When Ryohei Yasuda came to the United States in 2000 to take a postdoctoral appointment at Cold Spring Harbor Laboratory, he had to leave his harpsichord behind in his native Japan. An accomplished musician, Yasuda vowed that if he ever got a faculty position, one of the first things he was going to do was buy another. In 2005, Duke University made that offer, Yasuda accepted, and the new harpsichord was not far behind.
Even before his appointment at Duke, the biophysicist was known not for his music but for his filmmaking ability. His movies, created with the goal of understanding learning and memory, show the biological world at the molecular level.
As a graduate student at Keio University in the late 1990s, Yasuda showed that the enzyme F1-ATPase, which produces ATP, the molecule that provides cells with energy, is actually a single-molecule rotary motor. He imaged the action with a powerful microscope, capturing one of only two known rotary engines in biology; the other powers bacterial flagella. He also confirmed that the molecule is 100 percent thermodynamically efficient.
At Cold Spring Harbor Laboratory, he built a sensitive fluorescence imaging microscope to capture what is known as fluorescence resonance energy transfer (FRET)—the transfer of energy from one fluorescent molecule to another. Measuring the FRET phenomenon enabled him to see structural changes in proteins and interactions between them. More recently, at Duke, he developed a number of fluorescent indicator molecules that allow him to image protein dynamics in synapses—regions where nerve impulses are transmitted and received.
His goal is to better understand how nerve cells communicate and develop, the processes that underlie learning and memory. In particular, he is interested in synaptic plasticity—the ability of the connection between two nerve cells to strengthen or weaken.
"The list of proteins involved in synaptic plasticity grows and grows," Yasuda says. "We're trying to understand when they're activated, where they're activated, and how they play roles in synaptic strength."
His playing field is the dendrite side of nerve cells, where a neuron receives signaling information via "dendritic spines," tiny mushroom-shaped protrusions from the surface of dendrites. These spines act as gathering sites for the hundreds of proteins that form the receiving side of a synapse. Discoveries in the dendritic spine zone could someday lead to drugs for mental illnesses or for maladies such as stroke.
Yasuda has imaged the interactions of molecules as they move in and out of dendritic spines. In the coming years, he says, "our program hopes to shed light on the molecular mechanisms of synaptic plasticity. We think we will provide insights into principles of the way signaling networks operate in the physical compartments of cells."
His most recent "movie" is the imaging of a key protein involved in synaptic plasticity, calcium/calmodulin-dependent kinase II.
Asked whether he entertains the idea of combining his two passions into some sort of biological music video, Yasuda says, "That's an interesting thought."