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“When a new technology is developed, we can ask: What new scientific questions can we answer? What new scientific areas can we establish?”
Jesse Winter
Jesse Winter

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As a pioneer of single-molecule imaging, Peng Chen applies the technology to studying metal atoms in cells, with implications for the development of antibacterial agents.
Jesse Winter
Jesse Winter

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Chen says, “The hope is that by understanding how these bacteria can defend against copper, for instance, perhaps we will be able to figure out a way to interfere with the bacteria’s ability to do so…and we would have a new antibacterial agent.”
Jesse Winter
Jesse Winter

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Chen also applies single-molecule imaging technology to nanoscale catalysis, with potential application for sustainable energy production.
Jesse Winter
Jesse Winter

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Chen says, “I see all of my students and postdocs carrying out the research, and I tell them, ‘You are the first person who did this,’ and we watch as people follow their pursuit. That’s very gratifying.
Beatrice Jin; Jesse Winter
Beatrice Jin; Jesse Winter

Innovating with Single-Molecule Imaging

by Caitlin Hayes

In 1989, W.E. Moerner—a Cornell University graduate and current professor at Stanford University—discovered a method that allowed researchers to see single molecules for the first time. It was a breakthrough that opened doors for the development of an entirely new technique that would impact scientific research across disciplines, and one that earned Moerner, as well as fellow Cornell alumnus Eric Betzig (Howard Hughes Medical Institute), a Nobel Prize in 2014.

In science, when one door opens, other doors do not close—just the opposite—and Peng Chen, Chemistry and Chemical Biology, saw in Moerner’s technology a path forward.

“When a new technology is developed, we can ask: What new scientific questions can we answer?” says Chen. “What new scientific areas can we establish?”

Starting out as a professor at Cornell in 2005, Chen became one of the first researchers to apply the new imaging technology to his field of expertise: biological inorganic chemistry. His lab has also pioneered the single-molecule approach to look at nanoscale catalysis. Now leading both branches of research, Chen’s work has implications for sustainable energy production as well as the development of antibacterial agents.

Metals in Biology, Bacteria as Model

To master the new imaging technique, Chen chose Harvard University for a postdoctoral fellowship with Sunney Xie—another pioneer in single-molecule imaging. After his fellowship, Chen set out to combine the technology with what he’d studied as a PhD student in Edward I. Solomon’s lab at Stanford: the role of metals in biology.

Organisms need to maintain certain concentrations of metal ions, and they have mechanisms for regulating how many metal atoms come into cells and how many are kicked out or detoxified. To study these mechanisms, Chen uses bacteria as a model system. Copper is toxic to the bacteria he studies, while zinc is essential, so the bacteria’s cells know how to measure and adjust the concentrations to achieve homeostasis. The cells know how to do this—but until recently, the processes remained enigmatic to researchers.

Chen’s lab has watched this mechanism unfold in real time. He and his team are particularly interested in observing proteins called metalloregulators that act as sensors in the cell. “These proteins sense—which means bind to a metal—so they know the metal is there,” says Chen. “Once they know the metal is there, the metalloregulator goes to the DNA and turns on the expression of another protein, and that protein will carry out the subsequent action, either to bring in more metal or get rid of it.”

With funding from the National Institutes of Health, Chen’s recent studies have elucidated how the metalloregulators interact with the DNA—where it binds, how it activates transcription, and how that transcription is halted once homeostasis is achieved. They observe the process both in vitro and in living cells.

“What I find most rewarding is identifying very compelling research problems. Then by addressing or solving them, you open new research directions, a new chapter or subchapter.”

Chen is most interested in the fundamental mechanisms, but uncovering those mechanisms may have a broader impact on disease. “The hope is that by understanding how these bacteria can defend against copper, for instance, perhaps we will be able to figure out a way to interfere with the bacteria’s ability to do so,” says Chen. “The bacteria would die, and we would have a new antibacterial agent.”

Nanoscale Reactions Catalyzed for Sustainable Fuels

A year after applying the single-molecule technology to biological systems, Chen saw that he could make a difference in another area—nanocatalysis, how nanoscale materials can act as catalysts for reactions.   

“We study chemical reactions that are either driven by thermal energy, electrical potential, or light,” says Chen. “These reactions happen on the surfaces of nanoscale particles, and the surfaces act as a catalyst, speeding up the reaction kinetics.”

The single-molecule imaging approach is particularly useful and groundbreaking in this field because of the heterogeneous make-up of nanoscale particles. “Some are bigger, some smaller, and they all have different shapes,” says Chen. “If you want to know detail, you really have to look at one at a time.”

Chen’s lab began by looking at metal-based nanoscale particles, watching reactions on a single particle. Lately, his lab has focused more on nanoscale semiconductor particles, which can absorb light energy to drive reactions. “This is part of the process that converts solar energy into chemical energy,” Chen says.

One goal of using the semiconductor particles is to make advances on a stubborn problem: how to efficiently oxidize water—to split water into oxygen and hydrogen, withdrawing electrons—in order to make fuel. “If you use a semiconductor particle that absorbs light, you can use that energy to extract electrons from water. Those electrons could be used to reduce proton to hydrogen, which will be a fuel,” Chen says.

“Reducing proton to hydrogen is the easy part,” he adds. “Oxidizing water, extracting those electrons, is the hard part. That’s why we’re studying it.”

When taking a closer look at the water-splitting reaction on semiconductor particles, Chen found that even on one particle, there are many types of surface sites where the reaction occurs. “Because the surface sites differ in structure, they’ll have different properties in catalyzing the reaction,” says Chen. “So one would like to know which site is more or less active in catalyzing the reaction and where those reactions actually occur. Our research can directly address these questions, and we’ve demonstrated that one can image these chemical reactions at specific sites.”

The knowledge of these reactions could help researchers design better, more efficient devices for harnessing solar power to create more sustainable fuels.

Opening Doors to Uncharted Waters

Chen says that he ended up in chemistry because he didn’t want to prepare for an exam. He explains: When he was a high school student in China, college entrance exams determined where a student went to school and what the student studied. But Chen, based on prizes he’d won in chemistry, was preemptively offered a spot in the chemistry program at Nanjing University. He wouldn’t have to study for the dreaded exam, but without taking it, his future was pre-predetermined.  

“Gladly, I like what I do, and I’m good at what I’m doing, but it could have gone another way!” he says. One thing Chen is sure of, though, is that he would have landed in the sciences. “What I find most rewarding is identifying very compelling research problems. Then by addressing or solving them, you open new research directions, a new chapter or subchapter.”

Teaching offers additional rewards, Chen says. “I see all of my students and postdocs carrying out the research, and I tell them, ‘You are the first person who did this,’ and we watch as people follow their pursuit. That’s very gratifying.

“The goal is to open more doors,” Chen continues. “Once you get into uncharted waters, you may encounter something that you didn’t expect. That is the hope.”