March 5, 2019
Congratulations to Matan Geron for winning the March 2019 JBC SMART Brain Prize for the outstanding article: “TRPV1 pore turret dictates distinct DkTx and capsaicin gating”, published in Proceedings of the National Academy of Sciences in October 2018.
Matan is a PhD student in Dr. Avi Priel’s lab from the institute for drug research at the school of pharmacy, faculty of medicine. His work focuses on the activation mechanism of pain receptors, mainly the ion channels that are responsible for the detection of noxious stimuli. Those channels evoke the initial depolarization in sensory neurons to produce pain sensation. Specifically, he investigates the structure and function of these ion channels using highly selective and potent toxins from plants and animals. To this end, he employs molecular biology, biochemistry, live-cell calcium imaging and electrophysiological methods. As current pain relief therapies are lacking, thorough understanding of the mechanics that govern the activity of ion channels implicated in pain could pave the way for the development of improved analgesics.
The TRPV1 channel, found in sensory neurons, responds to noxious stimuli from multiple sources to produce an appropriate pain response. However, how different stimuli evoke distinct pain sensations through TRPV1 remains unclear. We found a channel domain (the pore turret) that imposes opposite effects on the responses of TRPV1 to capsaicin (the “hot” ingredient in chili peppers) and the tarantula toxin DkTx. While this domain restricts ion flow through the channel when it is activated by DkTx, it stabilizes the opening of TRPV1 evoked by capsaicin. Overall, our findings reveal that a TRPV1 domain regulates channel activation evoked by different molecules, thus producing distinct subsequent pain responses.
The upcoming deadline for the next SMART Brain Prize is May 31, 2019
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