Academic Details
Ph.D: Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, Karnataka, India. (2010).
Thesis Title: Chromatin Modifications by CARM1/PRMT4 and p300/KAT3B in the Regulation
of Gene Expression, Probed by Specific Small Molecule Inhibitors
Abstract:
Gene expression is regulated through a myriad of mechanisms, of which chromatin modifications, play an important role. My doctoral research was aimed towards identifying a role of chromatin modifying activators, arginine methyltransferase CARM1 and lysine acetyltransferase p300. This was achieved through an inhibitor based approach. In this context, we identified CARM1/PRMT4 specific inhibitor, TBBD from pomegranate crude extract. The mechanism of enzyme inhibition was found to be unique wherein the substrate sequence determined the specificity of the inhibition. The presence of the proline residue in the substrate sequence in the context of the modification residue led to the interaction of the inhibitor with the ES complex and thereby led to a specific inhibition. This residue (H3 arg 17 methylation) specific inhibition was found even in the physiological conditions. H3 R17 modification was thus shown to be important for gene expression in embryonic stem cells, regulating the astroglial fate specification. Lysine acetyl transferase p300 specific inhibitor, plumbagin was identified and characterized from Plumbago rosea roots. This work led to the identification of a new scaffold for HAT inhibition and most importantly, the identification of the chemical entity essential for acetylation inhibition. Both of these inhibitors were used to understand the combined role of these activation associated epigenetic marks in p53 dependent gene regulation.
Post-graduation (degree): MSc Biotechnology School of Biotechnology, Madurai Kamaraj University, Tamil Nadu, India, 2005 Gold medallist
Graduation (degree): BSc Microbiology and Biochemistry, S.I.E.S college of Arts, Science and Commerce, University of Mumbai, Maharashtra, India. 2003