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MyeRIBO

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Deconstructing the Translational Control of Myelination by Specialized Ribosomes

The myelin sheath is essential for neuronal function and health: myelinating glial cells speed up propagation of axonal potentials, fuel the energetic demands and regulate the ionic environment of neurons. Lesions to the myelin sh... see more

30/09/2025

USC

2M€

Project Budget: 2M€

Project leader

UNIVERSIDAD DE SANTIAGO DE COMPOSTELA No se ha especificado una descripción o un objeto social para esta compañía.

total researchers 240

PARTICIPATION DEPralty Sin fecha límite de participación.

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Financing granted El organismo H2020 notifico la concesión del proyecto The day 2020-01-28

ERC-2019-COG: ERC Consolidator Grant Scope:Objectives

I+D

Cerrada does 6 years

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characteristics of the participant

Este proyecto no cuenta con búsquedas de partenariado abiertas en este momento.

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3 Participantes

USC

1.86M€ | Leader

ALCALA INDUSTRIAL SA

957.84K€ | participant

ASOCIACION CENTRO DE INVESTI...

14.48K€ | participant

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Project duration: 68 months Date Start: 2020-01-28
End date: 2025-09-30

Project leader

UNIVERSIDAD DE SANTIAGO DE COMPOSTELA No se ha especificado una descripción o un objeto social para esta compañía.

total researchers 240

Project Budget 2M€

participation deadline Sin fecha límite de participación.

Project description The myelin sheath is essential for neuronal function and health: myelinating glial cells speed up propagation of axonal potentials, fuel the energetic demands and regulate the ionic environment of neurons. Lesions to the myelin sheath thus result in devastating neurological disorders that include multiple sclerosis, diabetic neuropathy and Charcot-Marie-Tooth disease. Myelination involves a striking expansion of the glial cell membrane that relies on an exceptional increase in protein and lipid synthesis rates. Decades of dedicated research has uncovered a complex transcriptional program that drives this process, whereas translational control mechanisms, on the other hand, have received little attention. There is emerging evidence, enabled by modern techniques, that ribosomes, typically viewed as invariant, passive molecular machines, may instead be heterogeneous in composition, with particular ribosomal components having a ‘specialized’ regulatory capacity for preferential translation of specific mRNAs. In MyeRIBO, I propose that translation control by specialized ribosomes is a novel layer of regulation that shapes the proteome of the myelinating glial cell. I will exploit advances in cryo-EM and quantitative proteomics analyses to discover the nature and diversity of ribosomes in myelinating cells, employ genome-wide ribosome profiling to obtain mechanistic insights into selective mRNA translation by heterogeneous ribosomes, and generate genetic mouse models to determine the functional consequences of this specialization for myelination in vivo. Notably, I will study the implication of this mechanism in pathogenesis of injury-induced demyelination and diabetic neuropathy, and evaluate the targeting of specialized ribosomal components as a preclinical strategy. MyeRIBO will push further the boundaries of our current understanding of the molecular control of myelination, which could have a profound impact for understanding neural development and myelin disorders.

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