is it in the structure that encodes that maximum speed limit at which the motor can move? I would argue that you can look at …

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Totally Tubular

Antonina Roll-Mecak

National Institutes of Health

Published July 27, 2015

Antonina Roll-Mecak was an accomplished pianist when she moved to New York from Romania, but she came for the science, specifically to study chemical engineering at Cooper Union. “I loved math and music. Those two things were encouraged in my family,” she says.

Now Roll-Mecak is applying her mathematical mind to cell biology in an effort to crack the tubulin code. Tubulin proteins form hollow tubes inside cells called microtubules that provide cytoskeletal structure and also act as a highway system for cellular traffic. The tubulin code refers to post-translational modifications to tubulin that are thought …

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From Disorder, Function

Julie Forman-Kay

The Hospital for Sick Children, University of Toronto

Published June 29, 2015

After earning a chemistry degree at MIT in 1985, Julie Forman-Kay headed to Yale for graduate work in the lab of structural biology pioneer Fred Richards. Forman-Kay – who says she never grew out of asking “Why?” – had found an ideal mentor. “He was a wonderful scientist who was more interested in questions than techniques,” she says.

The question that stuck with Forman-Kay concerned protein dynamics and disordered states. Though she was initially interested in protein structures, she later realized that many proteins and protein regions function in the disordered state, so over time, her …

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Two Labs, Many Methods

Michael Sattler

Technical University Munich, Helmholtz Zentrum München

Published April 28, 2015

Two Labs, Many Methods Michael Sattler / Technical University Munich, Helmholtz Zentrum München

In 2011, Michael Sattler took a look at an RNA binding protein that was known, based on earlier X-ray crystallography work, to have a structure with a specific arrangement of two RNA binding domains bound to its RNA ligand. Using nuclear magnetic resonance (NMR) spectroscopy, however, he found at least two different arrangements of the two domains in the protein: one open, one closed, neither resembling that of the crystal structure. “The crystallography missed that there are closed and open states. It’s something …

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Picture This

Georgios Skiniotis

University of Michigan Life Sciences Institute

Published March 20, 2015

When Georgios Skiniotis arrived at the University of Michigan Life Sciences Institute in 2008, his first task as a new professor was to build a cryo-electron microscopy lab. Since then, he’s made good use of it. His work has contributed to Nobel Prize-winning research, and in his own lab, he uncovered the inner workings of polyketide synthases, natural enzymes that act as factories to assemble complex chemicals that have antibiotic and anticancer properties. “We’re planning on using this knowledge to redesign these machines to create new novel molecules that might have pharmaceutical applications,” says Skiniotis, an …

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Intron Intrigue

Navtej Toor

University of California at San Diego

Published February 20, 2015

When Navtej Toor started searching for a post-doc in 2004, he applied to just one lab, that of Anna Pyle at Yale University. It was a long distance from the University of Calgary, where he’d done his undergraduate and graduate studies in biochemistry, and a far cry from his nearby rural hometown of Sparwood, British Columbia. But Pyle’s interests most closely resembled his own.

Toor, now an assistant professor of chemistry and biochemistry at the University of California, San Diego, had become interested in RNA as an undergrad. Later, when he saw the high-resolution structures of …

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Cut and Paste

Martin Jinek

University of Zurich

Published January 28, 2015

In January 2013, Martin Jinek published a paper in eLife showing that the CRISPR endonuclease Cas9, molecular scissors that silence the DNA of invading viruses in bacteria, could also be used to edit the DNA in human cells. The work coincided with similar findings from George Church at Harvard Medical School and others, and helped launch the CRISPR gene editing revolution.

The key discovery, however, had come a few months earlier, the result of basic scientific curiosity. Jinek, then a postdoc in the lab of Jennifer Doudna at the University of California at Berkeley, had become …

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Basics and Beyond

Qing Fan

Columbia University

Published December 18, 2014

As a chemistry graduate student at Harvard University, Qing Fan made the rounds of laboratory open houses. She stopped after she saw a short talk by the late Don Wiley about how major histocompatibility complex (MHC) molecules are able to recognize and differentiate a large range of antigens. “It is a very elegant mechanism, and I was fascinated,” says Fan, assistant professor of pharmacology and pathology and cell biology at Columbia University.

