Medical College of Georgia (Georgia Regents University), USA
Tata Institute of Fundamental Research, India
I have always been interested in studying fundamental cellular processes that can be applied to most cell types. I believe that in order to cure a disease it is essential to first understand the normal mechanism by which the cell functions. My PhD research focused on studying the mechanism by which messenger RNAs are localized to specific cellular regions. We were interested in studying one such developmentally important mRNA, oskar, which localizes at the posterior region of the Drosophila oocyte. Our lab mainly used Drosophila genetics along with other in vivo approaches to study this process. It was earlier shown that transport of oskar mRNA requires microtubules and microtubule plus end motor Kinesin. Surprisingly, our work showed that transport of this transcript not only requires Kinesin but also requires an opposite polarity motor, Dynein. This was when I got extremely interested in studying molecular motors. In particular the working of the Dynein motor deeply fascinated me.
Although cytoplasmic Dynein was discovered almost three decades ago, as compared to Kinesin, the mechanism of Dynein function remains poorly understood. This has to do with its huge structure and its complex regulation pattern. I gradually realized that in order to perform mechanistic studies with these motors, one needs to complement in vivo biological approaches with some of the powerful physics based in vitro techniques. My postdoc in Dr. Roop’s Mallik lab at TIFR is the first step in that direction.
Dr. Mallik’s lab provides a highly favorable environment to closely study motor-based transport using an in vitro setting. Here we extract latex bead phagosomes (LBPs) from Dictyostelium and study transport of these LBPs using optical trapping on in vitro polymerized microtubules. Optical trapping is an extremely valuable technique. It provides tremendous information about various physical properties of motors (such as their force generation, velocity, processivity etc.), which is generally difficult to predict from other in vivo techniques. I strongly feel a combination of these biophysical measurements along with other biochemical techniques will provide a holistic view of the motor-based transport in the cell.
My aim is to gain expertise in using these new techniques and acquire a skillset that is very different from what I have pursued. My long-term goal is to use this integrative approach to bridge existing gaps in field of cellular biology and understand broadly how cellular transport occurs. Funding from Wellcome DBT has definitely been a stepping-stone towards my goals. It has not only helped me become more independent but has also provided me an excellent platform to explore various avenues that are currently beyond my field of research.