Single-molecule (SM) biophysics provides a peek into the working of fascinating world of biomolecules and cells. While bulk studies only provide us with an average over an ensemble, SM helps us to study a single enzyme or cell at a time. This unique feature helps us in identifying various reaction pathways of the system under observation, which can easily be missed in traditional studies. The main focus of my group is as follows:
Understanding the working of helicases: Helicases are ubiquitous molecular motors operating inside all living organisms. They are vital to our existence as they are involved in almost all NA-related processes including DNA replication, repair, recombination, transcription, and every event of post-transcriptional gene regulation. Their vital functions are illustrated by the fact that mutations in a number of helicase genes can deter the chromosomal stability and hence can lead to either certain hereditary diseases such as Bloom’s syndrome and Werner’s syndrome or on occasions associated with various cancers. Understanding how these mutations affect the kinetics of the helicases with respect to their wild-type counterpart can lead to better understanding towards the cause of such diseases.
Understanding the role of helicases in G-quadruplex (G4) resolution: DNA and RNA can for non-canonical structures that disobey Watson-Crick rule of A-T and C-G binding. Some of the most commonly occurring such non-canonical structures are G4 that can be formed in G-rich sequences. Sequences with G4-forming potential are often found near the replication origins of higher eukaryotes, suggesting a possible role of G4 in the initiation of replication. Highly stable G4 structures could act as kinetic traps that alter efficiency of replication and transcription. This property is utilized in design of G4 stabilizing ligands for anticancer drugs to target G-quadruplexes in the promoters of oncogenes and at telomeres. There are various helicases from SF1 and SF2 that has been associated with G4 unwinding. Among the RECQ family, BLM and WRN are known to effectively resolve G4 and other non-canonical structures.
Explore the kinetics of various CRISPR-Cas Systems.