# Investigation of the Effect of Structural Modifications of Tau on Assembly State and Seeding

> **NIH NIH RF1** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $137,112

## Abstract

Abstract (from parent application)
Despite significant progress in Alzheimer’s disease (AD) in general and tau pathobiology in particular, there is
still no effective treatment or prevention for AD or any other tauopathy. To develop such therapy, detailed
knowledge of the structural biology and structure–activity relationship of tau is needed, including the way
sequence alterations and post-translational modifications affect tau self-assembly into toxic oligomers and
aggregates, and how these parameters impact tau seeding and toxicity. Here, we propose a systematic, detailed
study of these aspects of tau pathology taking advantage of recent developments in mass-spectrometric,
biochemical, and cell biology methods. We will study the effect of primary-structure alterations and post-
translational modifications on tau oligomerization and aggregation in vitro and compare recombinant and in-vivo
generated tau. We will then examine how all of these factors affect tau seeding using a recently developed highly
sensitive biosensor cell line. To advance therapy development, we will also test the effect of assembly
modulators on tau self-assembly and seeding. A unique aspect of the project is the combination of expertise of
the PI and Co-I groups, which will allow obtaining insight into the structure–activity relationship of tau on multiple
levels and answering currently pending questions about the complex processes governing this crucial aspect of
AD.

## Key facts

- **NIH application ID:** 10241797
- **Project number:** 3RF1AG054000-01A1S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** GAL BITAN
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $137,112
- **Award type:** 3
- **Project period:** 2017-07-15 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241797

## Citation

> US National Institutes of Health, RePORTER application 10241797, Investigation of the Effect of Structural Modifications of Tau on Assembly State and Seeding (3RF1AG054000-01A1S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10241797. Licensed CC0.

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