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Chemistry Faculty: Beratan, Derbyshire, Hargrove

When a professional journal in your field dedicates an entire issue to reviewing your life’s work, you have a unique opportunity to look back on your career.

Originally published by Trinity College of Arts & Sciences.

David Beratan Reflects on the Humans Behind the Science
 

“I can’t believe I’m as old as I am,” said David Beratan, who recently had that experience when the Journal of Physical Chemistry B published a special issue in honor of his 60th birthday. “It’s a privilege, an honor. It’s flattering and a little bit embarrassing.”

Of course, not everyone gets this treatment, however long their careers. Beratan, the R.J. Reynolds Distinguished Professor of Chemistry, has impacted his field in ways that are “both extraordinarily diverse and profound,” the issue’s guest editors wrote, including “a broad and deep impact on chemistry, biochemistry, and biophysics.”

But Beratan sees things in more personal terms. “I was struck by how human an activity science is,” he said. “Many of the choices of problems I went after were defined by the people around me.”

The Journey to Duke and Back to Duke

Born to a teacher and a professor, Beratan was interested in science from an early age. When he came to Duke as an undergraduate student in 1976, he quickly found his way into what would become his lifelong field: theoretical chemistry. He began lab work in the cutting-edge quantum chemistry of the time, as well as numerical analysis.

Later, during his doctoral training at Caltech, Beratan began focusing on electron-transfer theory—one of the topics he still works on today. He then spent five years working at NASA’s Jet Propulsion Laboratory, examining the way electron transfer works in biological systems. But the draw of teaching was great, and Beratan jumped at an opportunity to join the faculty at the University of Pittsburgh in 1992.

After 10 years of innovative teaching and research, Beratan reconnected with colleagues at Duke during his 20th college reunion. That connection turned into a faculty offer. Excited about a growing department with a renewed interest in cross-disciplinary research, Beratan rejoined his undergraduate institution.

The Function of the Form

Across all of those career stops, Beratan’s research has focused on two unifying themes, both of which center on the electron.

The first is the chemical origins of useful properties found in “reasonably complex” molecules. “I’ve always been interested in the origins of function, or what biologists might call emergent properties—in how function arises from structure,” Beratan said.

Biological electron transfer, or how electrons move through biomolecules, is one example—particularly their interactions with oxygen. Humans extract energy from electrons, taking as much as we can before getting rid of the depleted particles, Beratan explained. We breathe oxygen because it’s a strong acceptor of those discarded electrons, which attach to the oxygen molecules.

Understanding the precise mechanisms that enable those transfers may help scientists develop useful new technologies. Beratan is developing those theories by studying certain bacteria that also respire with oxygen, but which have evolved a trick to avoid dying when the molecule isn’t available. “What they do is grow little appendages that are about as big as their cells,” Beratan said. “They’re conduits for electrons to flow, and the bacterial cells will look for minerals like iron oxide to use as terminal electron acceptors instead.”

The Mystery of the Electron

The second theme in Beratan’s work is the quantum mechanical nature of matter, especially in the behavior of electrons.

“The glue that holds everything together in chemistry is the electron,” Beratan said. “But it has dual characteristics—sometimes it acts like a wave, sometimes it acts like a particle. How these effects arise from the electrons in a molecule and what causes these behaviors to manifest is at the core of chemistry.”

The wave-like characteristics are fleeting, but when they occur, it’s possible to use them to do things that seem exotic and unexpected from our daily, macroscopic experience. “We’re trying to understand if we can use them in order to modify the way chemical reactions occur,” Beratan said. For instance, leveraging the wave-like behavior may allow chemical reactions to take place at cooler temperatures, with implications in energy science and catalysis.

“Our research has enabled us to understand how, at the level of electrons and atoms, cells manipulate and use energy. It’s one of the most fundamental features of the cell. It’s understanding how the power plant of the cell works.”

Building Lasting Relationships

As fundamental and as influential as his theories have been, Beratan said they aren’t the most important element of his work. “The biggest impact we’re going to have is not by the papers we publish, but the students we train,” he said.

