Objective
Rho-family GTPases control many aspects of cell behavior through the regulation of multiple signaling pathways. Failure to properly regulate Rho GTPases can have deleterious consequences in human development and disease. A key group of spatial and temporal regulators of Rho-family GTPases are the Rho GEF proteins. Rho GEFs serve to couple diverse regulatory stimuli to Rho GTPase activation. There are a large number of Rho GEFs encoded by the human genome and a systematic study addressing cellular function is needed. With this proposal, I aim to complete an unbiased large-scale functional analysis of all the Rho GEF proteins using a lentiviral-RNAi based strategy to identify Rho-family GEF proteins involved in epithelial cell morphogenesis. To achieve this project I will use the three-dimensional Madin-Darby canine kidney epithelial cell (3D-MDCK) system, which is an excellent model to investigate epithelial morphogenesis in vitro. I will verify RNAi mediated knockdown of expression for candidate GEFs and demonstrate that the phenotypes caused by RNAi are not primarily due to off-target effects. Then, I will characterize the phenotypes of Rho GEF RNAi knockdowns in detail and determine the subcellular localization of the GEF proteins. Finally, I aim to determine the Rho GTPase specificity for Rho GEF candidates. The analysis of Rho GEF function in the MDCK 3D cell culture system might have particular relevance to cancer since their aberrant regulation can lead to malignant transformation and a majority of human tumors are thought to be epithelial in origin. In this proposal, I will carry out a more systematic, genome wide knockdown of all known human Rho GEFs with the goal of identifying and characterizing important regulators of MDCK epithelial cell morphogenesis. I hope that the insights I gain from the analysis of Rho GEF function in MDCK epithelial cells will aid our understanding of development and disease in both the kidney and other epithelial tissues.
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 biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
- natural sciences mathematics pure mathematics mathematical analysis functional analysis
- natural sciences biological sciences genetics genomes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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-2007-4-3-IRG
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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
28006 Madrid
Spain
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.