She joined Wiley’s lab immediately. “Don Wiley pioneered the use of structural biology and structural methods to provide insights into biological problems,” she says. …

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Bloodletting and Other Studies

Pedro José Barbosa Pereira

Institute for Molecular and Cell Biology, Portugal

Published November 25, 2014

When searching for a graduate program, Pedro José Barbosa Pereira was drawn to the lab of Nobel Laureate Robert Huber at the Max Planck Institute of Biochemistry in Munich for obvious reasons. But it was the leeches that made him stay.

The laboratory was beginning to explore anticoagulation factors that allow creatures like leeches and ticks to survive. “Leeches can feed twice a year and keep the meal liquid in their guts for six months. This is absolutely incredible,” says Pereira. “How do they do it?”

Pereira later ended up on a different project, but that …

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In Search of…New Drugs

Doug Daniels

Broad Institute

Published September 30, 2014

When Doug Daniels finished his chemistry degree at the University of Michigan and set off for The Scripps Research Institute for graduate study, he’d already made a key career decision. "I decided I was more interested in the discovery and development of drugs than in the practice of prescribing them," he says.

Having ruled out medicine or even an MD/PhD program as a way forward, he instead dove into structural biology. He’d come to love organic chemistry in college, but it was the visual aspects of how structure relates to reactivity that hooked him. "I wanted …

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An Affinity for Affinity…and Corals

John C. Williams

City of Hope

Published August 29, 2014

As a post-doc at Columbia University, John Williams and his wife-to-be wanted a pet. They ended up with the unlikeliest of companions. "We started a reef tank," says Williams.

Williams, now an associate professor of molecular medicine at City of Hope, noticed that all of his corals closed up when he cut one for propagation, a sign that the corals were releasing powerful chemicals. Having trained as a chemist, he recognized the potential for therapeutic leads in his aquarium, but his actual career — that of becoming a crystallographer with a yen for curing cancer — …

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Piotr Sliz, Ph.D.

Principal Investigator, SBGrid

Published August 1, 2014

The Natural Bridge
In 2013, Piotr Sliz and the team at SBGrid published a paper in eLife describing, for the first time in a formal, academic fashion, the SBGrid model. In existence since 2000, SBGrid now has a life of its own, with 250 members and several employees supporting its operations. “We have an excellent team in place,” says Sliz, SBGrid’s founder and director. “It’s almost self-propelling.”

But turning SBGrid into an international consortium hasn’t been Sliz’s only focus. During these past ten-plus years, he has advanced computing at HMS, expanded SBGrid beyond X-ray crystallography to …

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Membrane Master

Tamir Gonen

HHMI Janelia Farm

Published June 30, 2014

In college at the University of Auckland in New Zealand in the early 1990s, Tamir Gonen’s business classes bored him so much that he had his sister enroll him for his future classes. She put him on her track – medicine – and he never looked back.

Gonen, now a Group Leader at the at Howard Hughes Medical Institute’s Janelia Research Campus, completed his bachelor’s degree in inorganic chemistry and biochemistry with First Class Honors. He focused his research on the lens of the eye, a clear tissue nourished not by blood vessels but by a …

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The Natural Bridge

Piotr Sliz

Harvard Medical School

Published June 13, 2014

In 2013, Piotr Sliz and the team at SBGrid published a paper in eLife describing, for the first time in a formal, academic fashion, the SBGrid model. In existence since 2000, SBGrid now has a life of its own, with 250 members and several employees supporting its operations. “We have an excellent team in place,” says Sliz, SBGrid’s founder and director. “It’s almost self-propelling.”

