Investigation of Ion Channel Mechanism


Structure and dynamics of prokaryotic ligand gated ion channel GLIC and ELIC

Pentameric ligand-gated ion channels are responsible for the fast synaptic transmission and play a vital role in many physiological functions. Therefore, the aberration of channel functions lead to several neurological disorders. These ion channels are known to have various functional states with major conformations called resting state, open state and desensitized state or inactivated state. Despite a substantial understanding of the physiological and pathophysiological role of multiple functional states, there is very little structural information available. These channel functions are heavily modulated by membrane lipids and the mechanism of modulation is still illusive. Therefore, the overarching goal of our lab is to understand the mechanism of ion channel functions at the atomic level. Our focus is to study the prokaryotic ligand gated ion channels GLIC and ELIC. We employ multidisciplinary biochemical and biophysical techniques such as Cryo-EM, EPR spectroscopy, and Two Electrode Voltage Clamping (TEVC) to elucidate the mechanism and modulation of channel functions.

Understanding the molecular mechanism of Insect olfactory receptors

Insects such as mosquitoes, ticks, and flies harbor infectious agents and spread deadly diseases like malaria, dengue, yellow fever etc. Dengue is a mosquito-borne viral infection and transmitted mainly by Aedes aegypti mosquitoes. Severe dengue leads to serious illness and causes death. Dengue prevails mostly in tropical and sub-tropical countries like Latin America and southeast Asia including Singapore. Unfortunately, there is no specific treatment for this disease that mandates the development of innovative approaches to control this disease. Instead of developing drug targets for the virus, our lab is focused mainly on targeting the host mosquitoes. Insects use olfactory receptors (ORs) to sense the smell which is critical for their survival. Therefore, we are targeting these receptors to develop newer and most effective repellents. Insect olfactory receptors are non-specific hetero-tetrameric ligand-gated ion channels. Therefore, our goal is to elucidate a clear understanding of the molecular mechanism of insect olfaction which would help to develop new repellents targeting mosquitos like Aedes aegypti.

Support

Start-up Grant, NTU, SBS (2021-2026)

Ministry of Education (MOE), Singapore (2021-2023),

AcRF Tier 1 MOE RS03/21

The National Research Foundation (NRF), Singapore (2022-2027) NRF-NRFF14-2022-0007