Project description
The origins of neurodevelopmental disorders
Neurodevelopmental disorders (NDDs) such as Fragile X syndrome are increasing in prevalence, yet their molecular origins remain unclear. Supported by the Marie Skłodowska-Curie Actions programme, the Neuro-Phase project will investigate how disruptions in liquid-liquid phase separation (LLPS), a process critical for regulating protein production, may contribute to altered brain development. Using human brain organoids and embryonic brain tissue models, Neuro-Phase will explore how early disturbances in LLPS affect neural circuit formation. By clarifying these mechanisms, the project aims to improve understanding of the early biological events leading to NDDs and to inform future therapeutic strategies.
Objective
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.
Fields of science (EuroSciVoc)
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2024-PF-01
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700 13 IRAKLEIO
Greece
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