But turning SBGrid into an international consortium hasn’t been Sliz’s only focus. During these past ten-plus years, he has advanced computing at HMS, expanded SBGrid beyond X-ray crystallography to include electron microscopy …

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Surprise, Surprise

Catherine Drennan

Massachusetts Institute of Technology

Published April 26, 2014

After studying chemistry at Vassar College, Catherine Drennan took a leap from her native New York to a Quaker-run farm school in Iowa. Being the high school’s only science teacher, she taught physics, chemistry, and biology, which included monitoring pregnant hogs and assisting them through labor. "I call it real biology," she says. "At one time, I could tell you all of the signs that a hog was going into labor."

For chemistry, however, that sense of real — the ways in which chemistry could solve problems in the world — wasn’t clear. So Drennan decided …

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Gone Viral

Olve Peersen

Colorado State University

Published March 20, 2014

After studying membrane proteins in an NMR lab as an undergraduate at Carnegie Mellon University, Olve Peersen went to Yale for graduate school. The year was 1988, the heyday of crystallography at Yale, yet Peersen, for the most part, steered clear of it. "I was focused on membrane proteins and NMR, and perhaps a bit brainwashed," he says.

But the brainwashing didn't last. In fact, Peersen, who is now professor of biochemistry and molecular biology at Colorado State University, eventually found crystallography and uses it and several other tools (though not NMR) in his lab today. …

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Vacc-elerator

Peter Kwong

Vaccine Research Center, NIH

Published December 17, 2013

Peter Kwong was putting the finishing touches on his work at the University of Chicago solving the structure of ?-bungarotoxin, a neurotoxin in snake venom, when structural biologist Wayne A. Hendrickson called from Columbia University. "Would you be interested in working on CD4?" he asked.

The year was 1987. Kwong, who was doing graduate research in the lab of the late Paul B. Sigler, a pioneer in structural biology, was in the process of moving to Yale.

At the time, CD4, the receptor for the human immunodeficiency virus, was so new that Kwong hadn't even heard …

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Structural Storyteller

Karin Reinisch

Yale University

Published November 15, 2013

Karin Reinisch had being doing structural biology since graduate school, and as a post-doc solved the reovirus core in the lab of Stephen Harrison. But it wasn't until she arrived at Yale in 2001 to set up her own lab that she found her niche. "At least half of the department, six or seven people at the time, were working in one particular area, how you move materials between different organelles," she says. "That made it a very rich environment for a structural biologist."

Even today, Reinisch, now associate professor of cell biology at the Yale …

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Inside the Box

Mishtu Dey

University of Iowa

Published September 17, 2013

They say the shoes make the man. For Mishtu Dey, assistant professor of chemistry at the University of Iowa, the shoes made the science.

In 2007, during the last year of her postdoc at the University of Michigan, Dey told her mentor, Steve Ragsdale, that she wanted to crystallize the enzyme she was studying, methyl-coenzyme M reductase (mcr), the only enzyme found in nature that produces methane. Ragsdale, who isn't a crystallographer, gave her the go ahead. "He didn't think I'd actually do it," she says.

The trouble was that oxygen inactivates mcr so that …

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Sensing a Change

Brian Crane

Cornell University

Published August 16, 2013

Brian Crane was all set to stay in Canada to attend graduate school when he heard about a new program at the Scripps Research Institute billed as graduate studies "at the interface of chemistry and biology." In 1990, such integrated programs were just emerging, so Crane, a chemist with biochemistry leanings, was intrigued. He had never heard of Scripps, being himself from Manitoba, in Winnipeg, but after a visit to the California campus, he decided the program was a perfect fit.

"The emphasis was chemical, but it had a biology culture," he says. "More freeform and …

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Towards Personalized Oncology

Mark Lemmon

University of Pennsylvania (now at Yale School of Medicine)

Published July 16, 2013

Mark Lemmon's career in structural biology began with a decision not to pursue structural biology. At Oxford University as an undergraduate, he'd been drawn to understanding biochemistry at a structural level. But the thing he wanted to understand most, transmembrane signaling, posed a problem. "In the late 1980s, solving crystal structures of membrane proteins wasn't something one could expect to do," says Lemmon, George W. Raiziss Professor of Biochemistry and Biophysics at the University of Pennsylvania.

