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Molecules Inhibiting Translation in Cancer cells

Project description

Translation inhibition in cancer cells

Understanding the precise regulation of translation to design inhibiting drug candidates is a very complicated task that requires a high level of accuracy and modern techniques. Y box binding protein 1 (YB-1), a major mRNA binding protein and a master regulator of translation in cancer cells, has been considered as a therapeutic target for the treatment of drug-resistant cancer. However, no small molecules with high affinity and specificity against YB-1 have been proposed so far, and the structural data essential to test drug relevance are missing. The EU-funded MITiC project will focus on studying the inhibition mechanism of YB-1 to design anti-cancer drugs able to overcome resistance, using computational and experimental data and combining them with data mining techniques.

Objective

YB-1 is one of the major mRNA binding proteins and a master regulator of translation in cancer cells. It has been recently considered as a therapeutic target for the treatment of cancer and drug-resistant cancer. However, no small molecules with high affinity and specificity against YB-1 have been proposed so far, and the structural data essential to interrogate their relevance are missing. Understanding the function of translation regulation systems in order to design drug candidates is a very delicate procedure that requires a high level of accuracy and state-of-the-art techniques. Based on a promising preliminary finding of an active compound, we will focus in depth on studying the inhibition mechanism of YB-1 in order to help design new anti-cancer drugs able to overcome drug resistance. The research approach developed in this context aims to use in synergy advanced computational and experimental techniques while overcoming all limitations in a concerted way. This work is concerned with providing a sufficiently accurate computational model that is computationally efficient, specific experimental data and combining them with data mining techniques, for a molecular-level characterization of the inhibition dynamics and thermodynamics. This project is based on a multidisciplinary approach that requires knowledge of biology, biochemistry, physical chemistry, theoretical chemistry and bioinformatics in order to contribute to the medicine of the future.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

(opens in new window) H2020-MSCA-IF-2019

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Coordinator

UNIVERSITE D'EVRY-VAL D'ESSONE
Net EU contribution
€ 184 707,84
Address
BOULEVARD FRANCOIS MITTERAND 23
91025 EVRY
France
Region
Ile-de-France Ile-de-France Paris
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 184 707,84