Beginning in Pittsburgh, Beratan has experimented with new ways of teaching physical chemistry, combining emerging technology—he began using computers in the classroom to do real-time calculations and visualizations in the early 1990s—with educational models like the “flipped classroom,” which create a more active learning environment. He has also co-taught online courses with research collaborators from around the country in an effort to offer classes on special topics that might otherwise not take place.

The emphasis on mentorship and collaboration is evident in Beratan’s approach to chemical theory, too. “I’m problem-driven,” he said. “I’m very interested in identifying the most compelling questions coming out of the experimental groups that I can address with theories.” As a result, he has created a much-needed feedback loop between theoretical developments and experimental findings. And those relationships have turned into decades-long collaborations and friendships. One example is Michael Therien, Duke’s William R. Kenan, Jr. Distinguished Professor of Chemistry and one of the guest editors of the Journal of Physical Chemistry B issue devoted to Beratan’s career. The two chemists met when Therien, then a postdoc, visited the Jet Propulsion Laboratory during Beratan’s tenure there.

Beratan’s ongoing work is continuing in the same vein. He now runs the Center for Synthesizing Quantum Coherence, a National Science Foundation–funded project, with Therien and chemists from Northwestern University, University of California – Berkeley, and the University of Illinois Urbana-Champaign. Not only does the center continue Beratan’s already influential research and deepen his collaborative relationships, but it aims to have “a broader impact on society by developing novel schemes for cross-disciplinary student training, driving innovation, enhancing science communication skills of its participants, and contributing to a diverse STEM workforce.”

After more than 30 years of that approach, it’s no wonder his colleagues honored him in print.

Fighting Malaria in the Classroom and the Lab
 

Emily Derbyshire connecting with Duke students in the lab.
Emily Derbyshire’s focus in the classroom is overcoming the fear chemistry inspires in many students.

Emily Derbyshire wants to help people—and she wants to do it at scale.

Derbyshire became a professor because she felt the university setting offered opportunities she wouldn’t get elsewhere: pursuing research on diseases that drug companies wouldn’t fund and mentoring a diverse group of future chemists to expand access to the field.

In April, the assistant professor of Chemistry was named a 2020 Camille Dreyfus Teacher-Scholar in recognition for her work on both fronts.

“I definitely felt honored and humbled,” Derbyshire said of the honor, which includes a $100,000 unrestricted research grant. “It’s distinct from some of the other recognitions, because we put a lot of time into teaching and we care a lot about our students, and there aren’t a lot of recognitions for the teaching side. That made it especially dear to me.”

Derbyshire’s focus in the classroom is overcoming the fear chemistry inspires in many students. “I try to remove any intimidation or preconceived notions about how hard it is. I think sometimes people just never had the opportunity to be taught in a way that was accessible.”

Because students enter class with a wide array of backgrounds and experiences, Derbyshire tries to make clear how much there is that she doesn’t know. “In this big world, I want to make sure they know they all have expertise that I don’t,” she said. “We’re here to share with and teach each other.”

Having taught courses that appeal to a broad audience, Derbyshire knows many of her students won’t go on to become chemists. But that’s a benefit, she said, not a drawback. “There are many other facets, beside training the scientists who will be making drugs and building new materials and optimizing more efficient energy. It’s policy. Or students talking to someone else who doesn’t know about chemistry and letting them know how important it is to all of these things in their daily lives.”

It was a related insight about what industry chemists weren’t doing that inspired Derbyshire’s current research. While she was a postdoc at the Harvard Medical School, an alarming number of people were dying from malaria across the globe. Yet profit-driven drug companies weren’t investing in malaria research—or related parasites like toxoplasma—so Derbyshire decided to utilize the resources an academic institution offered to study the disease, searching for new druggable targets that can prevent infection.

“We’re interested in understanding the path through which the parasite goes into our cells and starts restructuring the entire environment,” Derbyshire said. “What does the parasite do to the host? What does it need from us?”

To answer that question—and eventually find a way to prevent it from happening—Derbyshire focuses on what she called an “under-theorized” step in the infection process. Most research examines the way the malaria parasite infects blood cells, which is when disease symptoms begin and treatment occurs. But prior to entering blood cells, the parasite first enters the human liver. “If you can inhibit it at that stage, it’s prophylactic,” she said.

