Objective
Poly(ADP)ribosylation (pARylation) is an important post-translational modification of proteins that affects diverse biological processes such as DNA damage repair, apoptosis and transcription. The conjugation of Poly(ADP)-ribose (pADPr) to target proteins is mediated by members of the Poly(ADP)-ribose polymerase (ARTD/PARP) protein family. ADPr can be attached either as a single moiety or as chains forming poly-ADPr polymers (pADPr). The best-studied member of the ARTD/PARP family is ARTD1/PARP1, a DNA nick sensor enzyme that is activated following DNA damage. ARTD1/PARP1 is able to pARylate itself and a number of other protein targets, such as histones and DNA repair proteins, modulating their activity. Another member of this super-family is the telomeric ARTD/PARP, Tankyrase 1 (ARTD5/TNKS1), which plays an important role in maintaining telomere integrity, by pARylating its telomere partner, TRF1. Since the discovery that defects in homologous recombination sensitise cancer cells to PARP inhibitors there has been a renewed interest in ARTD/PARPs as attractive therapeutic targets. Furthermore, similarly to kinases and phosphorylation it seems likely that ARTD/PARPs and pARylation will have significant roles in the controls of a diverse range of cellular mechanisms. Using a combined approach of RNA interference (RNAi), drug treatment and mass spectrometry-based proteomic analysis, I propose to identify and characterise novel mono- and poly-(ADP)ribosylation targets, specific to particular ARTD/PARPs. This will help to resolve how (ADP)r conjugation regulates biological processes and contributes to the survival and maintenance of cancer cells. Moreover, using pathway specific reporter cell lines I will address the specific contribution of mAR/pARylated proteins for the regulation of several cancer-related signalling pathways. Ultimately, these studies will reveal novel and promising pARylation-based therapeutic targets for cancer treatment.
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 chemical sciences polymer sciences
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics RNA
- 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-2010-RG
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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
SW7 3RP London
United Kingdom
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.