# Oxytocin Modulation of Social Behavior

> **NIH NIH K00** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $67,200

## Abstract

Project Summary/Abstract:
The Goal of this proposal is to dissect the mechanistic details surrounding the nucleation and early events
of tau aggregation. Tau is a key misfolding and aggregating protein associated with both Alzheimer’s disease
(AD) and frontotemporal dementia (FTD). There has been a significant increase in the number of people
suffering from neurodegenerative diseases, including AD and FTD and is expected to continue to rise as there
are currently no cures. While many studies have attributed the aggregation of tau as a cause of the disease, the
process of nucleation and self-prorogation of tau aggregation is not well understood. One major challenge has
been to determine the conformational basis of tau misfolding and aggregation due to the large size of the
protein. To address this challenge, minimal sequence of 31 residues has been defined as the conformational
nucleus responsible for the self-propagation of tau aggregation, thus providing a foundation for investigating the
early stage of nucleation. With this observation we hypothesize that residues within this minimal sequence
interact with other domains of the protein to induce aggregation at the single molecule level as well as interact
with other misfolded tau molecules to seed aggregation. To test this, we propose to map these interactions in a
site specific manner using minimally perturbing fluorescent unnatural amino acids to shed light on the early
non-fibrillar oligomer formation and the local conformational dynamics over the course of aggregation.
Innovation: In order to dissect site-specific interactions, kinetics and conformational dynamics surrounding the
nucleation and early aggregation events of tau, new tools are needed. Unnatural amino acids sensitive to
hydration are uniquely useful to probe aggregation because of the change in local hydration exhibited when
once soluble protein becomes insoluble during aggregation. Unfortunately, current technologies such as
fluorescent proteins and dyes are not ideal to study intramolecular events due to their prohibitive size. Unnatural
amino acids chromophores offer the desired spectroscopic qualities in a framework that is non-perturbing to
both structure and function of tau, making it ideal to study the intra- and intermolecular conformational
dynamics, kinetics and interactions during tau aggregation. Together this will inform our direct knowledge to
help elucidate the aggregation pathway.

## Key facts

- **NIH application ID:** 10044651
- **Project number:** 8K00MH123667-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Ismail A. Ahmed
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $67,200
- **Award type:** 8
- **Project period:** 2019-12-02 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10044651

## Citation

> US National Institutes of Health, RePORTER application 10044651, Oxytocin Modulation of Social Behavior (8K00MH123667-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10044651. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*