# Synthetic mucins in epithelial models to probe virus-mucin interactions

> **NIH NIH R35** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $107,800

## Abstract

PROJECT SUMMARY
Mucin glycoproteins are the essential component of mucus and the epithelial cellular glycocalyx. Mucins are
essential for life in creatures from jellyfish to humans and play roles in hydration, lubrication, nutrient absorption,
and host defense against pathogens. Mucin glycosylation is regulated by complex enzymatic pathways subject
to flux, resulting in heterogeneous and variable glycan patterns that vary between tissues and species, and that
evolve in response to diet and disease. The Kramer Lab is developing synthetic mucins, or synMUCs, that
harness the chemical and biophysical properties of native mucins but have molecularly tunable structures.
Polymerization of glycosylated amino acid N-carboxyanhydrides affords high molecular weight polypeptides with
the native peptide and glycan linkages. Compared to short peptides, polysaccharides, or traditional polymers
bearing attached sugars, synMUCs are the most authentic mucin mimics to date. The synMUCs will be applied
in engineered models of the glycocalyx and secreted mucus. These models will find broad future application in
studies of epithelial biology with application in cancer, drug delivery, immunity, and infection. Since mucins are
on the front lines of cellular defense, diverse viruses have evolved strategies to adhere to their glycans, alter
them, and even use them to enter host cells for replication. Virus-mucin binding can have outcomes on viral
diffusion, tissue specificity, and replication but molecular details are lacking due to mucin heterogeneity. We will
chemoenzymatically modify our synMUCs to display virus-binding sialic acid glycans. Viral binding preferences
for various sialic acid structures in different densities and from varied peptide backbone compositions will be
defined. The sialic-acid-bearing-synMUCs will be utilized to probe how mucins in the glycocalyx vs mucus
regulate adhesion, cell entry and replication, tissue tropism and viral gene evolution. This knowledge will shed
light on fundamental aspects of the viral life cycle and may assist in improving human health though development
of new antiviral therapeutics and disease transmission prevention strategies. Additionally, scientific citizenship
and mentoring are a priority and active involvement in supporting equity, diversity and inclusion of
underrepresented groups in STEM will be a focus for the duration of the project and beyond.

## Key facts

- **NIH application ID:** 11044912
- **Project number:** 3R35GM147262-03S1
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Jessica Kramer
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $107,800
- **Award type:** 3
- **Project period:** 2022-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11044912

## Citation

> US National Institutes of Health, RePORTER application 11044912, Synthetic mucins in epithelial models to probe virus-mucin interactions (3R35GM147262-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11044912. Licensed CC0.

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