First person – Vinay Kumar Dubey

Vinay Kumar Dubey

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

The stem cell are like ‘students’; what they become is influenced by the external cues (such as mentorship and knowledge acquired through their education) and intrinsic factors, such as self-motivation and passion.

Similarly, in this study, we are trying to understand the external cues/signals that drive stem cell to differentiate into specific lineages. One such external cue is the extracellular matrix (ECM), which is a mesh-like network in the body of the animal, where the cells and tissues are embedded. The thickness of the mesh-like network is critical for the maintenance and differentiation of the stem cells. In our study, we identified a transcription factor, ets-1, expressed in the cathepsin compartment, a specialized cell type in the planaria critical for regulating the expression of the factors essential for the maintenance of the thickness of the ECM. When we silence the expression of ets-1, we observed downregulation of factors essential for maintenance of ECM, thereby perturbing its organization. Our study also showed that perturbing ECM led to the failure of stem cells to differentiate into epidermal lineages (equivalent to skin in planarian). This work highlights the important role of ETS-1 in maintaining the ECM structures that are critical for stem cell function.

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

We had a hard time getting good FISH results for ets-1 transcript. This was crucial for multiple experiments in the project. We tried different variations of the in situ protocol, but nothing gave us a good reproducible signal. Finally, we reduced the size of the probe to 120 bases pair in length and used three different non-overlapping probes, which gave us a reproducible parenchymal pattern. This also allowed us to do double FISH with the markers (foxf1 and mt-mmpA), which helped to pinpoint the expression of the ets-1 to cathepsin cells. These experiments helped us hypothesize that the function of ETS-1 was to regulate factors critical for the maintenance of the ECM.

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

Identifying the thickened ECM after ets-1 knockdown was a eureka moment. We used histological sections stained with cellular dyes, which led to the identification of basement membrane thickness. This provided us the interesting leads regarding the function of ETS-1.

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

We wanted to publish our manuscript with a not-for-profit organization, such as The Company of Biologists, which was our first choice. Our previous experience in the lab and with their journals, as well as their fast review process and maintenance of high standard publications are the main reasons for choosing the journal. Another big motivation was the readership of JCS, which overlaps with the target audience for our study.

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

I had to change my mentor and the field of research after two years into my PhD due to personal reasons. I decided to join Dr Palakodeti's laboratory at inStem, which not only gave me opportunity to work again but also rebuild my confidence to stay in science. He has provided me with absolute freedom to plan the project and execute experiments, and he also allowed me to make mistakes, which is a critical part of learning. I was also blessed to be part of an institute with common laboratory setup where discussions were one coffee away. I would specially like to acknowledge my co-author Dr Souradeep Sarkar for being a constant confidant to bounce ideas off. I also benefitted from constant discussions with my thesis committee members, Dr Rajesh Ladher, Dr Akash Gulyani and Dr Tina Mukherjee, who are also experts in the field of cell and developmental biology.

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?

It is hard to pinpoint one reason. I think the complexity and intricacies of biological processes, such as regeneration and development always fascinated me. The most interesting moment, which I can recall, was the first time I cut a planaria and saw them regenerate; a few of them developed two heads and two tails without any genetic manipulation, but this depended on where the amputation was made. That was the day I decided to do my PhD on this animal to understand the processes that drive regeneration.

Who are your role models in science? Why?

There are a lot of scientists whose work has influenced me and driven my pursuit for science. But the statement which influenced me the most was “The victories of science are rarely won single handedly, and no one should get the (entire) credit”, said by Dr Yellapragada Subbarao, also known as the ‘Man of Miracle Drugs’. His achievements have revolutionised the field of medicine, and they include discovery of ATP molecule, synthesis of folic acid, discovery of the antiboitic Aureomycin, the first chemotherapy agent Methotexate, and the tuberculosis drug isonicotinic acid. He remained unrecognized and underappreciated for a long time. To put his contribution into words I have to borrow words from American author Doron Antrim, who writes, “You’ve probably never heard of Dr. Yellapragada Subba Rao. Yet because he lived you may be alive and well today. Because he lived you may live longer”.

What's next for you?

I am currently writing my thesis and on the lookout for a postdoctoral position. I am interested to further explore the role of extracellular matrix, both in stem cell function during regeneration and development, using other regenerative in vivo models.

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

I am an aquarium enthusiast and like to understand animal behaviour. Currently, I share my room with an axolotl, a red ear slider turtle and two community fish tanks. Apart from this, I have been the sports representative for the Bangalore Life Science cluster for the past 5 years and have enjoyed organizing muti-sport tournaments and wining a few of them.