Descripción del proyecto
Caracterización atómica del papel de los polisacáridos en la infección vírica
Los polisacáridos recubren la superficie de las células de forma parecida a la pelusa de un melocotón. Esta diversa familia hidratos de carbono macromoleculares constituye la diana de muchos virus, que se adhieren a esta capa externa de polisacáridos de las células para iniciar el proceso de infección. Caracterizar este proceso es fundamental para combatir las infecciones víricas, pero es bastante difícil debido a la gran complejidad de la síntesis, la estructura química, la conformación y la dinámica de los polisacáridos. El proyecto Glyco13Cell, financiado por el Consejo Europeo de Investigación, propone un enfoque revolucionario. Su equipo reconfigurará químicamente los polisacáridos en la superficie celular mediante el marcaje isotópico. A continuación, sondas activas de resonancia magnética nuclear iluminarán las funciones de los polisacáridos con resolución atómica.
Objetivo
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.
Ámbito científico
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
HORIZON-ERC - HORIZON ERC GrantsInstitución de acogida
48160 DERIO VIZCAYA
España