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The Shape of Escape: Decoding the Structural Effects and Evolutionary Trajectories Involving N-Glycosylation in Influenza A Hemagglutinin

Award Number: F31AI200275
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/04/2026
PERIOD OF PERFORMANCE END DATE: 12/03/2027

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The Shape of Escape: Decoding the Structural Effects and Evolutionary Trajectories Involving N-Glycosylation in Influenza A Hemagglutinin - Project Summary Influenza A virus (IAV) remains a formidable threat to global health due to its high mutation rate and capacity for immune evasion, which challenge the effectiveness of seasonal vaccines and limit our ability to anticipate emerging strains. A major contributor to this immune escape is N-glycosylation site emergence (NSE) on hemagglutinin (HA), which can shield key regions from the host immune response. However, we currently lack a predictive framework to forecast when, where, and why these glycosylation events arise. This proposed work addresses that critical knowledge gap by integrating codon-level mutational probabilities, structural modeling, and molecular dynamics simulations to uncover the genetic and biophysical rules governing NSE emergence and their impact on viral evolution. In Aim 1, I will analyze HA sequences from H1N1 and H3N2 strains to define the common route by which mutations give rise to NSEs and assess their structural positioning and immune relevance. I will utilize established methods to determine IAV strain NSE genotype accessibility and trace the mutational trajectories that give rise to NSE motifs. Additionally, I will evaluate the structural positioning and epitope coverage of rare, common, and hypothetical glycosylation events using predicted, glycosylated HA structures. In Aim 2, I will perform molecular dynamics simulations of key historical NSE events in human-circulating H1N1 and H3N2 IAV populations to evaluate how N-glycan shielding alters HA surface accessibility and reshapes local evolutionary trajectories. These simulations will illuminate how glycans influence residue conservation, epitope exposure, and future mutational potential. Together, these aims will pave the groundwork for a rigorous, mechanistic method for forecasting immune escape in IAV, enhancing our ability to identify high-risk strains in real time and informing vaccine strain selection. The proposed work leverages cutting-edge computational tools and a novel evolutionary lens to address a longstanding challenge in influenza biology, with broad implications for anticipating viral adaptation in other rapidly evolving pathogens.


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 = $49,114 )
2026	2026	ST. JUDE CHILDREN'S RESEARCH HOSPITAL GRADUATE SCHOOL OF BIOMEDICAL SCIENCES, LLC	262 DANNY THOMAS PL # 1500	MEMPHIS	TN	38105	SHELBY	USA	Allergy and Infectious Diseases Research	000	1	6/9/2026	NEW	$49,114
														Subtotal = $49,114

Grand Total All Awards = $49,114

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The Shape of Escape: Decoding the Structural Effects and Evolutionary Trajectories Involving N-Glycosylation in Influenza A Hemagglutinin

Award Number: F31AI200275

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/04/2026

PERIOD OF PERFORMANCE END DATE: 12/03/2027

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