Mr. Kesarwani is currently a PhD student in the lab of Dr. Minhajuddin Sirajuddin at the Institute for Stem Cell Research and Regenerative Medicine (inStem), NCBS, Bangalore. He published a paper titled “Genetically encoded live-cell sensor for tyrosinated microtubules” as the first author in Journal of Cell Biology (2020).
Author Interview
How would you explain your paper’s key results to the non-scientific community?
Our study developed a live-cell sensor that allows scientists to observe tyrosinated microtubules in real-time. Microtubules are hollow, tube-like structures made of alpha and beta tubulin proteins, forming part of the cell’s skeleton (cytoskeleton). They play essential roles in shaping the cell, transporting materials, cell division, and movement.
These tubulins can undergo posttranslational modifications (PTMs)—chemical changes that affect their function. One such reversible PTM is tyrosination/detyrosination, where a tyrosine amino acid is added or removed from alpha-tubulin. This modification regulates interactions with other proteins and is vital for proper cellular functioning.
Dysregulation of tyrosination has been linked to diseases of the brain, heart, and cancer. Traditionally, these changes could only be studied in dead (fixed) cells using antibody staining. Our innovation allows live tracking of tyrosinated microtubules, making it possible to understand their dynamics in living cells.
By fusing our sensor to fluorescent proteins, we visualized microtubules in real time and tested how anti-cancer drugs like nocodazole, colchicine, and vincristine disrupt them. Each drug had a distinct effect, revealing their mechanisms more precisely.
“[…] sensor is superior to all the existing microtubule markers for live cell study […]”
What are the possible consequences of these findings for your research area?
This sensor unlocks a new way to study microtubule PTMs and the enzymes behind them in live cells. It can aid in screening anti-cancer drugs that target microtubules. Most dividing cells have tyrosinated microtubules, so our sensor is well-suited to study cell division and microtubule behavior without interfering with natural functions—unlike previous tools.
What was the exciting moment (eureka moment) during your research?
The eureka moment came when I successfully visualized microtubules in live cells using the sensor. It was challenging to find the right fluorescent tag—commonly used ones like GFP and mCherry didn’t work well. But when I fused the sensor with TagBFP (blue) and TagRFP-T (red), I could clearly see microtubules in real time. That visual confirmation was a breakthrough.
What do you hope to do next?
Our next step is to develop live-cell sensors for other microtubule PTMs such as detyrosination, glutamylation, and acetylation. These tools will help us uncover how these modifications affect microtubule function in various cellular contexts.
Where do you seek scientific inspiration?
My inspiration comes from the challenges in my research and the satisfaction of solving them. Perseverance and patience have always rewarded me with results. I’m also grateful for the mentorship and constructive feedback from peers and supervisors, which help refine my thinking and grow as a scientist.
How do you intend to help Indian science improve?
India has a strong and diverse scientific community, but industrial support is limited. I aim to contribute by developing innovative technologies that bridge academic research and real-world applications. My goal is to generate reproducible and impactful results, such as the live-cell microtubule sensor. I also hope to develop clinically relevant inhibitors and collaborate with industry to ensure our research benefits society and supports economic growth.
Reference
Kesarwani S, Lama P, Chandra A, Reddy P P, Jijumon A S, Bodakuntla S, Rao B M, Janke C, Das R, and Sirajuddin M.
Genetically Encoded Live-Cell Sensor for Tyrosinated Microtubules. Journal of Cell Biology, 2020, 219.
Author Bio and Research Interests
Born in Lucknow, Uttar Pradesh, Mr. Kesarwani completed his undergraduate studies in Delhi and postgraduate studies in Varanasi. Currently, as a PhD student at inStem, Bangalore, his research focuses on understanding how post-translational modifications regulate microtubule dynamics and cell biomechanics, particularly the roles of cytoskeletal proteins.
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