Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Glycocalyx Remodeling as a Molecular Switch for Viral Entry

Award Number: DP2AI200969
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/11/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2031

Group Awards By:

View Award Description

Glycocalyx Remodeling as a Molecular Switch for Viral Entry - PROJECT SUMMARY Influenza A viruses (IAV) remain a persistent pandemic threat, underscoring the need for novel antiviral strategies. The polarized, mucin-rich epithelial glycocalyx serves as the first barrier to IAV infection by providing both decoy receptors and a steric barrier to IAV binding. Conflicting reports that mucins both inhibit and enhance IAV interactions reveal a mechanistic gap in how the glycocalyx serves its role as a barrier to IAV infection. I propose that an understanding of endogenous crosslinking within the epithelial glycocalyx will reconcile this paradox. Galectins are multi-valent, promiscuous, low-affinity sugar-binding proteins that crosslink glycans. Galectin-dependent crosslinking has recently been shown to modulate mucin thickness, a parameter known to influence IAV binding; however, investigations into the role of galectins in organizing mucins to prevent IAV infection have been limited. Furthermore, the glycocalyx is inextricably linked to the underlying plasma membrane. Galectin crosslinking has also been implicated in plasma membrane organization – inducing the formation of lipid domains and driving the formation of plasma membrane shapes, such as those required for endocytosis. Viral proteins tune the galectin affinity to glycans, and therefore reorganize galectin crosslinking. The central theme of this proposal is that viral neuraminidase (NA) remodels the glycocalyx to expose galectin ligands, thereby rewiring the physical organization of the glycocalyx to bypass its native barrier function and facilitate IAV entry. In Aim 1, I will define how galectin crosslinking tunes the mucin steric barrier. Using model membranes and established, off-the-shelf viral binding/entry assays on epithelial cells, I will test the hypothesis that the extent of galectin crosslinking of the glycocalyx will determine the biophysical properties of the mucin steric barrier, and that viral NAs will modulate these properties by desialylating mucins to facilitate binding and endocytosis. In Aim 2, I will investigate how glycocalyx remodeling influences the stability of lipid domains and the generation of membrane curvature. I will test the hypothesis that the sialylation state of mucins acts as a switch: highly sialylated mucins destabilize lipid domains and favor outward curvature, whereas desialylation enables galectin crosslinking, which stabilizes domains and drives invaginations. In Aim 3, I will resolve the endocytic route(s) used by IAV and the role of NA activity in those routes. Using high-resolution imaging, I will test the hypothesis that viral NA activity exposes galectin ligands on mucins and glycolipids, which in turn nucleate the formation of clathrin-independent carriers to facilitate viral internalization. The successful execution of this research will address major open questions about how the glycocalyx and lipid nanodomains coordinate to control plasma membrane morphology and biophysical properties, thereby blocking IAV infection. This NIAID DP2 support will accelerate these paradigm-shifting discoveries in IAV host–pathogen interactions and inspire novel antiviral strategies, while also developing a mechanistic framework that is broadly applicable to other pathogens that bind to the epithelial glycocalyx.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $429,586 )
2026	2026	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Allergy and Infectious Diseases Research	000	1	8/11/2026	NEW	$429,586
														Subtotal = $429,586

Grand Total All Awards = $429,586

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Glycocalyx Remodeling as a Molecular Switch for Viral Entry

Award Number: DP2AI200969

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/11/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2031

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer