NIH grant: Defining the Rules of Engagement: The Biophysical Basis of Protein-Glycan Interactions (1R35GM165947-01)

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NIH grant 1R35GM165947-01: Defining the Rules of Engagement: The Biophysical Basis of Protein-Glycan Interactions
Institute: {'code': 'GM', 'abbreviation': 'NIGMS', 'name': 'National Institute of General Medical Sciences', 'admin_org_id': '12500024', 'admin_funding_url': ''}. PI: Alex Joseph Guseman. Award: $211433.
Start: 2026-08-01T00:00:00.
Project Summary
Glycans are essential biomolecules that play critical roles in biological processes such as
immune regulation, protein folding, and cell-cell adhesion. Aberrant glycan interactions have
been implicated in numerous diseases, including cancer, diabetes, and transplant rejection.
Despite their importance, the molecular details of protein-glycan interactions remain poorly
understood. The proposed research program will uncover the structural and biophysical
principles governing protein-glycan interactions and to explore how the glycan-rich glycocalyx
environment influences protein stability and function. The proposed research has three major
objectives: (1) Define the thermodynamic and structural basis of protein-glycan interactions at
the atomic level to reveal how proteins achieve specificity within heterogeneous glycan
populations. (2) Using phage display develop engineered lectins with precise glycan-binding
specificities and use them to understand the molecular grammar that governs glycan
recognition. Furthermore, the impact of this project will be broadened by using these engineered
lectins will as tools for studying chemically defined glycan structures/glycoforms in biology. (3)
Investigate how nonspecific interactions in the glycocalyx modulate protein stability and folding
dynamics. Using cutting-edge biophysical methods, including the development of new on-cell
nuclear magnetic resonance spectroscopy methods, Biolayer Interferometry, phage display and
others, this work will bridge critical knowledge gaps in the field of glycobiology. The results of
this research will advance our fundamental understanding of protein-glycan interactions and
their role in cellular environments. These findings have the potential to inform the development
of therapeutic approaches targeting glycan-mediated processes in health and disease.

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