Objective
Cells respond to extracellular stress by inducing specific intracellular programs through the activation of stress kinase signalling pathways. Stress responses are associated with the phosphorylation of particular substrates implicated in restoring homeostasis and cell integrity. Oncogene activation has also been shown to generate replicative DNA damage, activate the DNA Damage Response (DDR) and thereby limit the expansion of precancerous cells. At the molecular level, the DDR is a functional network of different proteins that cooperate in arresting the cell cycle and repairing DNA damage, or inducing cell death if the damage exceeds repair capacities. Recently, micro (mi)RNAs were shown to regulate the expression of several DDR proteins. However, it is not known whether the activity of miRNAs is affected by the stress response. miRNAs are a class of small regulatory RNAs that repress translation and induce degradation of their target mRNAs. Argonaute (Ago) proteins are essential for miRNA activity by forming the central component of the RNA-induced silencing complex. Preliminary data from the Stoecklin lab show that Ago-2 and miRNA-dependent mRNA decay are inhibited in response to oxidative stress, one of the major causes for DNA damage. We propose to investigate the mechanisms of Ago-2 regulation in response to oxidative stress and other DNA damage agents, with the aim to identify possible phosphorylation sites in Ago-2, elucidate the signalling pathways involved, and examine the physiological consequences of Ago-2 inhibition on the cell cycle, the apoptotic response and cell transformation. We will further address specific interactions that Ago-2 undergoes under conditions of oxidative stress with the phosphatase PP6c, the proteasome and the SMN complex. Taken together, the proposed work will elucidate mechanisms that control Ago-2 function and miRNA activity, which will have significant impact on our understanding of RNA interference.
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
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics RNA
- medical and health sciences basic medicine physiology homeostasis
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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-2011-IEF
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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
69120 Heidelberg
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.