Description du projet
Caractériser le rôle des glycanes dans l’infection virale avec une résolution atomique
À l’image de duvet d’une pêche, toutes les cellules sont couvertes de glycanes de surface. Cette famille diversifiée de sucres macromoléculaires constitue une cible clé des virus, dont beaucoup adhèrent à la couche externe de glycanes pour entamer le processus d’infection d’une cellule. La caractérisation de ce processus est essentielle à la lutte contre les infections virales, mais elle constitue un véritable défi compte tenu de l’énorme complexité des glycanes, de leur synthèse, de leur structure chimique, de leur conformation et de leur dynamique. Le projet Glyco13Cell, financé par le CER, propose une approche radicale. L’équipe remodèlera chimiquement les glycanes directement à la surface des cellules tout en s’appuyant sur le marquage isotopique. Des sondes actives de résonance magnétique nucléaire feront alors la lumière sur les rôles des glycanes à une résolution atomique.
Objectif
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 a tremendous potential for combating infections. Elucidating the molecular basis of infection is essential, but far from trivial. The complexity of the chemistry of glycans, including synthesis, structure, conformation, and dynamics 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 in 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.
I propose an unprecedented strategy to untangle the key glycan’s molecular interaction features breaking the limits in answering fundamental questions related to sugar structure, presentation, dynamics, and eventually 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.
I am in a favoured position to accomplish this project due to my experience in NMR, synthesis, and mammalian cells manipulation. I will combine chemical biology tools, novel chemical and enzymatic synthesis, and NMR-based methods: From chemistry to biology and beyond.
Glyco13Cell will gap down the observed differences between in vitro and in vivo results paving the way for develop novel glycan-based tools for predicting, diagnosing and treating infectious diseases.
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 & proteoms towards personalized medicine.
Champ scientifique
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thème(s)
Régime de financement
HORIZON-ERC - HORIZON ERC GrantsInstitution d’accueil
48160 DERIO VIZCAYA
Espagne