Max-Planck-Institute for Molecular Physiology, Dortmund, Germany
Institute for Stem Cell Biology and Regenerative Medicine (inStem)
My interests towards structure-function of genes can be traced back to my Masters time at the University of Madras. It was an interesting period where the first draft of human genome was completed. I was introduced to the concept that each gene encodes a protein molecule, which has its own unique three-dimensional form and shape (protein structure). I also learned about the Anfinsen’s hypothesis that the instructions for forming (folding) a particular form and shape for a protein molecule is encoded in the protein sequence. Together, I wondered about predicting protein structures without experimental methods. Great progress has been made in recent years, although I never pursued this line of research and it seeded my interests in structural biology and desire to study biological processes at molecular level. In my quest to understand protein structure and folding I joined Prof. Varadarajan’s lab at MBU, IISc after completing Masters in Biochemistry. This was my first research laboratory experience and I was immediately hooked with this exhilarating experience, I am grateful to Prof. Varadarajan for this opportunity. As a junior research fellow, I was involved in understanding the factors that contribute to protein stability (keeping protein molecules in its form and shape). The project relied heavily on previously determined protein structures using X-ray crystallography, which furthered my interests in structural biology and I was fortunate to find such a project for my PhD thesis.
After my short stint at MBU, I moved to Germany to join International Max-Planck Research School at Dortmund, Germany. For my graduate work I choose to work with Prof. Wittinghofer, his lab was a Mecca for studying Ras related GTPase proteins and had excellent infrastructure for structural biology. Therefore, I took on the formidable problem of septin filament assembly. Septins are GTP-binding proteins, an enigmatic class of cytoskeleton that assembles into filaments. At that time there was no information on its structure, assembly principles and architecture of septin filaments. Despite my initial success in crystallizing septins, I was unable to determine its structure and was stuck at this ‘phase’ for a very long time. It required persistent effort and unconventional approaches to crack this problem, which equipped me to look out for challenging postdoctoral project.
Ever since I started working with septin filament, I developed a great deal of interest in actin and microtubule cytoskeleton. Prof. Vale’s lab at UCSF has pioneered the combination of biophysical, structural and cell biology to tackle motor proteins; therefore I expressed my wish to Prof. Vale to work on microtubule motors. My initial years in the Vale lab were devoted in learning single molecule TIRF microscopy, this was my first microscopy experience which gravitated me towards in vitro reconstituted system using purified components. At the same time I was also exploring various options to purify recombinant mammalian tubulin/microtubule. With the help of Dr. Rice (UTSW, Dallas), we engineered a chimeric tubulin, which represents the first recombinant mammalian microtubule. This was a breakthrough in the microtubule field and allowed us to study the function of tubulin diversity in particular the regulation of microtubule based intracellular transport at molecular level.
Recently I joined inStem Bangalore, as an independent researcher I aim to study the effects of tubulin PTM on microtubule growth and dynamics. As a part of cardiovascular biology and diseases team at inStem I also intend to study genetic mutations that have been implicated in cardiomyopathies. This is a new direction of research, where I will purify sarcomere components to study the effects of cardiomyopathy mutations. Although I have not worked with actin cytoskeleton before, my experiences in dealing with other cytoskeleton proteins and expertise in structural biology and reconstituting in vitro system will help this new line of investigation. I am happy that the Wellcome-DBT IA reviewers and committee members also felt the same way, which has instilled great confidence to tackle this exciting problem.