# Dynamic Mechanisms of Membrane Channel Gating by CryoEM

> **NIH NIH R35** · PORTLAND STATE UNIVERSITY · 2021 · $371,250

## 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 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
cues? iii) How are cell-signaling platforms used to effectively control channel activity in a native multi-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 single particle
CryoEM, coupled with advancements in membrane protein biochemistry, are beginning to revolutionize the
way we structurally characterize these proteins. With these technological tools in hand, we are addressing
several key questions about gap junction selectivity and regulation. The results of our investigations are
expected to provide an architectural framework and the mechanistic knowledge required for the 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:** 10244881
- **Project number:** 5R35GM124779-05
- **Recipient organization:** PORTLAND STATE UNIVERSITY
- **Principal Investigator:** Stephen Loen Reichow
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $371,250
- **Award type:** 5
- **Project period:** 2017-08-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10244881

## Citation

> US National Institutes of Health, RePORTER application 10244881, Dynamic Mechanisms of Membrane Channel Gating by CryoEM (5R35GM124779-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10244881. Licensed CC0.

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