Objective
The proteins of the Bcl-2 family function as key regulators of apoptosis by controlling the permeabilization of the mitochondrial outer membrane. They form an intricate, fine-tuned interaction network which is altered in cancer cells to avoid cell death. Currently, we do not understand how signaling within this network, which combines events in cytosol and membranes, is orchestrated to decide the cell fate. The main goal of this proposal is to unravel how apoptosis signaling is integrated by the Bcl-2 network by determining the quantitative Bcl-2 interactome and building with it a mathematical model that identifies which interactions determine the overall outcome. To this aim, we have established a reconstituted system for the quantification of the interactions between Bcl-2 proteins not only in solution but also in membranes at the single molecule level by fluorescence correlation spectroscopy (FCS).
(1) This project aims to quantify the relative affinities between an reconstituted Bcl-2 network by FCS.
(2) This will be combined with quantitative studies in living cells, which include the signaling pathway in its entirety. To this aim, we will develop new FCS methods for mitochondria.
(3) The structural and dynamic aspects of the Bcl-2 network will be studied by super resolution and live cell microscopy.
(4) The acquired knowledge will be used to build a mathematical model that uncovers how the multiple interactions within the Bcl-2 network are integrated and identifies critical steps in apoptosis regulation.
These studies are expected to broaden the general knowledge about the design principles of cellular signaling as well as how cancer cells alter the Bcl-2 network to escape cell death. This systems analysis will allow us to predict which perturbations in the Bcl-2 network of cancer cells can switch signaling towards cell death. Ultimately it could be translated into clinical applications for anticancer therapy.
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
- natural sciences physical sciences optics microscopy
- medical and health sciences clinical medicine oncology
- natural sciences physical sciences optics spectroscopy
- natural sciences mathematics applied mathematics mathematical model
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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-2012-StG_20111109
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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.
Host institution
72074 Tuebingen
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.