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SynLink SIGNED

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

Total Cost €

0

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.

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

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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