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Liquid-Liquid Phase Separation and Translational Control in the developing cortex and its implications for Neurodevelopmental Disorders.

Descrizione del progetto

Le origini dei disturbi del neurosviluppo

I disturbi del neurosviluppo (DNS), come la sindrome dell’X fragile, sono sempre più diffusi, ma le loro origini molecolari sono tuttora poco chiare. Con il sostegno del programma di azioni Marie Skłodowska-Curie, il progetto Neuro-Phase studierà come le interruzioni nella separazione di fase liquido-liquido (SFLL), un processo cruciale per la regolazione della produzione di proteine, possano contribuire ad alterare lo sviluppo del cervello. Utilizzando organoidi cerebrali umani e modelli di tessuto cerebrale embrionale, Neuro-Phase indagherà come i disturbi precoci della SFLL influenzino la formazione dei circuiti neurali. Chiarendo questi meccanismi, il progetto si propone di comprendere meglio gli eventi biologici precoci che portano ai DNS e di orientare le strategie terapeutiche future.

Obiettivo

Neurodevelopmental disorders (NDDs), including Fragile X Syndrome (FXS), are a heterogeneous group of conditions leading to difficulties with speech, learning and other neurological functions greatly affecting patients and healthcare, societal, and educational systems. The rising prevalence of NDDs highlights the urgent need to understand their origins, often rooted in early cortical development. In humans, the cerebral cortex, responsible for cognitive functions like language and learning, is susceptible to disruptions during early brain development, a process tightly regulated by neuronal growth and protein synthesis. The coordination of biochemical events in eukaryotic cells, including protein synthesis, is facilitated by compartmentalizing key molecules either into organelles or as membraneless condensates via liquid-liquid phase separation (LLPS). LLPS is crucial for neurotransmission, memory, and synaptic plasticity. The fragile X messenger ribonucleoprotein 1 (FMRP) has been shown to undergo LLPS with the translation factor 4E-BP2 (eukaryotic initiation factor 4E binding protein 2), a key regulator in the mechanistic target of rapamycin (mTOR) signaling pathway implicated in both autism and FXS and the development of cortical outer radial glia. The Neuro-Phase project will investigate the role of LLPS and the molecular and cellular mechanisms involved in NDDs and more specifically the role of 4E-BP2-FMRP LLPS interaction in translational control and early human brain development which has yet to be explored. To test this hypothesis, the Neuro-Phase project will use innovative biological models, including human induced pluripotent stem cell-derived brain organoids and organotypic cultures of post-mortem human embryonic cortical explants. This project will provide critical insights into the pathogenesis of NDDs by identifying potential therapeutic targets, that leverage cellular intrinsic mechanisms like LLPS, to mitigate or prevent these conditions.

Campo scientifico (EuroSciVoc)

Parole chiave

Programma(i)

Argomento(i)

Meccanismo di finanziamento

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Invito a presentare proposte

(si apre in una nuova finestra) HORIZON-MSCA-2024-PF-01

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Coordinatore

IDRYMA TECHNOLOGIAS KAI EREVNAS
Contributo netto dell'UE
€ 181 423,68
Indirizzo
N PLASTIRA STR 100
700 13 IRAKLEIO
Grecia
Regione
Νησιά Αιγαίου Κρήτη Ηράκλειο
Tipo di attività
Research Organisations
Collegamenti
Costo totale
Nessun dato

Partner (1)