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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. €

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.

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

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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lastchecktime (2021-05-15 12:13:17) correctly updated