RESEARCH

Our research is primarily focused on the calcium ion channels, which are nano-tubes in the cellular and organelle membranes, that maintain calcium homeostasis in the body. Calcium ion channels play essential roles in numerous physiological processes, including firing of action potential, neuronal regulation, and reproduction. Misregulation of these ion channels is implicated in many pathological conditions and, therefore, represent the leading drug target for associated diseases.

Currently, we use cryo-electron microscopy and X-ray crystallography, in addition to other complementary biophysical techniques such as electrophysiology and fluorescence spectroscopy, to elucidate the molecular mechanisms underlying the bases of calcium ion channel function in both normal, and diseased states. Our long term goal is to reveal the structures of calcium ion channels in different gating states and then use this structural information to develop molecular models of their inhibition by pharmacological entities. Going forward, we are particularly interested in harnessing cryo-electron microscopy to determine the structures and subcellular organizations of ion channels isolated from, and visualized directly in diseased tissues, including those from cancerous tissues. This approach will provide unprecedented molecular insights into the roles of ion channels in disease and would substantially accelerate the development of novel drugs.

Calcium signalling in sensory modalities

Transient receptor potential (TRP) super family of ion channel is comprised of 28 members in mammal that play diverse roles in physiology ranging from sensory modalities of body system such as temperature and pain sensation to ionic homeostasis. Temperature affects all the physical, chemical and biological reactions, making it an indispensable entity for sustaining life. Its perception represents the oldest physical ability of all the living organisms, ranging from bacteria to humans, which played an essential role in adaptation, survival, speciation, and evolution of all living beings in their comfort zone. In mammals, thermal perception is mediated by the primary sensory neurons, which have been known for more than a century, however, the molecular sensor of temperature remains enigmatic, until recently, when remarkably, it was found that a member of transient receptor potential (TRP) superfamily of ion channel TRPV1, acts as a thermorecptor. This discovery resulted in the rapid identification of ten other members of TRP channel (shown in rectangular box), collectively called as thermoTRPs that exhibit unusually high-temperature coefficient Q₁₀ relative to non-temperature sensitive channels, allowing them to exquisitely open and close in response to different threshold of temperature. Interestingly, same type of neurons is also responsible for the nociception (pain sensation), further substantiating the importance of thermoTRP as analgesic drug target.