研究方向：

1) Mechanisms of small-molecule modulation of nociceptive TRP ion channels

2) Modulation of ion channels by animal toxins

3) Computationally design or redesign of proteins to modulate the function of ion channels.

研究内容：

Ion channels are integral membrane proteins that form the basis of electrical excitability of neurons, muscle cells and cardiac cells. Their opening in response to electrical and/or chemical stimuli determines the flow of ions across plasma membrane, which alters the membrane potential to transmit the signal. Ion channels are the third largest protein family that are targeted by small-molecule drugs or biologics. Therefore, understanding the mechanisms of how ion channels interact with ligand is critical for drug development in future.

Our lab studies the nociceptive Transient Receptor Potential (TRP) channels that are the initial detectors for pain. TRPV1 is the receptor for capsaicin, a chemical responsible for spiciness. By combining computational and functional studies, previously we have revealed the atomic details of the structural mechanism of capsaicin activation of TRPV1. To further confirm our understanding of such a mechanism, we transferred vanilloid sensitivity to TRPV2 channel, which is not sensitive to vanilloids like capsaicin or resiniferatoxin, by only four point mutations.

TRPV1 channel is also a noxious heat sensor in our body. However, how are these channels activated upon temperature changes are largely unknown. We found that TRPV1 exhibits large enthalpic and entropic changes during its heat activation. Furthermore, by simultaneously recording of electrical and fluorescence signals from TRPV1 using the whole-cell patch-fluorometry system we built, we observed on the outer pore region of this channel exhibits large conformation during heat activation. This finding laid the foundation for understanding the mechanism of heat sensing.

Toxins from venomous animals like scorpions are of great potential as biologic drugs. We identified the RhTx toxin and BmP01 toxin that activates TRPV1 by manipulating its heat activation and proton activation machineries, respectively. Combined computation docking with mutagenesis, we determined the binding configuration of the toxins on TRPV1 channel.

招生方向：

Pharmacology, Biophysics

研究手段：

Electrophysiological techniques like Patch-clamp recording, single-channel recording; Computational structural biology techniques like protein structure prediction, small-molecule docking, protein-protein docking and protein design; Imaging techniques like Fluorescence Resonance Energy Transfer (FRET) and Calcium imaging.