Objective
Somatically acquired loss-of-heterozygosity (LOH) is extremely common in cancer; deletions of recessive cancer genes, miRNAs, and regulatory elements, can confer selective growth advantage, whereas deletions over fragile sites are thought to reflect an increased local rate of DNA breakage. However, most LOHs in cancer genomes remain unexplained. Here we plan to combine a TALEN technology and the experimental models of cell transformation derived from primary human cells to delete specific chromosomal regions that are frequently lost in cancer samples. The development of novel strategies to introduce large chromosomal rearrangements into the genome of primary human cells will offer new perspectives for studying gene function, for elucidating chromosomal organisation, and for increasing our understanding of the molecular mechanisms and pathways underlying cancer development.Using this technology to genetically engineer cells that model cancer-associated genetic alterations, we will identify LOH regions critical for the development and progression of human cancers, and will investigate the cooperative effect of loss of genes, non-coding RNAs, and regulatory elements located within the deleted regions on cancer-associated phenotypes. We will assess how disruption of the three-dimensional chromosomal network in cells with specific chromosomal deletions contributes to cell transformation. Isogenic cell lines harbouring targeted chromosomal alterations will also serve us as a platform to identify compounds with specificity for particular genetic abnormalities. As a next step, we plan to unravel the mechanisms by which particular homozygous deletions contribute to cancer-associated phenotypes. If successful, the results of these studies will represent an important step towards understanding oncogenesis, and could yield new diagnostic and prognostic markers as well as identify potential therapeutic targets.
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.
- natural sciences biological sciences genetics DNA
- 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.
ERC-2012-StG_20111109
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.
Host institution
9052 ZWIJNAARDE - GENT
Belgium
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.