# Developing glycan-directed tools to investigate microbial infection

> **NIH NIH F32** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2022 · $39,423

## Abstract

7. Project Summary/Abstract
Glycans and glycoconjugates coating the surface of bacteria underscore critical roles in various biological
processes. One such process, which currently lacks mechanistic knowledge, is the interaction of the N-linked
heptasaccharide from enteric pathogen Campylobacter jejuni with host cell receptors, resulting in human
infection. N- and O-glycosylation systems in other pathogenic bacteria have shown similar essential interactions
to maintain virulence. Therefore, understanding these glycan-receptor interactions will provide information on
the molecular mechanisms behind microbial infection and reveal insights for future therapeutic intervention.
Current biochemical tools lack appropriate characteristics to study host-pathogen interactions, and there is a
resulting demand for the development of glycan-directed tools which can be leveraged to elucidate critical
molecular determinants of pathogenesis. The proposed project focuses on the generation of unique biochemical
species to understand the role of N-glycosylation in C. jejuni infection. Specifically, these include glycan-
decorated magnetic beads, multivalent glycan-functionalized peptides and glycan-specific protein binders. The
two multivalent glycan scaffolds will be attained through bioconjugate chemistries and chemoenzymatic
synthesis and the resulting chemically-defined scaffolds can afford specific protein binders through a yeast
surface display directed evolution. All three species will be applied in a microphysiological gastrointestinal model
(GutChip) of C. jejuni infection to afford pathogenic mechanistic information.
Glycan-coated magnetic beads interact with host cell receptors, allowing for the elucidation of the specific protein
which binds glycans. Multivalent glycan-functionalized polymers of heptasaccharide fragments can compete for
host cell receptors, providing information on the C. jejuni glycan regions involved in pathogenesis. The evolved
protein binders may mask the exposed N-glycan, thwarting glycan-mediated infectious mechanisms. The
lessons learned from the C. jejuni model will be broadly-applicable to other bacterial threats and therefore
invaluable to the glyco- and microbiology communities.
This project will be performed under the sponsorship of Professor Barbara Imperiali, in the Departments of
Biology and Chemistry at Massachusetts Institute of Technologies. Her support, the lab’s expertise, and the
wealth of resources available at MIT will allow for the successful completion of the proposed research project.

## Key facts

- **NIH application ID:** 10554883
- **Project number:** 3F32GM137477-02S1
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Megan E Kizer
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $39,423
- **Award type:** 3
- **Project period:** 2020-04-01 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10554883

## Citation

> US National Institutes of Health, RePORTER application 10554883, Developing glycan-directed tools to investigate microbial infection (3F32GM137477-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10554883. Licensed CC0.

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