Objective
Cellular growth and migration depend on intracellular communication webs mediated by polypeptide growth factors. One example comprises EGF-like growth factors and their ErbB receptor tyrosine kinases. EGFR and HER2 are frequently involved in cancer progression, and they serve as targets for cancer therapeutics. The existence of a kinase-dead receptor, as well as the emergence of resistance in patients treated with EGFR and HER2 blockers, instigated a paradigm shift from a linear EGF-to-ErbB cascade to a robust network characterized by multiple feedback loops.
We assume that deregulation of feedback loops plays essential roles in human cancer. Because of the abundance of feedback regulation, we predict subtle, multi-component impact on disease.
Aiming at the natural richness of feedback regulation in breast cancer, we will develop in vitro models of normal mammary cells, and introduce genetic, disease-mimicry manipulations. Two time domains of feedback regulation will be addressed: (i) the early domain of post-translational modifications, which we will explore using proteomic approaches. And (ii) the late domain comprising alterations in transcription, micro-RNAs and alternative splicing, processes we will investigate using deep sequencing and array technologies. Once verified and characterized in normal cells, we will survey the operational status of the unravelled feedback loops in genetically manipulated cell systems and in tumour specimens, using immunological and bio-informatical approaches.
Detailed knowledge of feedback regulation of multi-layered signalling networks, such as ErbB, is expected to shed light on the currently elusive basis of signal integration and elimination of noise, as well as identify markers of prognosis.
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.
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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-2010-AdG_20100317
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
7610001 Rehovot
Israel
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.