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Cryo-EM studies of TRP channels


EMSL Project ID
51044

Abstract

Transient receptor potential (TRP) channels are a superfamily of calcium-permeable ion channels that are involved in diverse physiological processes. A subset of TRP channels that are known as the thermosensitive TRP channels (thermoTRP) are responsible for sensory transduction in human. They are life’s molecular sensors that detect chemical and physical stimuli (e.g. environmental chemical irritants, cooling agents, and noxious temperatures), and contribute to pain and/or itch sensing in human. Because of their crucial roles in nociception, thermoTRP channels are validated drug target to treat pain and/or itch. However, despite recent advances in structure biology of TRP channels, our understanding of the gating mechanisms of thermoTRP channels is limited, which has hampered drug development targeting these channels. Our goal is to understand the mechanisms of thermoTRP channel gating using cryo-EM.
We have strong preliminary data for each aim, so two years of programmatic access at the PNCC would allow us to make substantial progress toward all aims, which will undoubtedly facilitate our understanding of the gating mechanism of thermoTRP channels, help facilitate drug development targeting these channels, and help understand the role of these channels in nociception at the molecular level.

Project Details

Start Date
2019-10-15
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

Seok-Yong Lee
Institution
Duke University

Team Members

Aili Hao
Institution
Duke University

Feng zhang
Institution
Duke University

Nicholas Wright
Institution
Duke University

Dohoon Kwon
Institution
Duke University

Ying Yin
Institution
Duke University

Suo Yang
Institution
Duke University

Janette Myers
Institution
Oregon Health & Science University

Irina El Khoury
Institution
Environmental Molecular Sciences Laboratory

Trevor Moser
Institution
Environmental Molecular Sciences Laboratory