# A droplet microfluidics approach to measuring protein aggregation

> **NIH NIH R21** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $202,500

## Abstract

Protein aggregation plays an important role in biology and disease. For example, a variety of syndromes
termed amyloid diseases involve the self-assembly of proteins into elongated amyloid fibers. A critical first step
in understanding the forces that underlie these processes is to define which proteins can self-associate – more
specifically, to identify the sequence determinants of aggregation. This is not feasible with current methods,
which are low-throughput and can only be used to study a very limited number of sequences. Furthermore,
isolating the contribution of protein sequence independent from the surrounding cellular milieu requires
measurement in biochemically defined conditions. We propose to develop a droplet microfluidics-based assay
to measure protein aggregation. Droplet microfluidics is a technique that generates and manipulates picoliter-
sized aqueous droplets, embedded in a stream of fluorinated oil that effectively isolates the droplets from one
another. These droplets can be generated at a rate of up to 5000 hertz, and individual genes can be
encapsulated in them, enabling the analysis of large libraries. We describe an approach to observe protein
self-assembly in droplets and to sequence the genes that give rise to aggregation-prone peptides. We will
apply this approach to two sequence libraries comprising variants of the Alzheimer’s associated protein, Tau. If
successful, this system could be applied to identify other sequences that self-associate, or sequences or
cofactors that modulate amyloid formation in a large variety of disease-associated proteins, as well as in other
sorts of aggregation phenomena such as liquid-liquid phase separation.

## Key facts

- **NIH application ID:** 9905475
- **Project number:** 5R21AG062874-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** MARC I DIAMOND
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $202,500
- **Award type:** 5
- **Project period:** 2019-04-15 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9905475

## Citation

> US National Institutes of Health, RePORTER application 9905475, A droplet microfluidics approach to measuring protein aggregation (5R21AG062874-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9905475. Licensed CC0.

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