Objective
Complex dynamic protein-protein interactions are the base of protein-based networks in cells. Among them, the synaptic connection between two neurons is one of the most challenging. The postsynaptic density (PSD) at excitatory synapses in the brain is a prototypical example of protein-based network whose nanoscale structure and composition determines cellular function. Moreover, dynamic regulation of PSD composition and receptor movement into or out of the PSD is the base of current molecular theories of learning and memory. However, the nature of this regulation remains poorly understood partly due to the lack of tools that would allow disruption and control of specific interactions.
Several key components of the PSD such as PSD-95 contain multiple PDZ domains and the interactions mediated by these small domains are involved in critical events such as synaptic targeting and anchoring of glutamate receptors (AMPARs, NMDARs). The aim of this project is to design and exploit original tools to better understand the role of PDZ domain-mediated interactions in the context of synaptic plasticity by employing a chemical biology approach associating synthesis, biophysical measurements and live cell studies. In particular two different aspects will be addressed: 1) development of efficient and specific competing biomimetic ligands that integrate the multivalent nature of these interactions and 2) spatio-temporal control of the disruption of these PDZ domain-mediated interactions by incorporating to the previous ligands photolabile caging groups. The specific targets comprise on the one hand the main synaptic PDZ domain-containing scaffolding proteins (PSD-95, SAP97, PSD-93 and SAP102) and on the other AMPA and NMDA receptor complexes. Finally, these tools will complement common biological approaches by allowing us to study localized and dynamic macromolecular events between endogenous proteins.
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.
FP7-PEOPLE-2010-IEF
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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
33076 BORDEAUX CEDEX
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.