# Advancing cryo-EM technology to address difficult biological questions

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $321,844

## Abstract

ABSTRACT
Technological breakthroughs in single particle cryo-electron microscopy (cryo-EM) have enabled atomic
structure determinations of many challenging biological macromolecules in an unprecedented rapid pace. It also
facilitated addressing challenging structural biology questions that would otherwise be difficult to address.
Beyond atomic structures, protein dynamics and conformational transitions between functional states are among
questions that are particularly suited to be studied by single particle cryo-EM.
TRPV1 ion channel is polymodal nociceptor that integrates signals generated from a range of biochemical and
biophysical stimuli. It is biochemically well-behaved and physiologically and pharmacologically well characterized.
With various endogenous stimuli and natural exogenous compounds trapping the channel in various functional
states, we have determined structures of TRPV1 in various stable conformations. In the next step, we will use
TRPV1 as a model system to exploit using novel cryo-EM advances to probe the range of conformational states
sampled by this complex signal integrator. For many other TRP channels, in which there is no suitable
pharmacological tools to trap the channels in specific stable conformations, methods developed with the model
system can be used to study mechanisms of channel gating.

## Key facts

- **NIH application ID:** 10166355
- **Project number:** 1R35GM140847-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Yifan Cheng
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $321,844
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10166355

## Citation

> US National Institutes of Health, RePORTER application 10166355, Advancing cryo-EM technology to address difficult biological questions (1R35GM140847-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10166355. Licensed CC0.

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