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Biophysicist in Profile

Harpreet Singh

Harpreet Singh

December 2022 // 2962

Harpreet Singh was born in a village called Odhra, near Dasuya, Punjab, India. His father served in the Indian army, so the family moved around India in Singh’s early years. At 11 years of age, he entered a military boarding school in Chail, Shimla. It was there that he first became interested in science. “The majority of my schooling was done in the Military School, India,” he shares. “My science teachers in the school were the best ones as they encouraged us to think beyond textbooks and challenged us with problems that encouraged us to think.”

Singh attended St. Joseph’s College in Bangalore, India for his undergraduate studies. “During my college years, I got an opportunity to work with my zoology professors to carry out small research projects, which earned me publications on butterflies as well as human genetics. Eventually, I was a summer intern in M. K. Mathew’s lab at the National Centre for Biological Sciences, Bangalore, where I was introduced to ion channels. The group was working on potassium channels, and it was amazing to observe currents being recorded from Xenopus oocytes,” he explains. “That is where my interest in ion channels developed. I was fascinated by electrophysiology and the idea of currents being measured from living cells. I continued my journey into ion channel biophysics at Edin­burgh University Medical School where I did my PhD under the mentorship of Drs. Richard Ashley and Michael Cousin.”

As he was completing his PhD, Singh began looking for an opportunity to visualize functional ion channels at nanoscales. He undertook a postdoctoral position with Ligia Toro and En­rico Stefani at the University of California, Los Angeles. “With Drs. Toro and Stefani, I established the molecular identity of a mitochondrial BK channel and visualized it with a ‘homemade’ [stimulated emission depletion] microscope,” Singh says. “We also discovered that activation of the BK channel can protect the heart from ischemia-reperfusion injury.”

“There was a time when I almost gave up my postdoctoral training, but thanks to Profs. Toro and Stefani who encour­aged and supported me, I was able to give myself a second chance. My PhD mentors, Profs. Ashley and Cousin from Edin­burgh, kept my morale high, and Prof. Robert Chow from [the University of Southern California] went out of his way to offer me help and guidance. I have had a strong and exceptional mentorship team that believes in my science,” he reveals. “I still remember Prof. Jianmin Cui from Washington University walking up to my poster at the Biophysical Society meeting and encouraging me to apply for faculty positions within the USA, and that was the time I really believed I had a chance at being faculty.”

Singh is now an associate professor in the Department of Physiology and Cell Biology at The Ohio State University College of Medicine. “Our group focuses on newly discovered intracellular K and Cl channels in cellular organelles such as exosomes and mitochondrial membranes. We also study their role in heart failure and heart function,” he explains. “We explore the basic biophysical properties of intracellular ion channels using a combination of planar bilayers, patch clamp, near-field electrophysiology, and multi-electrode arrays. We interpret the distribution of proteins by high- and super-reso­lution microscopy, and for physiology, we use optical coher­ence tomography, echocardiography, and cell-based assays.”

“I am extremely fascinated by ion channels and how they function. It is exciting to see how these channels maintain selectivity and open and close under different circumstances, especially in disease scenarios. I always tell my undergradu­ate physiology students that ion channels are faster than you think,” says Singh.

He finds the challenge of the work and the joy of discovery to be deeply rewarding aspects of his career. “Every single day is a new challenge, and it ends with new knowledge. The ex­citement associated with every single trace obtained from ion channels embedded in organellar membranes is just amusing enough to keep me awake at night,” he goes on. “Traveling around the globe to present and meet new and old friends is also highly rewarding. Recently, a mother of an 11-year-old child contacted me as her son had a mutation in one of the proteins I had worked on. That was a moment that made me feel everything I do is worth it, and we can make a difference.”

“My future plans revolve around the characterization of novel ion channels we have discovered and the push towards drug discovery. We have identified patients with mutations in these channels, and the real challenge is to find therapeutic interventions for the novel ion channels we are working on,” he explains.

Singh has attended the BPS Annual Meeting since graduate school and has felt the support of the biophysics community during critical moments of his career. “I was encouraged to get a faculty position when I was not even thinking about applying. I have met scientists who went beyond their obli­gations to guide and mentor me,” he says. “There were times when I was in low spirits at a critical point of my career. I met biophysicists who believed in me and my science and helped me to immediately bounce back.”

To give back to the community that has supported him, Singh serves on the Society’s Early Careers Committee, which is responsible for organizing the Career Development Center at the Annual Meeting and career development webinars throughout the year as well as writing the BPS Bulletin’s Mol­ly Cule advice column, among other activities. “I am delighted that I get a chance to make significant contributions to the biophysics community,” he declares. “I appreciate the hard work done by every single member of the committee and the support from the Society. The transparency and collegiality keep attracting new members and it is fun to work and plan with everyone.”

When asked what advice he would give to people just start­ing their careers in biophysics, Singh replied: “Biophysics is both exciting and challenging. The biophysics group across the globe is extremely friendly and collaborative. You should never be shy about reaching out, asking questions, seeking advice, and networking. The annual conference is one of the best platforms to meet lifelong friends and colleagues. Usually, you will hear that you should pick the right thing for your career. You have already picked biophysics, which is the right thing; now, just follow your passion. There are several opportunities in the field of biophysics, and the skills you gain in biophysics are transferable.”