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SynLink SIGNED

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

Total Cost €

0

EC-Contrib. €

0

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.

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

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

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 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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