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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 Doudna ...Find out More »
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.
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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 ...
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 question evolved ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 — got in ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 ...Find out More »
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 one ...Find out More »
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 ...Find out More »
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 form ...Find out More »
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 ...Find out More »