CellCellEM
Financiado
Communications at the Synapse a Near Atomic Resolution View into Cell Cell Com...
Communications at the Synapse a Near Atomic Resolution View into Cell Cell Communication in the CNS
Synapses are intercellular junctions specialized for coordinated cell-cell communication throughout the nervous system. They are organized by cell-adhesion molecules (CAMs) that bi-directionally orchestrate neuronal communication....
Synapses are intercellular junctions specialized for coordinated cell-cell communication throughout the nervous system. They are organized by cell-adhesion molecules (CAMs) that bi-directionally orchestrate neuronal communication. Latrophilins (LPHNs) are a unique sub-family of CAMs that play critical roles in structuring the synaptic architecture through multifaceted interactions with a large variety of synaptic partners. Mutations in LPHN have been associated with neurodevelopmental and neuropsychiatric disorders. Despite their gravity, the mechanism governing LPHN synaptic activities remain elusive.
To further our understanding of LPHN-mediated cell-cell communication, we suggest to characterize these receptors’ interactions with their intracellular and extracellular partners. For this purpose, we propose to adopt a hybrid approach driven primarily by cryo-EM, a state-of-the-art technique capable of dissecting the molecular mechanisms of super-molecular assemblies at extremely high spatial resolutions, which is our group’s main field of expertise. The cryo-EM studies will be complemented by cryo electron tomography (cryo-ET), fluorescence microscopy and biochemical approaches. Our specific aims are:
Aim 1: Dissect the molecular mechanisms of LPHN activation by combining cryo-EM with biochemical methodologies.
Aim 2: Characterize the LPHN interactome through cryo-EM and fluorescence microscopy.
Aim 3: Resolve the architecture of the LPHN interactome at a close-to-native environment through cryo-ET.
Our experimental strategy will generate a quantitative, near-atomic resolution view of LPHNs and the mechanism by which they interact with their synaptic partners and instigate trans-synaptic signal transduction. These data will be vital for understanding LPHN-mediated cell-cell communication as well as the mechanisms governing trans-synaptic interactions and could potentially highlight novel approaches to treat neurodevelopmental and neuropsychiatric disorders.
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Duración del proyecto: 60 meses
Fecha Inicio: 2020-10-05
Fecha Fin: 2025-10-31
Fecha Fin: 2025-10-31
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2020-10-05
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2020-STG:
ERC STARTING GRANTS
Cerrada
hace 5 años
Presupuesto
El presupuesto total del proyecto asciende a
1M€
Líder del proyecto
WEIZMANN INSTITUTE OF SCIENCE
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
958.98K€ |
Participante