# Phase Transition-Mediated Tau Function and Dysfunction

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $400,000

## Abstract

Project Summary
Phase Transition-Mediated Tau Function and Dysfunction
 The proposed research will decipher the molecular mechanism of liquid-liquid phase
separation (LLPS)-mediated Tau function and dysfunction. Phase-separated Tau droplets
enrich tubulin and facilitate microtubule assembly (Tau function), whereas persistent droplets
lead to protein aggregation.
 Utilizing prior extensive experience with disordered protein systems, the investigators will
determine how LLPS links Tau loss-of-function and gain-of-toxic dysfunction in three stages:
They will characterize how pathologic post-translational modifications (PTMs;
hyperphosphorylation and hyperacetylation) modulate Tau LLPS-mediated microtubule
assembly and protein aggregation (Aim 1); they will track Tau conformations that are key to both
LLPS-mediated Tau function and dysfunction (Aim 2); and, they will determine how co-
aggregating proteins initiate/ facilitate/ synergize Tau aggregation (Aim 3).
 The first Aim will utilize ensemble spectroscopy and time-lapse microscopy techniques
to understand the role of PTMs in LLPS-mediated function and dysfunction. Phase transition
maps of different Tau variants will be generated to characterize how different PTMs alter Tau
LLPS. Effects of Tau variant co-partitioning in droplets or fibrillar aggregates on Tau function
and dysfunction will also be studied.
 The second Aim will utilize ultrasensitive fluorescence spectroscopy techniques to track
conformational conversions as monomeric Tau forms condensed droplets and as liquid droplets
transform to solid states, i.e., functional (in microtubule assembled filaments) and/or
dysfunctional states (amyloid fibril states).
 The third Aim will determine the role of co-aggregating proteins in Tau LLPS and
subsequent protein aggregation. Synergistic interaction between co-phase separating proteins
will be characterized. Mechanism of aggregate cross-seeding will provide insights into protein
co-misfolding.

## Key facts

- **NIH application ID:** 9996811
- **Project number:** 5R01NS105874-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Allan Chris Ferreon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $400,000
- **Award type:** 5
- **Project period:** 2019-08-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9996811

## Citation

> US National Institutes of Health, RePORTER application 9996811, Phase Transition-Mediated Tau Function and Dysfunction (5R01NS105874-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9996811. Licensed CC0.

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