# Equipment Supplement: Spatial Photoproximity Profiling of Dynamic Protein Complexes

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2024 · $205,848

## Abstract

Project Summary
The ability to sense dynamic changes in the cellular microenvironment and translate that information into rewired
biomolecular interactions forms the backbone of cellular signal transduction. Despite significant interest and
investment in methods capable of detecting and quantifying protein-protein and other protein-biomolecule
interactions, the most commonly employed methods solely map interaction in non-physiologic environments
outside of cells where many important factors contributing to the interactions under study are lost. These methods
are particularly poorly suited to study signaling events in cells that rely on the cellular architecture and chemical
environment in order to form and function. Therefore, new methods are needed to quantitatively map protein
“social networks” inside of living systems. Here we propose to develop and validate several complementary light-
dependent proximity profiling platforms capable of detecting protein interaction dynamics in live cells with high
spatial and temporal resolution, as well as minimal perturbation to the cellular environment. We will accomplish
this goal through three interconnected aims that are supported by preliminary data and our previously published
work with an intracellular photoproximity profiling platform. First, we will synthesize and test tunable
photoproximity chemical probes to map protein complexes at nanometer scale inside of cells. In parallel, we
propose to test potentially more efficient catalytic photoproximity profiling platforms for increased resolution of
low abundance macromolecular complexes inside of cells. Finally, we propose to apply these platforms to study
the dynamic sensing of altered metabolic and redox stress inside cells through the integrated antioxidant and
unfolded protein response pathways. These proximity profiles will enable drafting of the first quantitative,
comprehensive maps of the integrated stress response in cells, which will identify points of intervention for
diseases such as cancer, aging, and neurodegenerative disorders. Furthermore, the methods and proximity
profiles developed herein will also be widely useful to the biological community for application to diverse
questions in intracellular signal transduction.

## Key facts

- **NIH application ID:** 11037193
- **Project number:** 3R01GM145852-02S1
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Raymond E Moellering
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $205,848
- **Award type:** 3
- **Project period:** 2022-09-21 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11037193

## Citation

> US National Institutes of Health, RePORTER application 11037193, Equipment Supplement: Spatial Photoproximity Profiling of Dynamic Protein Complexes (3R01GM145852-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11037193. Licensed CC0.

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