Description:

Title: “Sensing Coolness and Cold: Mechanism of TRPM8 Gating.”

Abstract: We have a long-standing interest in understanding how humans sense thermal and chemical stimuli through ion permeation via Transient Receptor Potential (TRP) ion channels. The TRPM8 (Transient Receptor Potential Melastatin 8) channel is the primary molecular transducer responsible for the sensation of coolness induced by menthol and cold temperatures in mammals. Additionally, our sensory adaptation to cold is mediated by the desensitization properties of TRPM8 channels. TRPM8 is also implicated in cold-evoked pain disorders and migraines, making its inhibitors a promising avenue for pain relief. Understanding the mechanisms of TRPM8 activation and desensitization by cold is not only a fundamental question but also has significant potential for therapeutic development. We have elucidated the structural and mechanistic bases of TRPM8 activation, desensitization, and inhibition. Our findings shed light on the molecular mechanisms underlying cold sensation and adaptation in mammals, as well as highlight the therapeutic potential of TRPM8 in treating neuroinflammatory diseases and cold-evoked pain. 

Brief summary of Dr Lee's research: Membrane transport proteins selectively recognize a variety of substrates of differing sizes and physicochemical properties for cellular transport, making them essential for the movement of key molecules and the transfer of information across cell membranes—events central to many important physiological processes. We utilize various structural and biophysical methods—including cryo-EM, electrophysiology, and radioligand flux and binding assays—to study three important transport processes: temperature- and irritant-dependent ion channel gating, drug and nutrient transport and inhibition, and polysaccharide transport for microbial cell wall synthesis. Studying these systems helps us understand the physiological and pathophysiological processes underlying somatosensation, pain, cancer, and bacterial or fungal infections.

Guest Speaker: Seok-Yong Lee, PhD; George Barth Geller Distinguished Professor of Molecular Biology; Professor, Departments of Biochemistry & Cell Biology; Member of the Duke Cancer Institute.