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Education- B.Tech. (Hons.), Biotechnology and Biochemical Engineering, IIT Kharagpur (2001)
- Ph.D., Biophysics and Computational Biology, University of Illinois, Urbana-Champaign (2007)
Courses- CH 205 Chemical Reaction Engineering
- CH 248 Molecular Systems Biology
ResearchHow do events taking place at the molecular level translate to biologically significant phenomena?
We develop single molecule and nanoscopic optical imaging techniques to understand this basic question. Using highly sensitive detection of single biological macromolecules like proteins or nucleic acids by both optical and non-optical methods, we determine the molecular behaviour at the single molecule level as well as its distribution at the population level. Our research interest spans the self-assembly of viral particles to the dynamics of RNA dependent RNA Polymerase.
Viral Self Assembly
Virus particle generation is a classical example of self-assembly which is amenable to targeting by drugs. However, in absence of quantitive assays that probe kinetics of the assembly process and its dependence on the role of parameters like pH, salt concentration and protein-nucleic acid allostery, we have seen limited progress made for anti-virals against the viral structural proteins. Our goals here are:
a) to develop techniques that allow characterization of structural dynamics of macromolecular assemblies at the nanometer scale with sub-second time resolution.
b) to probe the Dengue virus capsid assembly at the single virus level in real-time and probe the role of protein-nucleic acid allostery.
Single Molecule RNA Polymerase Dynamics in Living Cells
Mechanistic understanding of the viral replication process by RNA dependent RNA Polymerases (RdRPs) inside the cells is complicated as it is inherently stochastic. It initiates from a small number of single stranded (ss)RNA molecules (sometimes just one) during its initial phase (i.e. during negative strand synthesis). Complexity further increases as RdRP compartmentalizes in membrane-bound heterogeneous structures for positive strand synthesis from double stranded RNA. Furthermore, RdRP regulation arises from phosphorylation, structural changes or transient interactions with other viral/host proteins that generates a heteroge-neous population of replication complexes. It is unclear how such diverse phases of replication are regulated to ensure efficient replication during the infection cycle. To address these issues, we are developing spectroscopic and imaging tools to study inter-molecular and intra-molecular dynamics in living cells with single molecule sensitivity.
Awards & Honors- Innovative Young Biotechnologist Award, Department of Biotechnology, India, 2013
- Jane Coffin Childs Memorial Post Doctoral Fellowship, 2008-2011
1. ZW Zhao*, R Roy*, JCM Gebhardt*, DM Suter*, AR Chapman and S Xie, Spatial organization of RNA polymerase II inside a mammalian cell nucleus revealed by reflected light-sheet super-resolution microscopy. PNAS (USA), 111(2):681-6 (2014).
* equal contributions
2. R Roy, Next generation optical microscopy. Current Science, 105(11):1524-36 (2013).
3. JCM Gebhardt, DM Suter, R Roy, ZW Zhao, AR Chapman, S Basu, T Maniatis and S Xie, Single-molecule imaging of transcription factor binding to DNA in live mammalian cells. Nature Methods, 10(5):421-6 (2013).
4. R Zhou, A Kozlov, R Roy, J Zhang, S Korolev, T Lohman and T Ha, SSB Functions as a Sliding Platform that Migrates on DNA via Reptation. Cell, 146(2): 222-32 (2011).
5. G Tang, R Roy, T Ha and S Patel, Kinetics of Transition to Elongation Phase by T7 RNA Polymerase. PNAS (USA), 106(52): 22175-80 (2009).