# Tools for manipulating protein condensates at the synapse

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2023 · $429,000

## Abstract

Diverse neural functions are driven by concentrated biomolecular assemblies known as condensates. For
example, the postsynaptic density, a structure that anchors neurotransmitter receptors and signaling molecules
at the synapse, is thought to form a condensate through a phase-separation process involving multiple highly-
networked scaffold molecules. How do the biophysical and material properties of the postsynaptic condensate
contribute to synaptic function and plasticity? This project will develop and extend methods that allow inducible
formation and/or disruption of biomolecular condensates, applying them in neurons to modulate the material
properties of the postsynaptic density while simultaneously assessing synapse structure and function. Aim 1
will develop and apply tools to rapidly increase the rigidity of the postsynaptic density and assess the functional
consequences on synaptic structure and plasticity. Aim 2 will focus on methods to inducibly increase the fluidity
of the postsynaptic density, reducing the valency of specific scaffold molecules involved in condensate
formation. This work will develop general-use tools for manipulating biomolecular condensates throughout the
nervous system, with implications for neuronal development, neuropsychiatric diseases, addiction and other
brain disorders.

## Key facts

- **NIH application ID:** 10725576
- **Project number:** 1R21MH134019-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Matthew J Kennedy
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $429,000
- **Award type:** 1
- **Project period:** 2023-08-15 → 2025-08-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10725576

## Citation

> US National Institutes of Health, RePORTER application 10725576, Tools for manipulating protein condensates at the synapse (1R21MH134019-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10725576. Licensed CC0.

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