# Project 4: Novel reagent development to enable molecular characterization

> **NIH NIH U19** · UNIVERSITY OF WASHINGTON · 2021 · $455,358

## Abstract

Abstract
Project 4 will test the hypothesis that computationally designed protein “minibinders” and logic-gated switches
targeting cerebrospinal fluid (CSF) protein biomarkers and protein particles can serve as versatile capture and
detection agents to vastly improve the molecular characterization of CSF samples. The availability of these
reagents should support the overall U19 goal of improving our understanding of CSF biomarkers as direct
measures of age-related cognitive decline and Alzheimer's Disease (AD) pathophysiology.
We have integrated our work plan within the highly focused U19 Project: Next Generation Translational
Proteomics for Alzheimer's and Related Dementias to test the above hypothesis. In collaboration with Projects
1–3, our main goal is to develop an optimized set of computationally designed minibinders (hyperstable binding
proteins of length <65 aa) as CSF protein biomarker capture agents, and ultra-specific logic-gated reagents for
detection of CSF particles that have two defined protein components.
The research will iterate between computational design and experimental testing, with feedback at each stage
from CSF assay experiments conducted in collaboration with Projects 1-3 which will guide improvement of the
minibinder design methods for capture of specified CSF biomarker protein targets, and for ultra-specific logic-
gated detection of CSF particles with two composite protein components. The outcomes will be (i) specific CSF
biomarker capture and detection systems for AD and other age-related neurodegenerative disorders, and (ii)
an integrated computational-experimental pipeline for rapid on demand engineering of new protein based
diagnostic agents for neurodegenerative disorders in general. Therefore, Project 4 relies on a close
collaboration with Projects 1-3 and Cores 1-4 within the highly interactive U19 program.

## Key facts

- **NIH application ID:** 10105266
- **Project number:** 5U19AG065156-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** DAVID BAKER
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $455,358
- **Award type:** 5
- **Project period:** 2020-02-15 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10105266

## Citation

> US National Institutes of Health, RePORTER application 10105266, Project 4: Novel reagent development to enable molecular characterization (5U19AG065156-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10105266. Licensed CC0.

---

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