Deciphering the molecular mechanisms of temperature and pain sensing by TRP channels

The abili­ty to per­ceive tem­pera­ture is cru­cial for expe­rien­cing pain and plays a fun­da­men­tal role in our sen­sory world. Certain members of the tran­sient re­cep­tor po­ten­tial (TRP) channel su­per­fa­mily act as di­rect thermo-sensors and pain re­cep­tors, ope­ning pros­pects as tar­gets for ad­dic­tion-free pain therapy. The molecular me­chan­isms through which thermoTRPs de­tect tem­pera­ture changes remain unk­nown. We will de­cipher the molecular me­chan­isms of TRP-in­vo­ked noci­cep­tion, pain, and thermal sen­sati­on.

The Junior Research Group "De­ciphering the molecular me­chan­isms of tem­pera­ture and pain sen­sing by tran­sient re­cep­tor po­ten­tial channels" will de­velop in­no­vati­ve me­thods in membrane pro­tein bio­che­mistry and cry­o-e­lect­ron micros­copy (cry­o-EM) as a structural bio­logy tool to de­cipher the enigmatic molecular me­chan­isms of TRP channel-invo­ked sen­sing of pain and tem­pera­ture.

Cry­o-EM has evol­ved as a pow­erful tool to gain near-atomic reso­luti­on in­sights into the molecular ar­chi­tec­ture of membrane pro­teins such as TRP channels. Un­der the right bio­che­mi­cal/bio­phy­sical con­diti­ons, cry­o-EM can re­solve mul­tiple sta­tes of the pro­tein thus fos­tering our un­der­standing of the molecular me­chan­ism of me­dici­nes or en­vironmen­tal sti­muli such as tem­pera­ture on these channels.