Research

Ion channels are vital for various cellular signalling processes and are important drug targets. These fascinating cellular nanomachines conduct super-fast permeation of ions across the membranes close to the diffusion limit (~100-1000 million ions per second).  It is fascinating to study the molecular mechanism of gating, selectivity and permeation  We are interested in understanding the structural dynamics of ion channels in different functional states in the physiologically-relevant membrane environment.  Although significant advances have been made in the structural biology of membrane proteins and lots of high-resolution structures (X-ray and cryo-EM) are available, most of the structures were determined in detergent micelles due to technical difficulties.  We focus on lipid-protein interactions as the major determinant of the membrane protein function since it is well-established that membrane lipid composition shape the conformational landscape of membrane proteins and their functional attributes.  

We work on various projects, which include the gating-induced conformational dynamics of Mg2+ ion channel, MgtE and its homologs, structural dynamics associated with the lipid-dependent gating of the voltage sensor of the voltage-gated K+ channel, KvAP and Inward rectifying potassium (Kir) channels.  Further, our research involves understanding the nature and mechanism of Mg2+ sensing  by MgtE channels.  We use molecular biology, biochemical, and sophisticated biophysical approaches, particularly the Site-directed fluorescence & EPR, and Dynamic Light Scattering (DLS) measurements along with ion transport functional assays.  We use various membrane-mimetic systems such as micelles, liposomes and Nanodiscs to understand the role of membrane-mimetic systems in the structural dynamics of ion channels.  Further, we also work on method development like cost-effective purification of membrane proteins utilizing the 'dual-detergent' strategy, ion binding assays and fluorescence-based liposome flux assays.  We are now attempting to do the structure determination of our newly characterized MgtE homologs using single particle analysis and cryo-EM. We also collaborate for performing MD simulations to understand the intricate details of these membrane transport proteins that are not accessible by experiments.