# Evolution of new protein function in the multi-protein, multi-functional Toll-like receptor 4 complex

> **NIH NIH R01** · UNIVERSITY OF OREGON · 2024 · $100,325

## Abstract

Project summary
We propose purchasing a High-Performance Liquid Chromatography (HPLC) system to place
in-line with an existing multi-angle laser light scattering instrument in the Harms lab. This will
allow us to precisely characterize the oligomeric states of TLR4 (Toll-like receptor 4) and its
associated proteins. The overall goal of the funded parent project is to dissect the evolution of
the TLR4 protein complexes over the last 400 million years. TLR4 is an important driver for
inflammation in both healthy contexts (e.g, response to infection, wound healing) and
pathological cancers (e.g., chronic inflammation, cancer). It interacts with multiple protein
partners as part of these functions, including MD-2, CD14, and S100A9. To understand the
evolution and mechanism by which the TLR4 complex has its effects, we need sharp tools to
dissect the interactions between these proteins.
All three aims of the parent project will benefit from the requested instrumentation. The first
two aims require understanding how TLR4 binds to different agonist molecules and
oligomerizes in response; the third aim looks the evolution of the key support molecule CD14,
which directly binds TLR4. The ability to directly measure protein-protein interactions and
oligomerization is critical to achieving these aims.

## Key facts

- **NIH application ID:** 11099510
- **Project number:** 3R01GM146114-03S1
- **Recipient organization:** UNIVERSITY OF OREGON
- **Principal Investigator:** Michael Jonathan Harms
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $100,325
- **Award type:** 3
- **Project period:** 2022-06-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11099510

## Citation

> US National Institutes of Health, RePORTER application 11099510, Evolution of new protein function in the multi-protein, multi-functional Toll-like receptor 4 complex (3R01GM146114-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11099510. Licensed CC0.

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