# Function and Structure of Surface-bound Tau

> **NIH NIH R15** · VASSAR COLLEGE · 2020 · $367,500

## Abstract

PROJECT SUMMARY/ABSTRACT
The microtubule associated protein tau has a variety of important cellular functions, most
notably stabilizing and organizing microtubules in axons. Tau is also implicated in a host of
neurodegenerative disorders such as Pick’s disease, frontotemporal dementia, parkinsonism
linked to chromosome 17 and Alzheimer’s disease, which are all characterized by abnormal
aggregation of the protein into paired helical filaments and neurofibrillary tangles. Although tau
has been the focus of significant recent research, the full range of its normal functions are not
understood. Tau is an intrinsically disordered protein and its interactions with microtubules are
dynamic, so it has been especially difficult to study the structure of tau-bound to microtubules.
Thus, the overall goal of this project is to build a better understanding of tau’s behavior when it
is bound to microtubules, including changes in structure and function that precede pathological
aggregation. To achieve this end, this project will investigate the properties of tau when it is
bound to solid supports in physiologically-relevant conformations, applying an atomic force
microscopy (AFM) based assay that interrogates the protein at the nanoscale. Both AFM force
spectroscopy and imaging will be used in order to conduct physical-mechanical characterization
of normal tau and pro-aggregant mutants, and to examine heterogeneity in assemblies of the
protein.
This study focuses on three specific aims. The first aim is to characterize normal tau structure
and intermolecular interactions when it is surface-bound, studying the six naturally-occurring
isoforms of the protein. The second aim will investigate the properties of C-terminal truncated
tau mutants, in order to understand the role that the C-terminal plays in normal tau-tau
interactions, and to understand how C-terminal truncation promotes abnormal aggregation of
tau. In the third aim, tau variants with prevalence in disease will be studied to investigate the
origins of their changes in microtubule binding affinity, structure, and propensity for
pathological aggregation.

## Key facts

- **NIH application ID:** 9962995
- **Project number:** 1R15NS108245-01A1
- **Recipient organization:** VASSAR COLLEGE
- **Principal Investigator:** Zachary John Donhauser
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $367,500
- **Award type:** 1
- **Project period:** 2020-04-15 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962995

## Citation

> US National Institutes of Health, RePORTER application 9962995, Function and Structure of Surface-bound Tau (1R15NS108245-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9962995. Licensed CC0.

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