# Structure and function of Transient Receptor Potential channels

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $383,699

## Abstract

PROJECT SUMMARY
Transient Receptor Potential (TRP) channels are regulated by a broad range of stimuli, including chemicals,
temperature, mechanical stress and membrane voltage and are directly involved in the perception of sensory
modalities such as vision, taste, olfaction, hearing, touch, temperature and pain. TRP channels are implicated
in the pathogenesis of numerous diseases and some of them represent important prognostic markers and
promising targets for new therapeutic strategies to treat a variety of human cancers. For efficient drug design,
we need detailed information about TRP channel structure and function. We plan to study TRP channel
structure and function using a combination of different biophysical and biochemical methods. Our specific aims
are: 1) establish molecular bases of TRP channel regulation by calcium, 2) determine the molecular
mechanism of TRP channel gating, and 3) develop molecular models of TRP cannel inhibition by various
organic and inorganic molecules. TRP channels are challenging targets for structure-functional studies
because they represent multimeric integral membrane proteins of a large size with typically low expression
levels. To achieve our goals, we will use a combination of structural and functional approaches including
modern crystallographic techniques, Fluorescence-based Size Exclusion Chromatography (FSEC), calcium
imaging, fluorescent spectroscopy and electrophysiology. We will use different crystallization methods and
temperatures, screen detergents, lipids and ligands to obtain structures of intact TRP channels in different
conformational states. We will then combine the nascent structural information with functional data to discern
mechanisms of TRP channel regulation and gating. Achieving our aims will have a significant impact on
sensory biology and will result in a new structural/functional model of TRP channel that can serve as a
dynamic template for theoretical prediction, in silico fitting and chemical synthesis of new drugs.

## Key facts

- **NIH application ID:** 10073334
- **Project number:** 5R01CA206573-05
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Alexander Sobolevsky
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $383,699
- **Award type:** 5
- **Project period:** 2017-01-12 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10073334

## Citation

> US National Institutes of Health, RePORTER application 10073334, Structure and function of Transient Receptor Potential channels (5R01CA206573-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10073334. Licensed CC0.

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