Objective
All aspects of brain function rely on the interplay between networks of functionally related neuronal cells. These cells are connected by “synapses”, which are specialized cellular compartments dedicated to rapid electrical and chemical signalling. Excitatory neurotransmission in the vertebrate central nervous system (CNS) is largely mediated by the ionotropic glutamate receptors (iGluRs). These postsynaptic receptors conduct cations into the cell in response to binding of the neurotransmitter glutamate released from presynaptic vesicles. Accumulation and positioning of iGluRs at neuronal synapses are crucial for enabling correct neurotransmission. While it is known that extracellular scaffolding proteins (ESPs) interact with iGluRs to stabilize these receptors at synapses, the transient, low-affinity nature of these protein interactions has so far precluded complex structure determination and therefore a precise mechanistic understanding of their function. The aim of this proposal is to implement state-of-the-art techniques of protein engineering to stabilise iGluR:ESP interactions for structure determination by affinity maturation of their interaction interfaces. I will focus on two well-established complexes: Cerebellin-Glutamate receptor Delta (Cbln-GluD) and Neuronal Pentraxin-AMPA receptor (NP-AMPAR). Structural insights into the full-length synapse-spanning Cbln-GluD and NP-AMPAR interactions will elucidate how clustering and trans-synaptic anchoring of iGluRs contribute to synaptic transmission, as well as pave the way for the design of engineered synaptic organizer proteins capable of remodelling synapses. During this project I will gain experience in protein engineering which will allow me to establish a career as an independent scientist with a focus on tackling complex structural biology problems with translational applications.
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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.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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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.
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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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.
(opens in new window) HORIZON-MSCA-2021-PF-01
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
75794 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.