Mechanistic understanding of the thermosensitive Transient Receptor Potential (TRP) channels.

点击翻译按钮获取中文摘要

Transient Receptor Potential (TRP) Channels are transmembrane proteins that detect and transduce physical and chemical stimuli. They are involved in various sensory function of the nervous system including vision, taste, pain perception and thermosensation. My research program focuses on the molecular pharmacology of the Thermosensitive families of TRP channel that detect heat, cold and warm temperature. At the molecular level, TRP channels are formed of four pore-forming subunits that assemble into the cell and function at the cell surface to control the flow of extracellular calcium across the plasma membrane. My long term objectives are to gain insight into the biological mechanisms that regulate the function of thermosensitive TRP channels. We employ multidisciplinary approaches including state of the art imaging, electrophysiology, molecular techniques to study the biogenesis and cell surface expression of these channels. We also aim to understand how environmental and endogenous factors (i.e hormones, cytokines and neurotransmitters) modulate the trafficking and the activity of these channels. The proposed project focuses on the heat sensitive TRPV1 channel also activated by capsaicin, the ‘hot’ compound from chili peppers. As a calcium-permeant channel, TRPV1 is involved in specific calcium-dependent signalling pathways that modulate neuronal communication in sensory processing. Our proposal will identify the Ca2+-dependent processes that control TRPV1 channel assembly in the ER, trafficking to the plasma membrane and signalling to the nucleus where gene transcription is regulated. Our work will develop a framework for understanding thermosensation and sensory adaptation to noxious thermal stimuli. This project relies on considerable expertise and preliminary data that I have obtained as a postdoctoral fellow and an assistant professor at the University of Calgary. Our findings will establish a basis for new lines of research which I will use to build a strong training program in a stimulating research environment. This will create opportunities for graduate and undergraduate students and foster the development of scientific knowledge.