Protein - nucleic acid interactions
Often nucleic acid binding domains are structurally well conserved but show remarkable adaptability in recognizing different nucleic acids substrates. We are exploring the structure, functions, and folding of nucleic acids binding domains that include RRM, KH, and ARID domains. We employ biophysical tools (ITC, spectroscopy and structural biology (solution NMR spectroscopy and X-ray crystallography) toold and methods to protein these domain and their interactions with DNA/RNA.

Telomere remodeling and maintenance
Telomeres are the protective ends of linear eukaryotic chromosomes that are composed of linear telomeric DNA repeats and proteins (the shelterin complex in vertebrates). Telomere DNA repeats itself form complex secondary structures that include formation of t/D-loop and G-quadruplexes. Remodeling of telomere structure that includes displacement of telomere binding proteins, telomere DNA t/D-loop dismantling, and G-quadruplex unwinding, are critical for telomere DNA replication at the telomere ends. A number of proteins including ‘shelterin’ complex proteins, hnRNAP1, RTEL1, APPOLLO, MRN complex and lncRNA TERRA have been shown to play active role in this process. We are interested in understanding telomere remodeling process by studying protein-protein and protein-nucleic interactions between key players.

Bacterial toxin-antitoxin systems
In this project we aim to understand the structure, functions, and stability of toxin-antitoxin (TA system) modules in bacteria. TA systems play functional role in bacterial drug tolerance and establishment of persister phenotypes. Activation of TA system (using e.g. peptide or small molecule) in pathogenic bacteria can be potentially used as antibacterial therapy. Of the five characterized classes of TA complexes, class II and class III are most prevalent and are focus of our study. Class II TA module consist of protein toxin and antitoxins, whereas class III system has protein toxin and a non-coding RNA antitoxin. We have recently solved structure of type II HigBA TA and type III ToxIN TA systems from E. coli. Currently we are understanding the assembly and activation mechanism of these systems in detail.

FUNDING: We are currently funded by grants from DBT, DST, and IISc intramural funds.