The group is focused on three main areas of research:

 

a) Understanding the structure of nucleic acids (DNA and RNA) and developing novel ligands to target specific structures  

b) Use of nucleic acids and modified nucleic acids as therapeutics and diagnostics

c) Creation of  novel nanomaterials for therapeutic purpose and understanding their interaction with living cells 

 

G-quadruplex-duplex competition:

        It has long been recognized that G- and C-rich nucleic acid sequences can adopt intermolecular or intramolecular four-stranded secondary structures known as quadruplex or tetraplex that often show some functional role. On the other hand, in the genomic context, multi-stranded DNA secondary structure formation in the region other than the end of a chromosome is in competition with the normal Watson–Crick (WC) duplex structures that are formed by the interaction with the complementary strands. However, as the genetic information encoded by DNA must be passed on to the next generation through duplex melting (strand separation followed by replication), there should be presence of interconversion between these multi-stranded secondary structures and WC duplex structures in vivo. In this context, presently we are interested to decipher the mechanism for the interconversion between these quadruplex structures and WC duplex structures. As a part of this study, we are synthesizing small molecules that target quadruplex selectively and specifically over duplex in a given structural competition.

    Despite the growing body of evidence for the existence of quadruplexes in biological systems, their overall functional relevance is still under debate. This is particularly true for the role of quadruplexes due to the competition between quadruplex formation by one strand and hybridization of the two complementary strands. Unlike DNA, transcribed RNA is exported to the cytoplasm, where it experiences more changes in the concentration of ions and molecular crowding agents than DNA existing solely in the nucleus. This suggests that RNA quadruplex may have better relevance than DNA quadruplex and can act as tuneable devices depending on the cellular conditions. On this notion we are also working on RNA quadruplex of functional relevance.

Biophysics and Biotechnology of modified oligonucleotides:
 

    In theory, the concept of executing oligonucleotide-based antisense and antigene strategies seems quite feasible, where high-affinity hybridization between the oligonucleotide and the target strand serves to alter or inhibit gene expression. But, in practice, the use of these strategies has fallen from favor because of the difficulties faced in predicting (i) the accessible sites or structures of the target against which the oligonucleotide has to be directed, (ii) the optimum dose levels required by the agent to act without mediating any toxic effects, and (iii) the inherent weaknesses associated with the oligonucleotide, particularly, specificity and biostability issues. The factors listed above have acted as triggers to uplift the development of novel, structurally modified oligonucleotides that could act as potent and more selective therapeutic agents. One of the most promising candidates of chemically modified nucleotides developed in the past few years is the locked nucleic acid (LNA). However, the existing biophysical knowledge of hybridization thermodynamics of LNA, other than Tm measurements, is limited. Currently we have undertaken detail biophysical studies to characterize the hybridization thermodynamics of LNA-substituted oligonucleotides, to account for their high binding efficiency toward the complementary strand. Investigating hybridization thermodynamics of modified oligonucleotides will aid in predicting their stability that will allow us to formulate guidelines for the optimum design of LNA based oligonucleotides such that maximum functional efficiency could be drawn out of minimum modification. We also use different chemically modified oligonucleotides to alter gene expression.