Cell migration is a fundamental process that plays a crucial role in a wide array of physiological and developmental scenarios, such as immune response, wound healing, stem cell homing and embryogenesis. On the other hand, its dysregulation often results in different detrimental outcomes, including autoimmune diseases, cognitive deficits and cancer metastasis. As an upshot of extensive research for the past three decades, many signal transduction and cytoskeletal molecules have been identified that collectively work to sense and process different external cues, generate proper polarity and help the cell to correctly navigate via coordinated protrusions and contractions. While numerous specific interactions among many such signaling and cytoskeletal molecules have been deduced through biochemical and genetic analyses, how the activities of so many different components are spatially and temporally coordinated at the subcellular scale has remained unclear. In other words, little was known about the global scale organization mechanisms that determine when and where the next protrusions will form or how polarity will be organized in a migrating cell.
My research, carried out in the labs of Peter N. Devreotes and Pablo A. Iglesias, answered these fundamental questions on cell migration and signal transduction. We demonstrated that the dynamic regulation of inner membrane surface potential is sufficient and necessary to regulate the cell polarity and migration mode. We developed novel monitoring tools and optogenetic actuators that can work in conjunction with standard live- cell imaging setup and genetic/pharmacological perturbations. Using these systems, we established that surface charge on the inner leaflet of the plasma membrane, a biophysical property — not some coincidental congruence of stepwise specific biomolecular interactions — spatially and temporally orchestrate signal transduction activities in the cell to control protrusion formation. Our experiments in Dictyostelium amoeba and different mammalian cells demonstrated that surface charge is dynamically altered during signaling network activation and, in turn, its generic perturbation can induce or inhibit signaling activities that mediate cell migration. It is well known that during propagation of nerve impulse, transmembrane potential can regulate the opening of the specific ion channels, which in turn collectively define the transmembrane potential. Our results indicated that transiently lowered inner membrane surface potential, which we termed “action surface potential,” can analogously propagate and interact with signaling network activation.
Questions & Answers
Why did you choose Johns Hopkins for your work?
I was excited to join Johns Hopkins because it is one of the world’s premier biomedical research institutions. Hopkins has cutting-edge research facilities and perhaps more importantly, a close-knit intellectual community, where many of the members are pioneers in their respective research fields.
Moreover, I believe the Hopkins ecosystem has a sincere appreciation for the fundamental biomedical research that is curiosity-driven and simply tries to understand the basic rules of life, but often has an incidental impact in developing advanced therapeutics. Overall, Johns Hopkins offers a unique conducive environment to pursue novel ideas in basic sciences. And, I think Baltimore is cool!
What does receiving this award mean to you personally and professionally? Do you have any connection with the particular award you received?
I am honored and humbled to receive the David Israel Macht Research Award. I have found that many of the previous awardees went on to have illustrious research careers, and I feel truly privileged to join that exceptional list of Ph.D., M.D, and M.D.–Ph.D. students. Dr. Macht helped establish multiple new biomedical research domains, and I am excited to follow in his footsteps.
What contributed to your project’s success?
It is a real privilege to work in Devreotes’ and Iglesias’ labs. Peter’s and Pablo’s sagacious guidance in experimental and computational science, respectively, was one of the biggest reasons for the project’s success. They offered ample scientific freedom to pursue new ideas while providing unwavering support when difficulties were encountered. All the lab members deserve special thanks as well for their constructive criticisms. I also think that my previous training in engineering has helped me to think from a different perspective and form new hypotheses. My thesis review committee members, Konstantinos Konstantopoulos and Shigeki Watanabe, have always asked the right questions and provided substantial guidance. Several other faculty members, especially Douglas Robinson, Miho Iijima, Deborah Andrew and Chuan-Hsiang Huang, also generously provided valuable input. And, of course, my co-authors were amazing, and working with them was really exciting!
What thoughts do you have about Young Investigators’ Day itself, as a celebration of the roles student and fellows play in research at Johns Hopkins?
Young Investigators’ Day is a fantastic platform that provides tremendous encouragement to graduate students and postdoctoral fellows. Research is often difficult, and hence, recognition always helps! During my time here, I have looked up to many previous Young Investigators’ Day award winners, and it feels great to join that cohort. Also, I think the presentations and poster sessions during the event provide wonderful opportunities to discuss science with Hopkins community members from broadly varied research and clinical backgrounds.
What has been your best/most memorable experience while at Johns Hopkins?
It is always fascinating to see experiments actually work after hours of planning, preparation and troubleshooting! Other than that, I vividly remember that I was really excited when I first got the opportunity to join Devreotes’ and Iglesias’ labs. That was one of my most memorable moments. Additionally, I will always cherish the discussions I regularly had with my lab mates, who came up with fresh viewpoints — on numerous topics, ranging from science to politics, and everything in between!
What are your plans over the next year or so?
I am planning to graduate within a few months and then continue to work in basic biomedical research domains, while fostering a diverse and inclusive environment.
Tell me something interesting about yourself that makes you unique. Do you have any special hobbies, interests or life experiences?
When I was in school, I was a recitation/elocution artist and a theater actor— I performed in many major auditoriums in our state. Right now, when I have free time, I listen to different types of hip-hop music, read the history of India (and the world), and tinker with my Linux servers and desktops. I also love to watch cricket and soccer. And, last but not least, I sometimes just love to take a quick (or long) nap!