Dr. Debabrata Das’s interview with Bio Patrika hosting “Vigyan Patrika”, a series of author interviews. Dr. Das completed his Ph.D. as a DST-INSPIRE fellow in the Cellular and Molecular Endocrinology Laboratory of Dr. Sudipta Maitra at the Department of Zoology, Visva-Bharati University, Santiniketan, India. His Ph.D. work focused on the role of the insulin-signaling pathway in regulating female reproduction using zebrafish as a model organism.
After his Ph.D., he joined the Arur Laboratory at the University of Texas MD Anderson Cancer Center in 2017. He is currently an Odyssey Postdoctoral Fellow. Using C. elegans germline, his research investigates downstream substrates of the RAS/ERK signaling pathway in female fertility regulation, especially meiosis I, and their role in cancer progression.
Here, Debabrata discusses his PhD work titled: “ERK phosphorylates chromosomal axis component HORMA domain protein HTP-1 to regulate oocyte numbers”,
Published as first author in Science Advances (2020).
Author interview
How would you explain your paper’s key results to the non-scientific community?
The birth of a healthy baby requires an egg and a sperm to fuse. In women, eggs (oocytes) are formed while still in the womb and remain fixed in number. A low number of eggs can lead to infertility or premature menopause.
To study what regulates egg numbers, we used Caenorhabditis elegans—a small worm model where eggs are produced continuously in adulthood, making it easier and ethical to study.
Our lab previously discovered that the RAS/ERK signaling pathway controls egg numbers. An increase in RAS or a decrease in ERK affects how many eggs are produced. I joined the lab curious to understand how this signaling circuit controls egg formation.
In my work, I discovered a new protein called HTP-1, which interacts with the RAS/ERK pathway. ERK adds a phosphate group to HTP-1. This phosphorylated form of HTP-1 signals the cell to proceed in forming an egg. Without this modification, the cells don’t proceed to form oocytes.
So, phosphorylated HTP-1 acts like a timer, telling the cell it’s ready to become an egg. This mechanism plays a crucial role in female fertility.
This study also links female fertility with maternal nutrition. Our lab previously found that nutrition regulates the RAS/ERK pathway. Without food, ERK is inactive, and worms do not make eggs. I added that only with good nutrition does ERK activate HTP-1, allowing egg formation.
“[…] our work reveals a direct connection between female fertility and the nutrition of the mother, and because the genetic circuitry is conserved from worms to humans […].”
What was the exciting moment (eureka moment) during your research?
Initially, I assumed the egg increase was due to either more stem cell divisions or less cell death—based on textbook knowledge. But I found no difference in either. I was stuck.
Then, I observed that in the RAS(active) mutants, oocytes formed much earlier than in normal worms. That’s when it hit me: It’s about the timing, not the number of dividing cells.
Maybe the cells are moving faster into oocyte development—not multiplying more or dying less. That night I couldn’t sleep. The next day, I showed the images to my mentor Swathi and shared my hypothesis. She was thrilled and said: “We’re onto something cool here!” The rest is history.
What do you hope to do next?
I’m still in the steep learning phase with worms. Based on this work, we identified another protein, HTP-3, as an ERK substrate, and I’m following up on that.
I’m also exploring how a dual-specificity phosphatase (DUSP) influences ERK activation and meiosis in the C. elegans germline.
It’s an exciting time with multiple projects ahead!
Where do you seek scientific inspiration?
I love reading scientific biographies and discovery stories—they truly inspire me. My Ph.D. guide Prof. Sudipta Maitra and current mentor Prof. Swathi Arur have both deeply influenced my scientific path.
Also, discussions with colleagues and my wife (a microbiologist) spark ideas. And nothing beats the thrill of seeing something new under the microscope—knowing you’re the first person in the world to see it!
How do you intend to help Indian science improve?
Though I’m still learning, I plan to return to India and run my own lab. I realized my love for science during school years, so I’d love to visit schools and engage students with science talks and simple biology experiments.
If we nurture curiosity early, we can inspire the next generation of scientists.
Reference
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Das, D., Chen, S.-Y., Arur, S. (2020).
ERK phosphorylates chromosomal axis component HORMA domain protein HTP-1 to regulate oocyte numbers. Science Advances, 6(44): eabc5580. -
Lee, M.-H. et al. (2007). Genetics, 177: 2039–2062.
Multiple functions and dynamic activation of MPK-1 in C. elegans germline development. -
Lopez III, A.L. et al. (2013). Developmental Cell, 27: 227–240.
DAF-2 and ERK couple nutrient availability to meiotic progression in C. elegans.
Edited by: Govinda Raju Yedida (Volunteer, Bio Patrika)
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