Isotopically labelling of cell surface glycans to illuminate infectious processes at atomic resolution

Introduction

Every human cell is covered by a dense coat of glycans (sugars, carbohydrates). Sugars are the first molecules that viruses encounter when they approach host cells. Many viruses encode lectins to adhere to the outer glycan layer and start infection. In this scenario, Glycoscience holds tremendous potential for combating infections.

Challenges in Glycoscience

Elucidating the molecular basis of infection is essential, but far from trivial. The complexity of the chemistry of glycans, including:

• Synthesis
• Structure
• Conformation
• Dynamics

This complexity hampers the full knowledge of sugar-mediated recognition events and the development of glycan-based drugs. Surfing the current information on glycan/lectin interactions, we stumble upon contradictory outcomes, pointing out the tremendous difficulty of translating in vitro results to the in vivo environment, which limits the translation from the bench to clinics.

Proposed Strategy

I propose an unprecedented strategy to untangle the key glycan’s molecular interaction features, breaking the limits in answering fundamental questions related to:

1. Sugar structure
2. Presentation
3. Dynamics
4. Function

I will chemically remodel the glycans directly on the cell surface, using NMR active probes to decode their roles at atomic resolution while preserving their presentation in a near-to-in-vivo environment.

Personal Qualifications

I am in a favored position to accomplish this project due to my experience in:

• NMR
• Synthesis
• Mammalian cell manipulation

I will combine chemical biology tools, novel chemical and enzymatic synthesis, and NMR-based methods: From chemistry to biology and beyond.

Impact of Glyco13Cell

Glyco13Cell will bridge the observed differences between in vitro and in vivo results, paving the way for developing novel glycan-based tools for predicting, diagnosing, and treating infectious diseases.

Conclusion

Now it’s time. The increasing understanding of infection biology with the atomic precision of modern chemical tools will make glycomics run in parallel with genomics and proteomics towards personalized medicine.