Objective
The Rho-GTPase Cdc42 is a key regulator of the actin and microtubule network, thereby regulating cellular processes like cell polarization and motility or membrane traffic. Two isoforms of Cdc42 exist; one ubiquitously expressed, the other being brain-specific. Most studies have focused on the former and specific functions of the brain-restricted variant remain obscure. Recent observations from Etienne-Manneville’s lab uncover an isoform-specific alteration of Cdc42 expression in glioblastoma, a most invasive type of brain tumour, leading us to investigate the individual functions of each variant. In this project, we will compare the intracellular localization patterns of the two isoforms and investigate the underlying targeting mechanisms. The individual subset of binding partners will be analyzed, as well as how alterations of Cdc42 variants expression may affect membrane protrusion, polarization and motility in normal astrocytes. Results will then be compared to that of reconstituted or RNAi-treated glioblastoma cells, in order to define the consequences of abnormal expression of Cdc42 isoforms in the invasiveness of brain tumour cells. Furthermore, variants of the polarity proteins aPKC and Par6, which were also found to be misregulated in glioblastoma, will be analysed for their individual relevance in the context of migration and polarity. Understanding the regulatory background leading to the high invasiveness of glioblastoma is most important, as single tumour cells commonly infiltrate brain tissue several centimetres away from the main tumour, making a complete surgical clearance impossible. Characterizing “risk factors” in glioblastoma progression, as potentially given by misregulated expression of proteins influencing cell migration and polarity, may furthermore allow predicting more precisely the development of brain tumours and may provide the basis for novel therapies aimed at blocking tumour cell infiltration as a complement to surgical interventions.
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 biochemistry biomolecules proteins
- natural sciences biological sciences cell biology cell polarity
- medical and health sciences clinical medicine surgery surgical procedures
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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
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.
Coordinator
75724 Paris
France
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.