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MyeRIBO

Financiado

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... ver más

30/09/2025

USC

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

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

Total investigadores 236

Ver 3 Participantes

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2020-01-28

ERC-2019-COG: ERC Consolidator Grant

I+D

Cerrada hace 5 años

0% 100% 100%

3 Participantes

USC

1.86M€ | Lider

ALCALA INDUSTRIAL SA

957.84K€ | Participante

ASOCIACION CENTRO DE INVESTI...

14.48K€ | Participante

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Duración del proyecto: 68 meses Fecha Inicio: 2020-01-28
Fecha Fin: 2025-09-30

Líder del proyecto

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

Total investigadores 236

Presupuesto del proyecto 2M€

Descripción del proyecto 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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