Objective
DNA damage induces cell cycle arrest, required for the action of repair mechanisms. The genes of these pathways affect cells' sensitivity to DNA damage, and their loss may lead to deregulated cellular growth, genomic instability and cancer. Until now, our knowledge in this field was gained mainly from work in cells of DNA damage-sensitive individuals and from lower eukaryotes. Improving our understanding of these processes in mammals was hampered due to lack of suitable genetic tools. Recently, we developed a vector-based system that generates persistent loss-of-function phenotypes in mammalian cells by production of short interfering RNA (siRNA). A siRNA-expressing library to suppress up to 8000 human genes was constructed in our institute and is consent to perform genome wide loss-of-function screens.
The proposal includes:
1) Screen for novel genes participating in DNA damage response pathways;
2) Elucidating the roles of these genes in DNA damage response pathways;
3) Evaluating the contribution of these genes to malignancy.
I will screen primary human cells for genes involved in sensitising cells to genotoxic stress, and genes that synergize with radio- and chemotherapy agents in tumour cell killing. I will investigate the mechanism of action of the identified genes in DNA damage response pathways, and will assess their tumour suppressive/oncogenic properties. The identification of novel genes modulating cellular toxicity induced by DNA damage will improve our understanding of the action genotoxic agents, and will provide new opportunities to screen for drugs that sensitise tumours to conventional therapy.
This project will render the siRNA library system extremely beneficial for mammalian models and research fields, encouraging the transfer of research competencies across different labs. My training in this project will complement my contemporary expertise and will diversify them considerably, contributing to my development as an independent researcher.
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: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences genetics genomes
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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.
FP6-2002-MOBILITY-5
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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
AMSTERDAM
Netherlands
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.