Descripción del proyecto
Aplicación del resveratrol creado por bioingeniería en nuevos conceptos terapéuticos contra el cáncer
El resveratrol es un polifenol natural de origen vegetal que actúa contra los agentes patógenos, incluidas las bacterias y los hongos. El objetivo del proyecto p53-REACT, financiado por las Acciones Marie Skłodowska-Curie, es diseñar un hospedador bacteriano que produzca variantes del metabolito del resveratrol y estudiar su interacción con la proteína supresora de tumores p53. El propósito es dilucidar el modo de acción de las moléculas de resveratrol sobre los mutantes de p53, con vistas a nuevos conceptos para el tratamiento antineoplásico. El proyecto representa un amplio estudio de los derivados del resveratrol que actúan como inhibidores de la agregación de p53 y conlleva el uso de recursos informáticos de vanguardia y bioingeniería metabólica y estructural.
Objetivo
The project proposal aims to engineer a bacterial host to produce variants of secondary metabolite resveratrol and address the interrelationship between dynamics, structure and function of a system of high medical interest, the tumor suppressor protein p53. The study considers to elucidate the mode of action of these molecules against the p53 mutants and work on new concepts for cancer therapy. Inside the cell, the folding of a protein is a fast and robust process. Sometimes, however, sudden changes in the balance between different existing forces result in incorrect folding of the peptide chain, which ends up generating amyloid aggregates within the cell that lead to the gain of toxic function, since these aggregates can conduct to death of the cell in question. Most amyloidogenic pathologies are neurodegenerative, however the aggregation also plays an important role in cancer. The project provides a broad framework for the study of the resveratrol derivatives acting as p53 aggregation inhibitors by using cutting-edge tools of computational resources, metabolic engineering and structural biology. But could, in principal, be applied to exploit the chemical diversity of other biocompounds similarly intending to act as less cytotoxic agents in a more effective antineoplastic therapy, which represents one of the major existing scientific gaps. It is a proposal on a very important topic that will be studied from a unique perspective.
Ámbito científico
- engineering and technologyindustrial biotechnologymetabolic engineering
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesclinical medicineoncology
- medical and health sciencesbasic medicinepathology
- natural sciencesbiological sciencesmolecular biologystructural biology
Palabras clave
Programa(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Régimen de financiación
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinador
80333 Muenchen
Alemania