Indian Institute of Chemical Biology, Kolkata
Institute for Biomedical Research, Basel, Switzerland
Indian Institute of Science, Bangalore
My childhood fascination towards wild life, or in that case any living organism led me to study biology. Although, originally I wanted to become a wildlife biologist (or even a wildlife photographer), but as soon as I came to know that the basic features of the genetic material, the mechanism of its readout, and most of the encoded biomolecules are conserved in all the living systems on this planet, I was more intrigued to know the underlying molecular principles which make the similarities between a blue whale and a tiny little plant seedling as striking as their obvious mesmerizing differences.
I landed up in the laboratory of Dr. Samit Adhya in IICB, Kolkata to perform my pre-doctoral studies as I wanted to work on an 'original problem', although I did not have a very clear idea about what is 'original' and what is 'not that original'; but I was persuaded and convinced by my teachers in the University of Calcutta, and soon I realized that luck was on my side in that decision. It was indeed a great learning experience and real privilege to work on the mechanism of mitochondrial tRNA import in Leishmania, which lacks the entire repertoire of mitochondrial tRNA genes, which makes the pathway essential and indispensable for its survival. The very research problem was developed by Dr. Adhya in his own laboratory just from scratch and out of his own inquisitiveness, vision, and over all guts-and-grit to walk a lonely & risky path of working with a neglected disease model Leishmania tropica, which is obviously not a 'hot system' to work with, and that too in a laboratory having some bare minimum infrastructure, which by no means could be defined as 'well-equipped'. So, there I learnt to think 'differently', and rather more importantly how actually one can think 'differently' and get it translated into something of substance. Indeed, it has always been deeply inspiring having worked with someone who created a sphere of research on his own and which has later attracted so many, especially from the west, to join and walk on the trail which he left behind. With his guidance, I also contributed fairly to the pursuit of that endeavor, and it was a rare privilege when a part of my work got selected for presentation in the prestigious Platinum Jubilee Gordon Conference on Mitochondria-and-Chloroplasts, and for which I received a Nature Publishing Group Award (UK) supporting my participation. Later, I also received the INSA Young Scientist Medal for all my pre-doctoral research contributions.
While I was performing my pre-doctoral research with tRNA-and-mitochondria, actually a lot of exciting things were happening in the field of RNA research, although no one could imagine at that point of time that the field was on the verge of an explosion of discoveries of major new functions of RNA, and that too the non-coding ones. In those days, outside the conventional roles, any other possible roles of RNA were not anticipated at all, but, nevertheless, the discovery of RNA interference (RNAi) and microRNA (miRNA) mediated developmental regulation brought a paradigm shift to the prevailing perception, and opened the flood-gate for the discovery of additional non-coding RNAs and their functions, which continues to this date. Most strikingly, I was quite astonished to know that the non-coding RNAs are way more abundant than the coding mRNAs, and they actually confer a great deal of regulation towards the expression of those mRNAs, and this is well evident from the dramatic increase in variety and abundance of the non coding RNAs during the course of evolution, whereas the coding mRNAs remain largely static during that journey. And this context was good enough to help me make up my mind that I should venture into this vast unknown world of non-coding RNAs, especially small non-coding RNAs, and miRNAs to be very specific.
When I started as a post-doc at FMI (Basel, Switzerland), efforts in the miRNA field were highly focused on identifying targets of miRNAs and the mechanisms they employ to regulate those targets. Since, the environment of my PhD-life had already inculcated a strong urge in side me to do something completely new and different, and create a path of my own during my post-doctoral tenure itself, I proposed to focus, instead, on regulation of the miRNAs themselves. In fact sailing against the existing dogma of 'super-stable' mature miRNAs, I specifically asked whether a miRNA turnover pathway exists that could modulate miRNA expression patterns post-transcriptionally, potentially even reversing target gene silencing. Again it was a great privilege for me that two major international funding agencies supported my endeavor by two of the most prestigious international fellowships (Marie Curie International Incoming Fellowship of EU and EMBO Long-Term Fellowship).
I achieved all my preliminary goals and my results confirmed the presence of an additional layer of regulation of animal miRNA activity through miRNA turnover that might be crucial for bringing in rapid changes in miRNA expression profiles during developmental transitions and for the maintenance of steady-state concentrations of miRNAs, and it could also be opined that the turnover pathway facilitates the process of evolution of miRNAs. I was awarded with the Max M Burger Prize (Switzerland) for this fundamental research, and this was really gratifying as I always looked up to the Swiss people with a complete awe for their endless quest for perfection and precision.
To my satisfaction, recently there have been waves of reports revealing that the stability of miRNAs can be regulated through differential turnover, with miRNA identity and tissue of expression affecting miRNA half-lives, and even implicating that the turnover pathway might be the major governing factor towards determining the abundance and activity of miRNAs. Although, the initial findings have spawned a new sub-field in miRNA research, but a complete understanding of the pathway & the modus operandi, followed by unraveling of the mechanism of differential regulation of the pathway components would create the platform from where future translational research would be possible. And in the coming days, through my work, I aspire to continue to be a major contributor towards that goal, which has originally been set by me.