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SynLink SIGNED

Molecular Structure and Engineering of Synaptic Organizer Proteins in Health and Disease

Total Cost €

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EC-Contrib. €

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Partnership

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 SynLink project word cloud

Explore the words cloud of the SynLink project. It provides you a very rough idea of what is the project "SynLink" about.

neurodegenerative    neuroscience    exploited    differentiation    specialized    leverage    function    animal    units    molecular    basis    communication    mechanism    dysfunction    models    soluble    specified    imaging    pave    deterioration    cognitive    synapses    electron    restoring    cryo    interactions    largely    disease    organizer    membrane    basic    recovery    crystallography    structure    elucidate    recruit    ray    cellular    mechanistic    alzheimer    hallmarks    simultaneously    electrophysiology    mouse    display    signalling    receptors    structural    functions    modifying    biology    combinatorial    culture    dementia    junctions    question    circuitry    microscopy    nanocolumn    functionalize    degeneration    machinery    structures    synaptic    variants    generating    therapies    engineering    interaction    form    anchored    dependent    variety    adhesive    principles    organizers    persistent    reveal    connectivity    underlie    insights    surface    neurotransmitter    engineered    mediate    cognition    yeast    neurons    synapse    screening    proteins    neurotransmission    ad    trans    lacking    network    organize    repair    cells    remodel    fundamental    defects    biophysical    combine    neuronal    techniques    reverse    protein   

Project "SynLink" data sheet

The following table provides information about the project.

Coordinator
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS 

Organization address
address: RUE MICHEL ANGE 3
city: PARIS
postcode: 75794
website: www.cnrs.fr

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country France [FR]
 Total cost 1˙499˙903 €
 EC max contribution 1˙499˙903 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2019-STG
 Funding Scheme ERC-STG
 Starting year 2020
 Duration (year-month-day) from 2020-03-01   to  2025-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS FR (PARIS) coordinator 1˙499˙903.00

Map

 Project objective

Synapses are the specialized cellular junctions that form the basic units of communication between neuronal cells. Given the variety of network-dependent functions that synapses need to support, a fundamental question is how their properties are specified at the molecular level. Membrane-anchored and soluble “synaptic organizer proteins” form adhesive interactions that mediate synapse formation and differentiation. However, a structural and mechanistic understanding of how they recruit and organize the molecular machinery for neurotransmission is largely lacking. Simultaneously, dysfunction of synapses and loss of neurons are hallmarks of neurodegenerative disease that underlie a persistent deterioration of cognitive functions. The properties of synaptic organizer proteins to form and functionalize synapses could be exploited as a mechanism for synaptic repair to reverse neuronal degeneration.

The aims of this proposal are (i) to reveal the structural basis for trans-synaptic molecular nanocolumn formation by determining the complex structures of synaptic organizer proteins and neurotransmitter receptors, and (ii) to leverage insights into the structure and function of soluble synaptic organizers for generating engineered variants that can remodel synapses with the potential for restoring neuronal circuitry and cognition in animal models of Alzheimer’s disease (AD), the most common form of dementia associated with early defects in synaptic function.

To achieve these aims, I will combine techniques of structural biology (X-ray crystallography, cryo-electron microscopy and biophysical interaction analysis), protein engineering (combinatorial screening using yeast surface display), and cellular neuroscience (neuronal culture, electrophysiology, advanced imaging and mouse models). Our results will elucidate fundamental principles of synaptic signalling and pave the way for disease-modifying therapies that focus on recovery of synaptic connectivity and function.

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The information about "SYNLINK" are provided by the European Opendata Portal: CORDIS opendata.

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