So he decided to study membrane signaling using molecular instead of structural techniques. His graduate work at Yale University involved …

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Brush with Fame

Yizhi Jane Tao

Rice University

Published June 14, 2013

In 2006, Yizhi Jane Tao accepted an award for being one of the most influential Chinese at her undergraduate alma mater, Peking University. Other awardees included Oscar-winning director Ang Lee and actress Zhang Ziyi, who starred in Crouching Tiger, Hidden Dragon.

"It was good to see that our work is appreciated," says Tao, associate professor in biochemistry and cell biology at Rice University. "But it made me realize that fame is not important to me. I like my work better."

Tao studies viruses, specifically RNA viruses. She got her start working with bacteriophages in graduate school …

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Toxic Avenger

Borden Lacy

Vanderbilt University

Published May 21, 2013

While the bacterial toxin that causes anthrax has been used as a deadly biological weapon, from a scientific point of view, it has an upside. "The nice thing about anthrax is that separate proteins make up the toxin," says Borden Lacy. "So long as you keep them apart, it's entirely safe."

If there are nice things to say about other bacterial toxins, she will likely know them. They are her specialty.

Lacy, an associate professor of Microbiology at Vanderbilt University, began her studies of toxins in graduate school at the University of California, Berkeley by …

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Pushing the Boundaries

Stephen Harrison

Harvard Medical School

Published April 22, 2013

In the mid-1960s when Stephen Harrison began to determine the structure of the tomato bushy stunt virus, SBGrid didn't exist. There was no need for it. They didn't even have a hard disk for storage.

"Near the end of the 60s they got a disk. That was a big deal," recalls Harrison, Giovanni Armenise-Harvard Professor of Basic Medical Sciences at Harvard Medical School. "One disk."

Lacking storage and a network, as a doctoral student in biophysics at Harvard, Harrison had to walk to the Computer Center to code his programs on punch cards. The limiting factor, …

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Strength in Numbers

Joseph Ho

Academia Sinica, Taiwan

Published March 18, 2013

In graduate school at Boston University, Meng-Chiao (Joseph) Ho nearly quit science. He had chosen to focus on a difficult problem, solving a perfectly twinned protein crystal without a homology model to use for phases. His mentor, Karen Allen, a biochemist and crystallographer, had already spent 12 years trying to solve the structure. After 5 more years and no results worth reporting, Ho had a choice: graduate without a paper to his name or give up.

"I almost became a chef," says Ho, who is now an assistant research fellow at the Institute of Biological Chemistry, …

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One Lab, Many Methods

Wesley Sundquist

University of Utah

Published February 12, 2013

Wes Sundquist got his first taste of structural biology as a doctoral student in chemistry at MIT in Cambridge, MA, designing small molecules to bind to DNA and using nuclear magnetic resonance imaging and crystallography to look at them.

"The more I looked at the molecular biology, the more the biomolecules interested me," says Sundquist, professor of biochemistry at the University of Utah. When Sundquist completed his degree in 1988, he swapped one Cambridge for another, spending the following 4 years as a post-doctoral fellow at the Medical Research Council Laboratory of Microbiology at Cambridge University, …

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From Actin to Action

Emil Pai

University of Toronto, Canada

Published January 11, 2013

Emil Pai trained as a classical chemist in the mid-1970s at the University of Heidelberg. He spent his time learning messy, inefficiently named chemical reactions. "A 60 percent yield was cause for celebration," he says.

Then he attended a lecture on enzyme catalysis, a way to perform very precise biochemical reactions. "For a chemist, it was a humbling experience," says Pai. "I realized that to understand these reactions, you have to know what the molecules look like." Pai, now a professor of biochemistry, medical biophysics and molecular genetics at the University of Toronto (and also former …

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X-PLORer

Axel Brunger

Stanford University

Published October 1, 2012

Axel Brunger joined SBGrid in the early days, in 2006, but he may be best known among structural biologists as the man behind CNS (the Crystallography & NMR System), which he contributes to SBGrid, among other tools. Today, however, Brunger focuses almost all of his work on understanding the molecular mechanism that causes neurons to release neurotransmitters and propagate nerve signals.

