Foundational Investigations into Bacterial Surface Glycan Dynamics

Project Abstract Bacteria have existed for millions of years and have evolved sophisticated methods of communication. One primary mechanism is through the glycans on their surface, which facilitate interactions between bacterial cells and enables their invasion into host cells. Obtaining a fundamental understanding of these glycan interactions offers an avenue to stop bacterial

invasions and develop new therapeutic interventions. By introducing advanced computational techniques, we will elucidate the multifaceted world of bacterial surface glycans, bridging the gaps in our current understanding and advancing new avenues in glycobiology research. These goals align with our lab’s mission of computationally modeling biological interfaces:

• Constructing In Silico Libraries of Bacterial Surface Glycans: Our goal is to develop a searchable and publicly available in silico glycan library. Within the first five years, we will focus on amino sugars and essential bacterial surface glycans, including LPS serotypes, tailored for docking studies designed for both computational and experimental researchers.

Beyond five years, we will continuously update and add to this library including peptidoglycans and o-linked glycans. • Elucidating the Foundations of Glycan-Collectin Dynamics: Our goal is to create design rules for glycan-collectin dynamics setting the foundation for the "Collectin Designer" software tool.

Within the first five years, we will focus on modeling, analyzing, and assessing the interactions of bacterial surface glycans with two human collectins. Beyond five years, we will expand to the other four human collectins and continue adding to the design rules which will lead to the creation of the Collectin Designer software.

• Developing a Process to Optimize Bacterial Glycan Interactions with Collectins using SP-D Interaction with Pseudomonas aeruginosa (Pa) Glycans as a Model System: Our goal is to develop a process to optimize bacterial glycan interactions with collectins. Within the first five years, we will design a theoretical SP-D that binds more effectively to the LPS and pilin

structures of Pa. We will test the efficacy of binding through in vitro binding assays. Beyond five years, we will refine our SP-D model and test in vivo. The vision of this research program is to bring an integrated approach that synergizes computational tools and experimental validations, to deepen our foundational knowledge of

glycan-collectin interactions and their broader implications.