Objective
"Genome integrity is constantly challenged by endogenous and environmental factors that can induce different types of DNA lesions. Failure to repair DNA lesions can lead to genomic instability and contribute to human diseases such as cancer and premature ageing. To counteract these potentially devastating effects caused by DNA damage, eukaryotic cells have evolved complex DNA repair pathways. Protein ubiquitylation has emerged as an important regulatory mechanism of the cellular response to DNA damage: Ubiquitin-modifying enzymes are recruited to sites of DNA damage and are essential for the repair of DNA lesions. However, for most of these enzymes the protein substrates that are modified in response to DNA damage and the molecular functions in DNA damage signalling remain obscure.
Recent advances in mass spectrometry as well as novel methods for the enrichment of ubiquitylated peptides permit to systematically study protein ubiquitylation after cellular perturbations. In the proposed research project we plan to perform a quantitative analysis of protein ubiquitylation in ubiquitin ligase knockdown cells to identify the physiological substrates of ubiquitin ligases that function in DNA repair and chromatin organization. To this end, the cellular expression of selected ubiquitin ligases, including RAD18, BRCA1/BARD1, RNF20/40 and RING1A/RING1B/BMI1, will be downregulated by transient transfection of siRNA. Wildtype and knockdown cells will be treated with DNA damage-inducing agents and the ubiquitylation patterns in these cells will be comparatively analyzed using quantitative mass spectrometry. Biochemical and cell biological methods will be employed to characterize the physiological relevance of the site-specific protein ubiquitylation for the target proteins. These investigations are expected to uncover ubiquitin ligase – substrate relations and to deepen the understanding of the regulatory roles of ubiquitin ligases in processes that maintain chromatin integrity."
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 chemical sciences analytical chemistry mass spectrometry
- natural sciences biological sciences genetics genomes
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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-2013-CIG
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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.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
55128 Mainz
Germany
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.