Objective
Cancer imposes a tremendous socioeconomic burden in modern societies, causing ~1.7 million deaths in the EU annually. 15-20% of these cases occur due to mutations in the oncosuppressor gene p53, which destabilize the protein and inactivate its ability to mediate apoptosis under physiological conditions. Today, no drugs exist which can restore the function of mutant p53 and treat cancer. The present proposal deals with the discovery of potential cancer therapeutics of this type. The topic of the proposed research is the directed evolution of small molecules which can bind to and restore the folding and function of destabilized oncogenic variants of p53 (p53*). These compounds will be selected from libraries of small molecules which will be biosynthesized in microbial cells. Biosynthesis will be carried out using an approach that allows for facile preparation of a very large number of test compounds, which will exhibit high levels of chemical and structural diversity. These small-molecule libraries will then be screened and the compounds which can bind to and improve the folding of p53* will be identified using a high-throughput genetic screen. The effect of the identified compounds on the stability of p53* will be subsequently evaluated in vitro by using biochemical and biophysical methods of protein analysis, and their ability to revitalize apoptosis will be tested in selected human cancer cell lines. The compounds which will be found capable of restoring the stability and apoptosis-mediating function of p53* will become drug candidates against a broad panel of cancers.
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 basic medicine pharmacology and pharmacy drug discovery
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology
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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.
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.
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.
FP7-PEOPLE-2010-RG
See other projects for this call
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.
Coordinator
11 635 ATHINA
Greece
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.