Research Experience

G-quadruplexes (G4s) are four-stranded motifs formed by G-rich nucleic acid sequences. These structures harbor significant biological importance as they are involved in telomere maintaince, transcription and translation of various proto-oncogenes. For G-quadruplex (G4) structure sensing, we used small molecular fluorescent ligands to sense the G4 structure inside the cancer cells like HeLa and HepG2. We used confocal fluorescence microscopy and flow cytometry based studies to visualize and sense the canonical G4 structures present on the promoter regions of proto-oncogenes like c-MYC and c-KIT.

For G-quadruplex structure stabilizing studies, we used bisindolylmaleimide-based ligands which preferentially stabilize parallel G4 structures of c-MYC and c-KIT oncogenes over the telomeric, h-RAS1 G4 and duplex DNA. The ligand was hight cytotoxic in HeLa and MCF-7 cells and performed qRT-PCR studies to check downregulated c-MYC gene expression. We found out after ligand treatment c-MYC gene expressionlevels decreased 2-3 folds as compared to untreated controls. In conclusion theese small molecular ligands stabilize and sense secondary structures in cancer cells like, with a long term goal to develop nucleic acids targeting therapeutic agents

Ubiquitin activating enzyme (E1) has six domains out of which second catalytic cysteine half domain (SCCH) has catalytic cysteine which forms covalent bond with ubiquitin and ubiquitin fold domain (UFD) serves as binding site for E2. We cloned DNA fragments of SCCH and UFD in MHY 501 strain of S. cerevisiae and overexpressed them. By carrying out functional studies we observed that under stress conditions when the cells accumulate misfolded and truncated proteins, the overexpressed domains reduced the growth and survival of the cells probably due to interference in the proteasomal pathway