In particular, Derbyshire has found that malaria is seeking a specific protein within its human host. “There’s a human protein that the parasite turns on, transcriptionally, and then steals. If we inhibit that protein, the parasite dies,” Derbyshire said.

With the support of her Teacher-Scholar Award and other funding, Derbyshire will deepen her research into malaria in order to better understand the mechanism it uses to manipulate those proteins. But she will also explore other parasites in the same family to determine whether they all function in a related way.

“We would have an opportunity to develop a drug that will help with many parasitic diseases,” she said.

Amanda Hargrove Has a Target on Hard-to-Fight Diseases
 

An assistant professor in chemistry has been recognized by the Alfred P. Sloan Foundation for her “potential to revolutionize” the field.

Amanda Hargrove has been named a 2020 Alfred P. Sloan Research Fellow in Chemistry in honor of her success as a chemist. The fellowship acknowledges Hargrove’s work on the small-molecule targeting of RNA, which may hold the key to curing a number of hard-to-fight diseases.

“Many of the drugs in our pharmacies today are molecules that work by binding to proteins,” said Katherine Franz, chair of the Department of Chemistry. “Amanda's ambitious and innovative research program asks the deceptively simple question: What if we had small molecules that could target large molecules of RNA that do not code for proteins? What do those chemicals even look like? It has been amazing to watch her build a research team that is answering these questions and driving this field forward. Even more impressive is the way she drives innovation: her approaches to student mentoring and fostering collegial, inclusive research and learning environments are exemplary and obviously effective!”

Growing up, Hargrove loved learning and wanted a career that would benefit society, and like many young people thought this meant becoming a doctor. “I’ve always believed it is every person’s individual responsibility to use her or his gifts to make the world a better place,” she said. However, her career path took a turn the summer after her freshman year at Trinity University when she was presented with the opportunity to do chemistry research, the obvious choice over another summer working as a bookkeeper at a construction company.

“It was that summer of research after my freshman year when I realized that scientific research was about working as a team to solve really exciting and difficult problems that were going to have an impact on the world,” Hargrove said.

Having decided on a career in chemistry, Hargrove’s first inclination was to pursue a position at a primarily undergraduate institution with a focus on teaching. She admits that this initial decision was partially based on her own self-doubt and that, after graduate school at the University of Texas at Austin and postdoctoral work at Caltech, she realized that combining her love of teaching with graduate-level research was her real passion.

At that time, the ENCODE Project was producing a new body of research about the function of non-coding DNA and RNA—the 98.5 percent of the of the human genome that doesn’t produce proteins. Formerly considered “junk,” scientists had begun to realize it played an important role in disease. Hargrove had done research on molecular recognition and how small molecules interact with large biomolecules during her PhD and postdoc, so she made targeting non-coding RNA the focus of her new research-intensive career.

Amanda Hargrove, an associate professor of chemistry at Duke.
Amanda Hargrove, an associate professor of chemistry at Duke.

“In a number of metastatic cancers, for example, the single best predictors of metastasis are actually the non-coding RNAs,” Hargrove explained. “And so we need new tools to determine the structure and mechanism of action of these molecules—with the ultimate goal of developing small-molecule drugs that can modulate their function.”

Even today, Hargrove said, there are no FDA-approved, small-molecule drugs that can target RNA in this way. “The potential is staggering,” Hargrove said. “The entire genome might become targetable if the field is successful.”

Hargrove’s work approaches the fundamental questions of that problem, finding the specific properties of small molecules that could allow them to target RNA in a selective, functional way. Doing so would open the door for new treatments for some cancers, multi-drug-resistant bacteria, HIV, and picornaviruses. So far, her laboratory has discovered specific properties shared by RNA-targeting small molecules that may help narrow the search for those drugs, and they have made progress on understanding which RNA structures may be targeted.

Hargrove doesn’t yet have specific plans for the Sloan Fellowship, which offers a $75,000 award. But she notes that the funding isn’t tied to specific deliverables, like most government funding.  “You have the freedom to test novel ideas that may be far outside of the scope of existing funding,” she said, “and that can open entirely new research directions.”