The major line of research in our laboratory aims at understanding the molecular basis of structure-function correlations in ion channels. Ion channels have evolved to undergo rapid conformational changes in response to stimuli and thereby tightly regulate ionic fluxes and thus the cell physiology. They have varied architecture and broadly differ in the nature of stimuli, activation timescales and ionic selectivity. This structural and functional diversity allows them to critically govern the rate, duration and amount of current and as a result impact a multitude of cellular processes.
One of the fundamental challenges in this field is to understand how spatially-separated structural motifs of the channel communicate in order to fine-tune its function. The primary focus of our research is to elucidate the conformational dynamics underlying allosteric mechanisms in ligand- and voltage-gated channels, and to determine how these processes control the basic features of channel function namely, gating and selectivity.
With the discovery of microbial ion channels having strong structural and functional homology to their mammalian counterparts, the ion channel field is currently positioned with a unique advantage to draw direct information from structural, dynamics and functional measurements. Currently, we work on two classes of ion channels; pentameric ligand-gated channel (such as GLIC, ELIC) and Voltage-gated sodium channel (such as NaChBac, NavSp1). We use a multidisciplinary approach that combines single-channel, macroscopic-current measurements, model-based kinetic analysis, site-directed spin labeling, electron-paramagnetic resonance spectroscopy, isothermal titration calorimetry, X-ray crystallography and Cryo-EM. These techniques complement each other and allow, at unprecedented detail, an atomic level description of how structure and dynamics govern protein functioning. In the recent years we have begun to adapt these approaches to more complex eukaryotic channels (such as 5-HT3A, GABA, Glycine receptor) starting with optimizing their expression and yields to carry out structural and functional study.