Ajit Prakash is a postdoctoral researcher in biochemist Sharon Campbell’s group at the University of North Carolina at Chapel Hill. He studies G-protein signaling, protein dynamics, and biophysical mechanisms underlying cellular regulation, with implications for signaling-related disease biology. In this Postdoc Portrait interview, he shares how persistence and curiosity can give new life to core concepts in cell signaling.
Visualizing Molecular Dynamics with NMR Spectroscopy
Q | What drew you to G proteins and cell signaling?
My interest in science grew from a deep curiosity about how complex biological behavior emerges from invisible molecular events. During my early training, I was fascinated by the idea that tiny changes in protein structure or interactions could have dramatic consequences for cellular function and disease. This curiosity led me to pursue biochemistry, where I could ask detailed mechanistic questions.
During my PhD, I worked on FK506-binding protein 3 (FKBP25), a nuclear immunophilin involved in protein-nucleic acid interactions. Studying FKBP25 introduced me to the power of structural and biophysical approaches, particularly nuclear magnetic resonance (NMR) spectroscopy, to understand how proteins recognize partners and regulate cellular processes. That experience shaped how I think about biology—not as static pathways, but as dynamic, adaptable systems.
This perspective naturally drew me to cell signaling and G proteins, which sit at the heart of cellular communication. What continues to motivate me is the opportunity to uncover unexpected regulatory mechanisms and translate molecular insight into a broader understanding of how cells function in health and disease.
Q | What scientific problem are you trying to solve?
My favorite research project explores how cells sense and respond to subtle changes in their internal environment, particularly intracellular pH, through core signaling proteins. In our recent work, we discovered that Gαi—a well-known G protein involved in G protein-coupled receptor signaling—also functions as a molecular pH sensor. This project excites me because it challenges a long-standing view of G proteins as passive signal relays and instead reveals them as active interpreters of cellular conditions.
What fascinates me most is the molecular elegance of the system. Small shifts in proton concentration lead to coordinated changes in protein dynamics, nucleotide cycling, and signaling output. Using a combination of NMR spectroscopy, protein engineering, and functional assays, we were able to pinpoint specific charged residues that govern this pH sensitivity. Identifying these residues after many rounds of trial and error was deeply rewarding.
Beyond the basic science, this project has broad implications. Altered intracellular pH is a hallmark of diseases, such as cancer, and understanding how signaling pathways adapt to these changes could open new avenues for therapeutic intervention. It’s a project that sits at the intersection of fundamental biology and real-world impact.
Decoding G-Protein Signaling and pH Regulation
Q | What has been the most rewarding part of your research journey?
The most exciting part of my scientific journey has been realizing that persistence and curiosity can fundamentally change how we understand biology. Throughout my career, I’ve been drawn to questions that sit just outside conventional thinking—questions that initially seem subtle or even unimportant. My work on Gαi as an intracellular pH sensor is a perfect example. What began as a simple curiosity about pH effects evolved into a discovery that reframed a core concept in cell signaling.
A defining moment came when, after extensive trial and error, we identified three key residues that completely controlled pH sensing. Mutating those residues eliminated the effect entirely. That “aha” moment—when messy data suddenly forms a clear story—is what keeps me passionate about science.
Equally exciting has been the collaborative nature of the journey. Working with mentors, colleagues, and trainees across disciplines has shaped not only my scientific thinking but also my approach to mentorship and leadership. Seeing our work recognized through publication and media coverage reinforced the idea that careful, curiosity-driven science can resonate far beyond the lab.
Q | If you could be a laboratory instrument, which one would you be and why?
I would be an NMR spectrometer. NMR doesn’t just provide static snapshots; it captures motion, flexibility, and dynamics—the subtle behaviors that often determine how biological molecules truly function. That perspective resonates deeply with how I think about both science and life.
Much like NMR, I’m drawn to complexity beneath the surface. I enjoy digging into problems that don’t have immediate or obvious answers and extracting meaningful patterns from noisy data. NMR also rewards patience and precision—qualities that are essential in research and that I’ve learned to value over time. Experiments can take days or weeks, but when they work, they reveal insights that no other technique can.
On a lighter note, NMR instruments are often tucked away in quiet rooms, steadily working behind the scenes, yet they play a central role in many discoveries. I like that idea—contributing deeply and consistently, even if the impact isn’t always immediately visible. In many ways, that’s how I see my role as a scientist.
Responses have been edited for length and clarity.
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