"Most drugs for treating neurological diseases affect postsynaptic signaling," says Brunger. "If we could develop compounds that could act on the actual release, that could open up a range of more specific and finely tuned …

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Share the Wealth

Zbyszek Otwinowski

University of Texas Southwestern

Published August 22, 2012

When Zbyszek Otwinowski, who joined SBGrid in the Spring of 2012 along with 8 other laboratories at the University of Texas Southwestern, came from his native Poland to the United states 31 years ago, structural biology was not on his radar. He had come to the University of Chicago to study physics.

But just two years later, he met the late Paul Sigler, a pioneer in crystallography, who worked on the structure of RNA and regulatory complexes. After that, Otwinowski's path shifted away from physics and towards biology. Otwinowski, now a professor of biochemistry at …

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Unraveling RNA

Anna Pyle

Yale University

Published July 18, 2012

As a child growing up near Sandia National Laboratory in New Mexico, surrounded by physicists and chemists, Anna Pyle had an unconventional sort of chemistry set. Among her playthings was a cube of depleted uranium (only "slightly radioactive," she says). With the language of science as much a part of her life as English, Pyle, now William Edward Gilbert Professor of Molecular, Cellular and Developmental Biology and Professor of Chemistry at Yale University, chose to study chemistry as an undergraduate.

It wasn't until graduate school at Columbia University that biology grabbed her attention. She began by …

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Creative Copy Cat

Pamela Bjorkman

California Institute of Technology

Published April 25, 2012

For several years now, the lab of structural biologist Pamela Bjorkman, Max Delbrück Professor of Biology at California Institute of Technology, has been trying to find a new way to stop HIV with antibodies that prevent the virus from infecting a cell.

Normally, the body forms antibodies on its own. But in the case of HIV, which mutates rapidly and has few handholds for antibodies to grab onto, scientists have had trouble uncovering natural antibodies. Only recently have the numbers of natural neutralizing HIV antibodies been significant enough to enable researchers to compare them with …

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From Curiosity to Cure

Marc Kvansakul

La Trobe University, Australia

Published December 13, 2011

Marc Kvansakul decided to become a structural biologist as a young teen after watching a documentary that described proteins as assemblies of Lego-like blocks. Today Kvansakul’s newly formed lab in the department of biochemistry at La Trobe University in Victoria, Australia, is using what he has learned about the sequences and structures of anti-apoptotic viral proteins to start developing new treatments for Burkitt lymphoma, a form of the disease known to be caused by the Epstein-Barr virus.

Not exactly the same as building yellow and red plastic-brick scale models, but, says Kvansakul, “it’s all very good …

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Crystallography for Kids

Lynne Howell

The Hospital for Sick Kids, University of Toronto, Canada

Published May 17, 2011

Most people, armed with tartar-control toothpaste and a miniature scrub-brush, do battle with biofilms every morning. Biofilms form when bacteria attach to a surface, like a tooth, and form a colony encased in a protective coating.

SBGrid member Lynne Howell, senior scientist at The Hospital for Sick Children (SickKids) and a biochemistry professor at the University of Toronto, studies biofilms formed by Pseudomona aeruginosa, a bacterium that afflicts Cystic Fibrosis (CF) patients by forming biofilms inside their lungs. She recently uncovered the structure of AlgK, an outer-membrane lipoprotein on P. aeruginosa that helps the bacteria …

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Side-Track to Success

Ning Zheng

University of Washington

Published May 13, 2011

When Ning Zheng got side-tracked from his studies of protein degradation, he never expected to end up in the plant world. Today, Zheng, associate professor of pharmacology at the University of Washington and an HHMI investigator, runs a triplicate of research agendas, all rooted in Xray Crystallography, and all aiming to find new therapeutic drugs for human diseases.

Zheng started his career solving large protein-protein complexes of ubiquitin ligases and the proteins they bind with to degrade them. Malfunctions in this process of ubiquitination are involved in several diseases including cancers, neurological disorders and viral infections. …

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