Research Projects

The National Institutes of Health (NIH) has raised concerns over the use of opioids and suggested the development of a new class of analgesic drugs. The ability to sense temperature is closely linked to pain perception, as the same type of neurons mediate temperature and pain perception. In mammals, thermal and pain perception are mediated by somatosensory neurons that harbor specialized temperature-sensitive Transient Receptor Potential channels called thermoTRPs as molecular thermosensors. These thermoTRP channels represent a valuable analgesic target for alleviating pain. However, the biochemical identity of the thermosensing domain in TRPM3 channels remains elusive due to the absence of the structure of its temperature-activated state. Additionally, the molecular mechanisms underlying how GPCRs form a functional crosstalk with thermoTRPs remain enigmatic, restricting the development of novel analgesic drugs. The proposed research aims to fill this knowledge gap by elucidating the mechanisms by which lipids and G protein βγ subunits regulate homotetrameric and heterotetrameric thermoTRP channels from mammals. The study will also determine the cryo-electron microscopic (cryo-EM) structure of homotetrameric and heterotetrameric TRPM3 channels at different temperatures and their complexes with G protein βγ subunits. The proposed study on the molecular regulation of noxious heat receptor, TRPM3, has great potential for the design of better analgesics against chronic pain. Structural studies on obtaining the temperature-activated TRPM3 will greatly enhance our understanding of the molecular mechanisms of pain and temperature sensation.