First person – Poulomi Banerjee

Poulomi Banerjee

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

Messenger ribonucleic acid (mRNA) is a single-stranded RNA molecule synthesized in one compartment of a cell (i.e. nucleus) and transported into the other compartment (i.e. cytoplasm), where it is translated into a protein. Export of mRNAs from the nucleus to the cytoplasm is a critical regulatory step. In recent years, dysregulated mRNA export has been linked to the development of cancers and neurodegenerative diseases in humans. Although there is a general understanding of the mechanism of mRNA export, the molecular details still remain elusive. In the present study, we found that DDX19, an RNA-binding protein involved in mRNA export, is post-translationally modified by SUMOylation – addition of a ubiquitin-like protein called SUMO. SUMOylation enriches DDX19 at the nuclear envelope, where the exported mRNAs are remodelled and released into the cytoplasm. Attachment of SUMO also enhances the interaction between DDX19 and Gle1B, the activator of DDX19, thereby modulating the function of DDX19 in mRNA export. The study provides a molecular basis for further understanding the regulation of mRNA export.

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

Solving any scientific problem inherently is a great challenge. In my project, there were many such instances, but a few of them are worth noting. First of all, detecting SUMO modification of a protein is tricky owing to the low abundance of the SUMO-modified form. Also, the quick transition of a protein between the SUMOylated and deSUMOylated states makes it difficult to capture the protein in its SUMOylated form. Increasing the starting material, quick lysis, use of appropriate inhibitors and shortening the time of the immunoprecipitation assay solved the issue to a great extent. Secondly, separation of nucleoplasm from the nuclear envelope during subcellular fractionation was a very delicate step that required extensive standardization. Finally, during the mRNA export assay, dealing with considerable cell death arising due to toxicity of transfection reagents was another problem. This was resolved by shifting to a cell line in which higher transfection efficiency could be achieved with lower doses of transfection reagents.

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

Yes! I still remember that moment when we found DDX19 SUMOylation affecting its subcellular localization. This observation laid the foundation for the functional relevance of the story, prior to which we were clueless with regards to the role of SUMOylated DDX19.

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

Journal of Cell Science is a reputed journal that grabs attention of scientists due to its wide array of interesting publications. Previously, some of my lab colleagues have also published their findings in JCS, and we were very impressed with the thorough and swift handling of the manuscript. We believe publishing in JCS will allow our findings to reach a broader readership. Apart from publishing research, JCS provides a platform to young researchers to express their views on science and research through the ‘First person’ interview series.

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

My sincere gratitude goes to my PhD mentor Dr Jomon Joseph for introducing me to the exciting world of research. He has not only guided me with his novel scientific ideas and technical expertise, but has also encouraged me to be an independent and critical thinker. During the pandemic, when everything around seemed negative, it was his enthusiastic support and motivation that kept me going. I was fortunate to have my senior colleagues – Santosh and Indrasen – who taught me how to successfully perform the challenging SUMOylation experiments during my initial years. Exchange of scientific ideas with lab members during weekly meetings helped in shaping up my project. My sincere thanks to Dr Vasudevan Seshadri for his thought-provoking questions and insightful discussions during journal club meetings with his lab.

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?

During my high school days, I was very fascinated to handle a compound microscope and visualize different cellular specimens, especially to identify the various stages of mitosis and meiosis. When I came to college, I was thrilled to learn a simple-looking cell is so complex to understand. I wondered how much research goes into understanding biochemical pathways or delineating molecular mechanisms governing cellular functions. The question that puzzled me most was how do people uncover the unknown processes occurring within a cell. The only way to solve that puzzle was to get into it and learn from people who are already in the process of exploring the unexplored. Now that I am myself into that, I realize solving one question raises many others, and thus this endless and fun-filled exploration continues.

Who are your role models in science? Why?

My role models are all those scientists who spend countless years of their life trying to find answers to the world's toughest unknown questions. The most important thing to learn from them is: ‘Don't fear failure’. They know how to fail over and over again and still wake up each day, full of energy, ready to do it all over again. Curiosity, patience, hard work and dedication for science – these qualities are worth learning from any scientist around us. Although there are many inspiring stories around, I am personally motivated by Nobel laureates – Marie Curie and Stanley B. Prusiner.

What's next for you?

I am currently looking for a post-doctoral position to continue my research training, and develop new skillsets and expertise in the field of cell biology.

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

I love to travel, explore nature and visit places of historical significance. Practicing yoga and watching stand-up comedy are my stress busters.

What advice would you like to give to the newcomers in the field of research?

Research is a wide, unknown terrain where it is normal to feel unproductive at times. On such occasions, don't give up; one cannot truly enjoy success until one has tasted failures. Get up, dust yourself off, take a short break, talk to your friends and dive straight back into your work. The way to succeed is to push the failures aside and re-emerge like a phoenix.