Sound waves, wind on skin, blood moving through vessels – these are all force-inducing stimuli that initiate a cascade of events leading to a person’s ability to hear, sense touch or regulate blood pressure.
Above: Swetha Murthy, Ph.D., in her lab at OHSU’s Vollum Institute. (OHSU/Christine Torres Hicks) Swetha Murthy, Ph.D., assistant scientist at the Vollum Institute, explores the physiology of mechanotransduction, or the conversion of mechanical force into biological signals. To advance these investigations, Murthy is developing leading-edge tools to discover the molecular basis of touch and hearing. She joined the Vollum Institute in 2019. We sat down with her to talk about her work.
Tell us about your background and how you came to your research
My upbringing definitely facilitated my trajectory, where science was given a lot of importance and critical thinking and developing new ideas were always encouraged. So, definitely in that sense, my family played a very strong role in my passion for science. My parents also encouraged me and gave me complete freedom to do what I wanted to do. Going to the State University of New York in Buffalo after my masters at Bangalore University, in India, was a very positive move.
I fell in love with biophysics and physiology in the lab of Gabriela Popescu, at SUNY-Buffalo, where I studied gating mechanism of NMDA receptors that are present in specific areas of the brain and are required for learning and memory. My goal there was to understand how these NMDA receptors function, particularly their gating mechanism. How does this receptor transition to different states that allow it to function?
After finishing my doctorate, I went to the Patapoutian Lab. At that time, in 2010, his team had just identified the first eukaryotic mechanosensitive ion channels, PIEZOs, that were later shown to be required for a sensation of touch. These channels are not only required for a sense of touch and proprioception in mice and humans, but there are so many other underappreciated processes that depend on these channels. For example, they are required for vascular development and red blood cell volume regulation. At that point, we didn’t know how big a deal that discovery was. Now we do — he won the 2021 Nobel Prize in Medicine and Physiology for discovering these receptors.
These are mechanically activated ion channels, which meant that physical force or physical stimulus, such as our sense of touch, can initiate or activate them. However, their molecular nature was unknown until the Patapoutian Lab made their discovery in 2010. The amount of growth and scientific knowledge that I acquired in the Patapoutian Lab was immeasurable — it was very much a case of being in the right place at the right time.
Tell us about your current research
What my lab aims to accomplish in the next five to six years is to better understand how this other family of mechanosensitive ion channels called OSCA/TMEM63 function and what their role is. As I got to know more about the field, I realized there are still quite a few hard-hitting unanswered questions, and that is fascinating and challenging.
Among other projects in the lab, I intend to use light-activated lipids to apply mechanical stress on the membrane and open the channel, enabling researchers to activate them with more precision and capture them in different conformations.
My hope would be to develop and apply this new technique to gain a better perspective on how these channels function at a cellular level,” she said. “That will then open the way to developing drugs that could selectively block the channel.
What do you do when you’re not working?
I love to hike and backpack. And, the Pacific Northwest is amazing for that.
In October 2021, Murthy earned the New Innovator Award from the National Institutes of Health. The award provides $1.5 million over five years to support early-career investigators involved in high-risk, high-reward lines of research. This work is supported by grant award R01MD017405, funded by the NIH Common Fund.
Also in 2021, Murthy was one of two visionary OHSU researchers to receive a $750,000 award through the OHSU Faculty Excellence and Innovation Award program generously supported by the Silver Family.
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