Objective
The aim of this project is to uncover a novel regulatory mechanism that explains how cells change their membrane lipid composition and trafficking as a function of population context, and how that is used to adapt the cell’s physiology to its microenvironment. To do so, I will use single cell microscopy over large populations, lipidomic, phosphoproteomic and microarray analysis of mice cells deleted from Focal Adhesion Kinase (FAK).
When cells grow at low local cell density or at the edges of cell islets, FAK becomes activated. This event activates signalling and gene regulation. Interestingly, silencing of FAK strongly impairs sphingolipid GM1 amount at the plasma membrane and fate through clathrin-independent endocytosis, leading to drastic diminution of Simian Virus 40 (SV40) infection. Microarray analysis of FAK-KO cells and Wild Type, in dense and sparse contexts, shows that lysosomal, Golgi apparatus and trafficking genes are controlled by activated Focal Adhesion Kinase. ABCA1, a membrane scrambler and cholesterol efflux mediator, is the second overall strongest hit and the only membrane protein amongst the top hits. Strikingly the loss-of-FAK phenotype in cell spreading and growth can be reversed by inhibiting ABCA1, suggesting that FAK act on membranes by controlling ABCA1 production.
I would like to characterise the actors and dynamics of the FAK-ABCA1 system to understand how it couples membrane composition and clathrin-independent trafficking to local environments. I will apply i)phosphoproteomic approach and chromatin Immunoprecipitation for finding key signalling axis from FAK activation to gene regulation, ii)lipidomic for characterizing FAK effect on membrane composition, and iii)leading edge single cell microscopy over large populations both in live or fixed conditions in order to characterise the FAK-ABCA1 system effect on membrane ordering and sphingolipid endocytosis to the Golgi apparatus or lysosome, as a function of cell density
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 microbiology virology
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy
- natural sciences biological sciences biochemistry biomolecules lipids
- medical and health sciences basic medicine physiology
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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
8006 ZURICH
Switzerland
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.