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Dynamics of p53 mutant reactivation and the anti-carcinogenic action of engineered resveratrol analogues

Projektbeschreibung

Biotechnologisch hergestelltes Resveratrol für neue Krebstherapiekonzepte

Resveratrol ist ein natürliches Polyphenol pflanzlichen Ursprungs, das gegen Krankheitserreger, einschließlich Bakterien und Pilze, wirkt. Das über die Marie-Skłodowska-Curie-Maßnahmen finanzierte Projekt p53-REACT zielt darauf ab, einen bakteriellen Wirt so zu verändern, dass er Varianten von Resveratrol-Metaboliten produziert, und deren Wechselwirkung mit dem Tumorsuppressorprotein p53 zu untersuchen. Ziel ist es, die Wirkungsweise von Resveratrol-Molekülen auf die p53-Mutanten aufzuklären, um so neue Krebstherapiekonzepte auszuarbeiten. Das Projekt stellt eine breit angelegte Untersuchung der Resveratrol-Derivate dar, die als p53-Aggregationshemmer wirken, und umfasst modernste Rechenressourcen sowie metabolische und strukturelle Biotechnik.

Ziel

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.

Koordinator

TECHNISCHE UNIVERSITAET MUENCHEN
Netto-EU-Beitrag
€ 189 687,36
Adresse
Arcisstrasse 21
80333 Muenchen
Deutschland

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Aktivitätstyp
Higher or Secondary Education Establishments
Links
Gesamtkosten
Keine Daten

Partner (1)