First person – Nikhil More Free

Nikhil More

How would you explain the main findings of your paper in lay terms?

Different organelles communicate and coordinate their functions to maintain homeostasis, or optimal conditions, within a cell. For instance, the endoplasmic reticulum (ER) and mitochondria dynamically interact by forming direct physical contacts – ER–mitochondrial contact sites (ERMCSs) – facilitated by specific proteins that act as anchors for this interaction. These contact platforms support various functions, including maintaining cytoplasmic Ca²⁺ levels and serving as sites for autophagosome formation. In this study, we worked on P-bodies, a type of RNA–protein granule that forms when untranslated mRNAs interact with proteins, including those responsible for their degradation. We found that a subpopulation of P-bodies localises to and is regulated by ERMCSs. Disruption of ERMCSs, which happens in many disease conditions, increases cytoplasmic Ca²⁺ levels, which in turn activates autophagy, a process that maintains homeostasis by removing unwanted cellular components. This led to an autophagy-dependent decrease in P-body abundance. Thus, our work revealed a mechanism by which ERMCSs regulate P-bodies through modulation of the Ca²⁺-mediated autophagy pathway.

Were there any specific challenges associated with this project? If so, how did you overcome them?

There were many challenges. One challenge was standardising the concentrations of pharmacological drugs used in the experiments. I used multiple drugs across various conditions and, although I referred to the existing literature, it still took a considerable amount of time to achieve optimal conditions. Additionally, during the initial phase of the project, I had to spend significant time selecting the most relevant cell line for the study because of the dynamic nature of P-body structures, which vary depending on the cell line as well as on conditions such as nutrient levels and physiological status.

When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?

Yes, of course. When I first inhibited AMPK using a drug called compound C, the P-body number increased dramatically, suggesting the involvement of AMPK in the maintenance of P-body abundance, which was very encouraging. When I showed these results to my supervisor, he was very excited and congratulated me, saying that this could serve as a promising lead for the project's future directions. From that point onward, we dedicated all our efforts to the project, and it turned out to be highly fruitful.

Why did you choose Journal of Cell Science for your paper?

JCS is known for its trustworthiness, ethical standards and authenticity. I personally like the rigorous peer review process that the journal follows, which ensures that the papers have a high scientific impact. Our research was well aligned with the scope of the journal, so we decided to submit our manuscript to JCS. Also, given the reputation JCS has earned in the field, we believe it to be an ideal platform for publishing our findings.

Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?

Yes, my PhD guide Dr Jomon Joseph. He was the one who believed in me; he gave me a chance to learn, fail and learn again. He never let go of my hand throughout the entire journey. I vividly remember how I was when I initially joined the lab and how far I have come now. The immense improvement in my scientific career is all because of him. His words always lifted my spirits. There were many ups and downs along the way, but he stood strong behind me through it all. His great love for science kept him and all the lab members motivated, helping us persevere even when nothing seemed to be working.

What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?

When I was a kid, I was always full of questions, particularly: What is this? Why does this or that happen? I was naturally curious about so many different things. This curiosity motivated me to become someone who helps uncover the answers to the ‘why’ questions in biology. When I completed my master's degree, I decided to pursue those ‘why’ questions by doing a PhD at the National Centre for Cell Science, Pune.

Who are your role models in science? Why?

Abdul Kalam, one of the finest aerospace scientists and the eleventh president of India, is my role model in science. His life was dedicated to science, and his simplicity, purity and authenticity were remarkable. He was an amazing teacher and a motivation for many students and aspirants. His book, ‘Wings of Fire’, is my all-time favourite because it sparks a ‘fire’ in one who reads it. His words, “dream big, work hard and never give up”, are a life lesson that has always kept me going. He emphasised the power to dream.

What's next for you?

I am ready to step into the job market, excited by the diverse and interesting opportunities available across various fields of science. I believe that the knowledge and skills I've gained throughout my PhD journey have equipped me well to make a meaningful impact in the biotech corporate sector.

Tell us something interesting about yourself that wouldn't be on your CV

I enjoy playing outdoor games like cricket and volleyball. I have actively participated in various sport competitions organised at my institute. The physical activity and exercise involved not only kept me focused and energised at work but also brought me an immense satisfaction and a sense of accomplishment after giving my all on the field.