# Fluorescence stereo microscopy for exploring the three-dimensional dynamics of receptor ligand interactions

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $72,135

## Abstract

1 This MIRA project will advance understanding of the function of tyrosine sulfation, a fundamental
 2 modification that regulates diverse biological functions. For example, sulfation plays a critical role
 3 in entry of HIV into human cells, in the interaction of microbial molecules with host immune
 4 receptors and in the activity of tick-derived peptides, which hold potential for treatment of blood
 5 clotting associated with cardiovascular diseases. Despite the increasing awareness of the
 6 importance of tyrosine sulfation, most sulfated peptide complexes have not yet been fully
 7 characterized. Further, we have only a partial view of the components essential for transducing
 8 the response of such activated complexes. We also have limited strategies for efficiently
 9 producing and testing the therapeutic potential of sulfated molecules. The PI is well positioned to
10 address these challenges. With support from the NIH, the PI discovered the host XA21 immune
11 receptor, a protein that is representative of a large class of plant and animal receptors. Further,
12 the PI’s team isolated and characterized a sulfated peptide secreted by a Gram-negative
13 bacterium that binds to the XA21 receptor and activates the immune response. We propose
14 research in three related areas: We will isolate and characterize the diversity of receptors that
15 bind sTyr peptides, identify and analyze sTyr binding interfaces and pioneer a strategy to produce
16 novel sulfated molecules in an efficient manner. To accomplish our goals, we will employ new
17 experimental tools and approaches. These include use of established whole genome sequenced
18 mutant lines to rapidly assess phenotypes of newly discovered genes, sensitive assays to assess
19 ligand binding, state-of-the-art mass yeast cell surface display and spectrometry approaches to
20 engineer receptors and identify key components of immune complexes. The knowledge gained
21 from this research will provide new insights into an essential biological process, laying the
22 foundation for the development of reagents capable of inhibiting or activating cellular interactions
23 with a high degree of affinity and specificity with potential applications in research, agriculture and
24 medicine.

## Key facts

- **NIH application ID:** 11100935
- **Project number:** 3R35GM148173-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** PAMELA C RONALD
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $72,135
- **Award type:** 3
- **Project period:** 2023-02-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11100935

## Citation

> US National Institutes of Health, RePORTER application 11100935, Fluorescence stereo microscopy for exploring the three-dimensional dynamics of receptor ligand interactions (3R35GM148173-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11100935. Licensed CC0.

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