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Biophysicist in Profile

Ragothaman M. Yennamalli

Ragothaman M. Yennamalli

March 2024 // 1582

Ragothaman M. Yennamalli grew up in Madras, now called Chennai, in India. His father was an army accounts officer, so the family moved around often in Yennamalli’s youth. “My childhood experiences involved lots of traveling and settling in new places. An advantage of this exposure was that geog­raphy for me was never a limitation. I could adapt to new environments easily. Also, I made new friends everywhere we went,” he says. “During our years in the Andaman and Nicobar Islands, I was exposed to the diverse and wild fauna and flora these islands had. The green geckos and a unique antiseptic plant are unique to these islands. Trying to identify the wild ones, looking at coral reefs, and cohabiting with snakes and centipedes made me curious about biology, in general.”

His family is made up of artists and educators. Before his army position, his father had been a teacher for years; his mother worked as a primary school teacher. “Three genera­tions of painters left an indelible mark on me, right from my grandfather, my mom, to my brother, who are full-fledged artists. Our dinner table conversations would be mostly about art, music, dance, and K. L. Saigal songs,” he recalls. “My par­ents did not pressure me into becoming something specific. They gave full freedom to my brother and me in choosing our own paths. That privilege of choice was hugely important for me.”

After high school, he studied microbiology at the University of Madras, then went on to earn a master’s degree in micro­biology from Madurai Kamaraj University (MKU). Following his master’s studies, he studied bioinformatics at Jawaharlal Nehru University (JNU), eventually earning his PhD. “The science discussions in MKU and JNU over coffee and tea at the canteen opened my mind unlike elsewhere,” Yennamalli says. “During my master's, we had a course on structural biology and those pretty pictures of proteins fascinated me a lot! In my PhD I had decided that I would work on something related to protein structures. I learned during my coursework that computational structural biology had topics on crystal­lization and space groups. It was very fascinating to me and opened a new world to me. At that time, a new collaboration was started between JNU and the University of Queensland in Brisbane, Australia. I was nominated and I ended up studying protein structures at Bostjan Kobe and Paul Young’s lab, spe­cifically about the envelope protein of dengue virus. Dengue viral fever is endemic to both India and Australia. I took that as a PhD project and worked towards finding a drug that could help millions back home. I studied how the E protein undergoes conformational change using molecular dynamics simulations. Also, using a structure-based drug design ap­proach we identified a promising lead compound that worked in experimental setup. The guidance I received from Naidu Subbarao as a supervisor was invaluable.”

He next undertook a postdoctoral position with Alok Bhat­tacharya at JNU working on drug-resistant Mycobacterium tuberculosis genomes. Then he moved to Iowa State Universi­ty (ISU) to work with Taner Z. Sen on a carbohydrate-degrading enzyme called endoglucanase. “While my work was compu­tational in nature, I collaborated with experimentalists, and I was involved in multiple projects. This helped me acquire many different technical skills in the domains of systems bi­ology and machine learning,” Yennamalli explains. “To enhance my experience and to work in a large team, I worked with George N. Phillips, Jr. at the University of Wisconsin–Madison. I was involved with a multi-institutional structural genomics project on natural product biosynthetic pathway proteins… Later, George moved to Rice University, and I moved as well to set up the computational part of his lab and continued the same project.”

Yennamalli is now an assistant professor at SASTRA Deemed University, a primarily undergraduate institution in the south of India. His position is equal parts teaching and research. Currently, he is studying the structure and function of redox enzymes called lytic polysaccharide monooxygenases (LP­MOs) that have an unusual flat surface as part of their active site. “I am using machine learning algorithms to classify these LPMOs into various families,” he reveals. “I also work closely with my collaborator Richa Priyadarshini at Shiv Nadar University on an arsenic-resistant bacterium isolated in the fresh waters of India. We look at pathways and molecular mechanisms of how these bacteria tolerate arsenic and other heavy metals. Additionally, I have restarted working on ge­nomes, especially on indigenous bovine genomes, to under­stand their genetic makeup for climate resilience and disease resistance.” He also works on small projects with his under­graduate students, led by the students’ interests. These side projects often end up being quite exciting and rewarding. “One of these side gigs was on the calcium-dependent conforma­tional changes in the human transglutaminase 2,” Yennamalli says. “This was the work that I presented as a poster at the 2024 BPS Annual Meeting. As clichéd as it sounds, mento­ring is the most rewarding aspect of this gig. As I work with undergraduate students, when I explain and teach certain higher abstract concepts, the moment the light bulb goes on brings a smile to my face. It also helps that they are young, and one can mold their minds and channel their energies into something tangible.”

The biggest challenge thus far in his career has been finding community in science. “During my postdoc, I couldn’t find many postdocs who worked in the same department or in the same building. It made me go out of my way to find a postdoc colleague to discuss science with,” he shares. “Fortunately, there was a critical mass of postdocs at ISU and we ended up creating a postdoc association.” After becoming a faculty member, the same problem resurfaced and he realized how isolated being a principal investigator (PI) can make you feel. He struggled at first, before finding new ways to connect with his peers. “After a lonely period of three years, I found my people in the NewPI Slack and that changed my life for the better,” he says. “Now, I am blessed with colleagues in India with whom I can discuss science and we help each other out professionally. Finding other Indian PIs over X [formerly Twit­ter] has been a life-changing experience.”

The Biophysical Society has been another source of connec­tion for Yennamalli. “BPS is very inclusive and welcoming. Without question, the Annual Meetings are the best,” he says. “After every BPS meeting, I come back supercharged and bursting with ideas and thoughts that sustain me for a long time. I have benefited both personally and professionally from my membership in BPS. Personally, I made a lot of friends at BPS meetings; professionally I benefited when I started giving back by participating in committees.” His postdoc PI recom­mended he get involved with the Society’s Public Affairs Com­mittee. He tells us, “It was intimidating at the beginning but after a few meetings, I was at ease and started vocalizing my views. After two terms, I got involved with the Early Careers Committee. My two terms were so rewarding to me. These committees are special and highly useful.”

Yennamalli spends much of his time teaching budding scientists, and the advice he shares with those just starting study and careers in biophysics is some that he was given by biophysicist Rajini Rao of the Johns Hopkins School of Medi­cine. That advice includes: Prepare yourself at every step; be it classes, grants, or meetings, planning and preparing takes you far. Communicating what you think and what you want is key to getting people to listen to you. Find your support system and stick with them! Of course, family is the most important support, but next are your friends and colleagues. Do not compare yourself with others; compare you to yourself from the past; look at where you are now and how far you have come. Take calculated risks in science; challenge your­self to learn new things and expect a fair amount of failure. It is a marathon and not a sprint; so, listen to your gut instinct and take breaks from the grind; you’ll need lots of energy and motivation to keep going.