Research Highlights
As an interdisciplinary research group, We amalgamate our knowledge of physical sciences, biological sciences, nanoscience and instrumentation in our research. We aim to explore the mechanical strength of different kinds of chemical and biological bonds quantitatively and utilize these knowledge in designing smart materials.
Deciphering the force dissemination mechanism in hearing
Cadherin mediated tip-links (Cadherin 23 in alliance with protocadheirn 15) connecting two stereocilia on top of hair cell in inner ear serves as gating springs for mechanoresponsive ion channels which open beyond a threshold force and convert sound induced mechanical force into electrical signal which our brain can decode. We aim to understand how the tip-link withstand this long range of forces and enable a proper hearing as well as how disease causing point mutation in these two proteins change the structure and force sensing behavior of the complex. We first attempt to understand the unbinding kinetics of the tip-link complex against force using single molecule force spectroscopy and to see the structural dynamics we use single molecule FRET using TIRF microscopy.
Tracking Real-time Dynamics of an Enzymatic Reaction at the Single Molecule level
Quantum-mechanical tunneling of electrons, protons or hydrides have been influential in enzyme kinetics. Our method has the potential to experimentally verify the tunneling efficiency at modulated barrier-heights and/or widths in enzymatic reactions. Information gained from these experiments can further be used for de novo designs of enzymes with enhanced catalytic efficiency.
Strong aggregation index of Cadherin-23 inhibit cell migration
Cadherin-23 is expressed most human tissues at par with classical cadherin, have a high aggregation index compared to classical cadherins like E-cadherin. They were observed to be present in adherent juctions and down-regulated in different solid cancers. They were observed to inhibit cell migration, however, their regulation in cancer cell metastasis is still under investigation.
Molecular mechanism of the strong cell-adhesion by Cadherin-23
A long-chain non-classical cadherin, cadherin-23 (Cdh23) has been reported to attribute the homophilic interactions at the cell-cell junction of breast cancer cells (PLoS ONE, 2012). We identified the molecular structure of the homodimer complex that can mediate stronger cell-cell junction than classical cadherins. Surprisingly, crystal structure was solved in the monomeric form (Neuron, 2012). We observed an extended overlap between the last two domains of Cdh23 that is atypical to classical-cadherins known so far. We used various of biophysical and biochemical assays including SAXS, FRET, anisotropy, and mutational modifications.
Engineering biomolecules using sequential enzymatic stapling and cut
We have developed a method of tailoring small biomolecules, protein to their polymeric form which serves as a substrate for protein unfolding studies at a single molecule level using AFM. This method will be useful for many other applications like synthesis of viral polyprotein which are otherwise inaccessible because of their stability issue, synthesis of chimeric polyproteins of controlled length and of desired sequence
