Description du projet
Appliquer le resvératrol issu de la bio-ingénierie à de nouveaux concepts de traitements anticancéreux
Le resvératrol est un polyphénol naturel d’origine végétale qui agit contre les agents pathogènes, notamment les bactéries et les champignons. Financé par le programme Actions Marie Skłodowska-Curie, le projet p53-REACT entend concevoir un hôte bactérien pour produire des variantes de métabolites de resvératrol, puis étudier leur interaction avec la protéine suppresseur de tumeurs p53. L’objectif est de comprendre le mode d’action des molécules de resvératrol sur les mutants de la protéine p53, en mettant l’accent sur de nouveaux concepts thérapeutiques pour soigner les cancers. Ce projet repose sur une vaste étude des dérivés du resvératrol agissant comme inhibiteurs de l’agrégation de la protéine p53, il s’appuiera sur des ressources informatiques de pointe et la bio-ingénierie métabolique et structurelle.
Objectif
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.
Champ scientifique
- engineering and technologyindustrial biotechnologymetabolic engineering
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesclinical medicineoncology
- medical and health sciencesbasic medicinepathology
- natural sciencesbiological sciencesmolecular biologystructural biology
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Régime de financement
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinateur
80333 Muenchen
Allemagne