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Computational design of proteins binding nucleosomal DNA with specificity for therapeutic applications

Objective

DNA compresses in the cell by forming nucleosome particles, which diminish the accessibility of transcription factors to DNA and provide fine regulatory mechanisms for gene expression and replication. Some proteins can still bind the exposed face of nucleosomal DNA and are known to promote cancer or viral infection, and strategies to block such binding events are promising for developing new epigenetic-like therapies. However, structural information on proteins binding nucleosomal DNA is too limited for the rational design of new drugs. The current proposal aims to combine expertise of the researcher (on protein design) and the host group (on DNA and protein-DNA interactions) to computationally design and experimentally test proteins binding nucleosomal DNA with specificity. The researcher will first develop a computational design protocol and subsequently test it against nucleosomes of known structure. After experimental validation, he will design proteins blocking the nucleosomal DNA sites targeted by two proteins (FoxA1 and GATA) known to promote breast and prostate cancer. The proposed project uses computational approaches for designing protein structures and protein-DNA interactions, and experimental approaches to characterize protein-DNA binding and structure of the designed complexes. This multidisciplinary project is devised to expand the design capabilities of the researcher towards protein-DNA interactions, which hold great potential for medical and biotechnological applications, in a research context of high biomedical impact. This project devises a training plan on computational, experimental and transferable skills necessary for an independent research position, and provides an opportunity to bring protein design approaches into the European research. The novelty of this protein-DNA design approach will be of wide interest for the scientific and non-scientific communities, and will be disseminated accordingly.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MSCA-IF-EF-RI - RI – Reintegration panel

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2016

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Coordinator

FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA)
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.

€ 170 121,60
Address
CARRER BALDIRI REIXAC 10-12 PARC SCIENTIFIC DE BARCELONA
08028 BARCELONA
Spain

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Region
Este Cataluña Barcelona
Activity type
Research Organisations
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 170 121,60
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