Dr. Cohen is also a professor of chemistry and chemical biology and of physics at Harvard University.
Developing New Physical Tools to Study Molecules and Cells
As a kid, Adam Cohen used to bring home junked TVs, computers, and other electronic gear and tear them apart to find out how they worked. He used what he learned to build his own devices. "I basically set up my bedroom as an electronics shop," he recalls. Before high school was over, he'd constructed a scanning tunneling microscope. He liked the idea of resolving individual atoms and being able to move them around, which this scope could do. It earned him first place in the 1997 Westinghouse Science Talent Search. He had seen one of the microscopes while visiting a lab at Princeton University and thought, "Wow, it would be fun if I could build one."
That passion to create cool stuff still motivates Cohen, who is now at Harvard University. "We develop new physical tools for studying how cells, molecules, and even whole organisms work," he says.
To prepare himself for this work, Cohen earned two PhD degrees. The first, from Cambridge University in the United Kingdom, was in theoretical physics. But the PhD program lasted only two years—not long enough, according to Cohen. "I felt that I didn't have enough training and experience to go do a postdoc." So he began a second PhD program at Stanford University, where he focused on the biophysics of single molecules. Researchers have long wanted to follow individual molecules in a solution and monitor their movements and interactions, Cohen says. "The challenge is that they don't hold still. In solution they jiggle around like crazy due to Brownian motion." So he devised a machine that tracks individual molecules with lasers and then briefly immobilizes them with an electric field. During his PhD research he was able to detain complexes of multiple proteins and large strands of DNA, and in his lab at Harvard, he showed that the method could restrain even small proteins or single dye molecules.
But his failure to get the technique to work for one kind of molecule led to what he describes as his most significant discovery so far. Cohen and colleagues were attempting to apply the method to microbial rhodopsins, a family of light-absorbing proteins. Single-celled microorganisms called archae living in the Dead Sea use this form of rhodopsin like a personal photovoltaic cell to convert sunlight into electricity. After two years of trying, his team wasn't able to trap rhodopsin molecules. "We wanted to find something else to do with them," Cohen says. Some rhodopsins capture light and use the energy to modify the voltage across the cell membrane. "Our hypothesis going in was that we might be able to run this protein in reverse," Cohen says. "So instead of taking in light and generating electricity, we could use it to sense electrical energy in a cell and convert that into a detectable optical signal." Maybe the rejiggered proteins would be useful for monitoring the electrical activity of cells.
Cohen and his team reengineered one type of rhodopsin to modulate its fluorescence in response to the voltage across a microbe's membrane. When the researchers inserted the altered molecule into Escherichia coli bacteria, the microbes occasionally flashed, suggesting they were continually adjusting the voltage across their membrane, possibly to allow the import or export of certain molecules. "This was a huge surprise," Cohen says.
Even better, when they inserted a different reengineered rhodopsin into rat neurons growing in a lab dish, the rat neurons that carried the altered rhodopsin lit up when they fired off an action potential, or electrical impulse. Researchers can track the activity of neurons using electrodes, but they've long hoped to observe this electrical activity, so far without much success. The technique could bring this dream closer.
Cohen's team is tinkering with the molecule to make it faster, brighter, and less disruptive to the cell. "We've made great headway in improving it," he says. They are also collaborating with other scientists to slip the protein into the neurons of rats, so they can monitor neuron firing in living animals. Other possible applications for the technique range from discovering how electrically active organs such as the brain and heart "boot up" during development to understanding the defects behind long QT syndrome, a condition that leads to erratic heartbeat. "There's a whole world of things to explore," Cohen says.