Scripps Research Institute
Dr. Patapoutian is also a professor in the Department of Molecular and Cellular Neuroscience at The Scripps Research Institute.
Molecules of Mechanotransduction
Growing up in an Armenian family in Lebanon, Ardem Patapoutian attended the American University of Beirut, where he saw a chapter on DNA and molecular biology in his zoology textbook. "I had never heard of these and was excited to find out." But his zoology professor skipped over that material out of distaste for what he called "trendy science."
"This was the late 1980s—not the 1950s!" exclaims Patapoutian. A year later, in 1987, he left Lebanon for the United States and enrolled at the University of California, Los Angeles, where he took Bob Goldberg's molecular biology course. "I learned about Watson and Crick and Meselson and Stahl, and I was hooked," he says. Patapoutian also found he loved the culture and intellectual challenges of the research laboratory. For his studies, he searched for a problem that was very important and about which little was known.
He chose to study the scientifically mysterious sense of touch, embarking on a fruitful series of experiments to reveal its molecular basis. Touch registers tactile stimuli as well as temperature changes, transmits the effects of hot peppers and menthol shave cream, and conveys mechanical forces such as stretch in internal organs and the response of delicate hair cells to auditory signals. Touch brings us vital information, pain, and pleasure. Yet at that time—about 20 years ago—the mechanisms of touch perception were more or less a black box to neuroscientists.
Patapoutian's group at the Scripps Research Institute began by hunting for molecules involved in temperature sensation. The team identified three ion channels Patapoutian calls "molecular thermometers" within touch-sensitive cells. The first two are cold-sensing channels, TRPM8 and TRPA1, and the third is a warmth-activated channel, TRPV3. TRPM8 responds not only to cold but also to the cooling sensation created by compounds such as menthol, found in peppermint.
In addition to cold, the TRPA1 channel senses ingredients in wasabi and other noxious chemicals that elicit pain and inflammation. Because this channel works within the peripheral nervous system, Patapoutian hopes it will be possible to develop analgesics that are less addictive than opioid drugs, which act through the central nervous system.
In recent years, Patapoutian has shifted his focus from temperature to mechanical force. Mechanotransduction, the process by which cells convert mechanical forces into chemical signals, "is arguably the most important remaining question in vertebrate sensory transduction," he says. "Almost every tissue in our body experiences mechanical forces, but we realized that very little was known about how you sense these forces." A major step in understanding came in 2010 when he and postdoctoral fellow Bertrand Coste identified proteins that respond to mechanical pressure; they named those proteins Piezo1 and Piezo2 (piezi is the ancient Greek word for pressure). In 2012, they showed that the piezo proteins are ion channels, some of the largest ever discovered.
Piezos are expressed in many mechanosensitive cell types, and Patapoutian now has a long to-do list of experiments aimed at determining their role in important physiological processes—among them, how sensory neurons sense touch, how the cochlea senses sound waves, how lungs sense air pressure, and how blood vessels respond to changes in blood pressure. The Patapoutian lab is using gene-knockout techniques to find out the role of Piezos in these various physiological processes.