Descrizione del progetto
Applicare il resveratrolo bioingegnerizzato a nuovi schemi di terapia antitumorale
Il resveratrolo è un polifenolo naturale di origine vegetale che agisce contro gli agenti patogeni, compresi batteri e funghi. Finanziato dal programma di azioni Marie Skłodowska-Curie, il progetto p53-REACT si propone di ingegnerizzare un ospite batterico per produrre varianti del metabolita del resveratrolo e studiare la loro interazione con la proteina p53, un soppressore tumorale. L’obiettivo è quello di chiarire la modalità d’azione delle molecole di resveratrolo sui mutanti p53, concentrando l’attenzione su nuovi schemi terapici tumorali. Il progetto rappresenta un ampio studio dei derivati del resveratrolo che agiscono come inibitori dell’aggregazione di p53 e coinvolge risorse computazionali all’avanguardia, nonché bioingegneria metabolica e strutturale.
Obiettivo
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.
Campo scientifico
- engineering and technologyindustrial biotechnologymetabolic engineering
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesclinical medicineoncology
- medical and health sciencesbasic medicinepathology
- natural sciencesbiological sciencesmolecular biologystructural biology
Parole chiave
Programma(i)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Meccanismo di finanziamento
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinatore
80333 Muenchen
Germania