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

Project description

Application of bioengineered resveratrol in new anticancer therapy concepts

Resveratrol is a natural polyphenol of plant origin that acts against pathogens, including bacteria and fungi. Funded by the Marie Skłodowska-Curie Actions programme, the p53-REACT project aims to engineer a bacterial host to produce resveratrol metabolite variants and study their interaction with the tumour suppressor protein p53. The objective is to elucidate the mode of action of resveratrol molecules on the p53 mutants with a focus on new concepts for cancer therapy. The project represents a broad study of the resveratrol derivatives acting as p53 aggregation inhibitors and involves cutting-edge computational resources and metabolic and structural bioengineering.

Objective

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.

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Topic(s)

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2021-PF-01

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Coordinator

TECHNISCHE UNIVERSITAET MUENCHEN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 189 687,36
Address
Arcisstrasse 21
80333 Muenchen
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost

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