Research Overview
RESEARCH
Ion channels generate electrical current signals in the nervous system and are central to our perception of ‘Who We are’. Anomalies in their function often lead to disastrous consequences in living organisms. In humans, more than 50 channelopathies, e.g. epilepsy, cystic fibrosis, cardiac arrhythmia etc., have been described which are due to mutations in ion channels and receptors that change their function. Ion channels are one of the major molecular targets of commercial drugs. My research interest has been largely focused on the structure-function of ion channels and their implications in human pathophysiological conditions. My lab employs ‘single channel’ and ‘whole-cell’ patch-clamp electrophysiology, stochastic data analyses, kinetic modeling, protein engineering and experimental data-guided molecular simulation tools to understand ion channel structure and function.
Receptor Engineering
Allosteric proteins like ion channels and receptors exist in at least two distinct functional states: resting (‘R’) and active (‘R*’). The free energy difference between R-R* is the intrinsic ‘gating’ energy (DeltaG0; akin to the saving in one’s bank account). Usually, the R-R* barrier is so high that the channel stays in the R state and rarely opens. The energy from ligand binding, mechanical stress or voltage application changes the gating free energy of the channel (e.g. DGn; n=number of binding sites) by adding a big boost of energy (DGLig/DGVm/DGs; akin to a lottery “jackpot” that swell the saving account) and lower the free energy barrier so that the channel opens at high open probability. Channels are either activated by ligand, mechanical stress or voltage and are accordingly known as ligand-, mechano-, or voltage-gated. We employ the concepts of ‘allostery’, thermodynamics and an array of molecular biology tools to engineer the function of ion channels and neurotransmitter receptors.