# Dynamic Mechanisms of Membrane Channel Gating by CryoEM

> **NIH NIH R35** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $171,919

## Abstract

Project Summary
Pore-forming membrane channels are central mediators of many complex biological phenomena; such as
synchronizing the contraction of our heart and electro-chemical signals in our brain, and detecting light, sound,
touch, taste and smells of the world around us. This ability is dependent upon dynamic mechanism used to
spatially and temporally modulate their cellular activity. Our research group is focused on understanding how
these types of phenomena are choreographed by remarkably complex strategies of cell-to-cell communication,
through the gap junctions. We aim to develop a molecular and atomic-level of mechanistic understanding of
how gap junctions coordinate inter-cellular communication. To achieve this level of detail, we are combining
the unique power of electron cryo-microscopy (CryoEM), together with computational modeling and targeted
biophysical and functional studies to address several fundamental questions, such as: i) How do the gap
junctions selectively control the flow of chemical information between cells? ii) How are their activities
allosterically modulated by physiological signals and pharmacological agents? iii) How gap junction assembly,
structure and function is coupled with the local lipid/cellular environment? Despite their physiological and
medical relevance, membrane proteins still only represent ~4% of the protein structure database. However,
recent advances in the field of high-resolution CryoEM, coupled with advancements in membrane protein
biochemistry and in situ imaging technologies, are beginning to revolutionize the way we structurally
characterize these proteins. With these tools in hand, we are addressing several key questions about gap
junction assembly, selectivity and regulation. The results of our investigations are expected to provide an
architectural framework and the mechanistic knowledge required for the rational development of targeted
therapies against a range of gap junction related diseases, such as blindness, deafness, arrhythmia, stroke
and cancers.

## Key facts

- **NIH application ID:** 11035774
- **Project number:** 3R35GM124779-09S1
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Stephen Loen Reichow
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $171,919
- **Award type:** 3
- **Project period:** 2017-08-15 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11035774

## Citation

> US National Institutes of Health, RePORTER application 11035774, Dynamic Mechanisms of Membrane Channel Gating by CryoEM (3R35GM124779-09S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11035774. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*