Biophysical Society Bulletin | October 2022

Biophysicist in Profile

Swetha Murthy Area of Research Gating and function of mechanosensitive ion channels

Institution Vollum Institute, Oregon Health & Science University

At-a-Glance

Swetha Murthy has been fascinated by science since she was a young child, and her curiosity and hard work have carried her to her current position as an assistant professor at the Vollum Institute at the Oregon Health & Science University.

Swetha Murthy

Swetha Murthy , assistant professor at the Vollum Institute at the Oregon Health & Science University, grew up in South ern India. When she was a child, her father was in the Indian Navy, so the family moved around frequently before settling in Bangalore during her high school years. Her parents, an engineer and a teacher, encouraged curiosity and learning. “I grew up in a household where reasoning and questioning processes and ‘how things work’ was encouraged. This really instilled inquisitiveness in me and nurtured my enthusiasm for science,” she shares. She attended Bangalore University for her undergraduate studies and her master’s degree, and then moved to the Unit ed States to pursue her PhD at the State University of New York, Buffalo. “My interest in biophysics piqued when I was a graduate student in Gabriela Popescu ’s lab, where I studied gating kinetics of NMDA receptors. I really enjoyed immersing myself in the molecular mechanisms of ion channel function.” Following completion of her PhD, Murthy undertook a postdoctoral position at Scripps Research in La Jolla, Califor nia. She was eager to expand her research experience and make an impact on the ion channel field, and landed in Ardem Patapoutian ’s lab. “The lab had just discovered the first bona fide eukaryotic mechanosensitive ion channel PIEZOs, and to me that seemed like a budding topic, especially from the perspective of biophysics. There was so much unknown with these fascinating channels. His lab is also where I fell in love with somatosensation and, although my training was not in neuroscience, I learned to include a broader perspective to my training in molecular function and biophysics of ion channels,” she continues. “I joined Ardem’s lab just a couple years after PIEZOs were discovered and witnessed firsthand all the PIEZO-related discoveries that his lab subsequently made, which led to [Patapoutian’s] Nobel prize. This was truly inspirational and motivating.”

“I studied biophysical properties as well as in vivo function of the mechanosensitive ion channel PIEZOs. My work eluci dated a lot of the initial biophysical properties and molecular determinants of the channel that are important for the pore and gating,” Murthy explains. “But probably my most inter esting contribution to science was determining that PIEZO2 is the sensor for tactile allodynia, a phenomenon when touch evokes pain during conditions like sun burn, fibromyalgia, or after inflammation or injury. This was a surprising result because the common theory was that although touch was dependent on PIEZO2, inflammation- or injury-mediated mechanical pain was probably transduced by other mechan ically activated ion channels. Also, these results allow us to target topical drugs to inhibit PIEZO2 as a means to manage pain caused from tactile allodynia.” Murthy is now an assistant professor at the Vollum Institute, part of Oregon Health & Science University. Her lab studies the mechanosensitive ion channel family OSCA/TMEM63, how these channels are gated by force, and their underlying function in mammalian physiology. “OSCAs—which is the gene name for the ion channels present in plants—are a large family of 15 genes. The different isoforms have un paralleled diversity in mechanosensitivity and biophysical properties,” she reports. “This is in contrast to other MA ion channel families, which have only one or two members, with largely comparable biophysical and structural properties that have hindered the identification of distinct gating domains. Therefore, the lab is currently using OSCA channels as a tool to mine information about molecular mechanosensation. Our efforts will provide deeper insights into gating of these channels.” The biggest challenge in her career thus far came after the early success she found during her postdoctoral training. “I longed for a physiological perspective, and hence, I took up

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