Objective
Each cell in the human body receives thousands of DNA lesions per day. To counteract threats posed by DNA damage, cells have evolved an integrated signaling network called the DNA-damage response (DDR). This mechanism allows cells to detect DNA lesions, signal their presence and promote their repair. Mutation of DDR genes, which serves as a biological barrier against tumor progression, leads to cancer development2. A large-scale proteomic analysis of proteins phosphorylated in response to DNA damage by checkpoint kinases ATM and ATR identified extensive protein networks responsive to DNA damage. Interestingly, among the proteins identified to be phosphorylated upon DNA damage were several nuclear pore complex factors including nucleoporin Translocated Promoter Region (TPR)5. TPR was previously linked to cancer since its N-terminal domain has been found fused with the protein kinase domains of various proto-oncogenes such as RAF and MET resulting in human solid tumors. TPR expression level was found deregulated in many types of human tumors such as breast and liver cancer8. Amplification of TPR was also significantly associated with a shorter survival of patients with pediatric intracranial ependymomas9. All these findings support a critical role for TPR in the mechanism of oncogenesis. By employing state-of-the-art proteomics (SILAC), genetics (in vitro mutagenesis), genomics (DNA binding profiling) and imaging (electron microscopy) technologies we will investigate how TPR prevents tumor genesis via its role in the DDR network coordinating DNA repair, DNA replication and chromatin condensation with the nuclear envelope upon DNA damage. Providing mechanistic insight into the role of TPR in DDR and the maintenance of genome stability will not only contribute to our understanding of molecular principles of response to damaged DNA, but will allow us to optimize existing cancer treatments and design new molecular targeted therapies in the future.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences clinical medicine oncology liver cancer
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- natural sciences biological sciences genetics DNA
- natural sciences physical sciences optics microscopy electron microscopy
- medical and health sciences basic medicine neurology
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
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.
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-ST - Standard EF
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2015
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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.
20139 Milano
Italy
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.