Innovating Works

NEUROGLIOSOLVE

Financiado
RNA biology and neuroglial function: resolving the cellular and subcellular tran...
RNA biology and neuroglial function: resolving the cellular and subcellular transcriptome in myotonic dystrophy brains, towards new brain gene therapy RNA biology is critical for the molecular orchestration of the interplay between specialized brain cell types, and disrupted RNA processing, can cause human disease. A prime example is Myotonic Dystrophy type 1(DM1), a multisystem... RNA biology is critical for the molecular orchestration of the interplay between specialized brain cell types, and disrupted RNA processing, can cause human disease. A prime example is Myotonic Dystrophy type 1(DM1), a multisystemic disorder caused by the expansion of a non-coding trinucleotide DNA repeat and that involves cognitive impairment and behavioral changes. Molecular pathogenesis is driven by the nuclear accumulation of RNA foci, which sequester RNA-binding proteins that regulate splicing, polyadenylation and subcellular localization of downstream transcripts. However, we do not know the cell populations, molecular pathways and cell-cell interactions primarily affected in the brain. A critical question to develop effective molecular therapies. My host laboratory developed a unique mouse model of DM1 that mirrors the spatiotemporal expression of toxic RNA and relevant brain phenotypes. Using these mice, I will fill three knowledge gaps:(1) I will employ advanced spatial transcriptomics to unravel the vulnerability of diverse cell types throughout brain development and aging;(2) I will use the TRAP technology to uncover subcellular transcriptomic abnormalities in specialized neuron-astrocyte contacts and identify pivotal disease intermediates of neuroglial miscommunication;(3) I will use my expertise in AAV-mediated brain gene delivery to test the capacity of engineered protein decoys, developed in my host laboratory, to release the RNA-binding proteins sequestered in brain cells and correct the behavioral, molecular neurobiological deficit in DM1 mice. Through the integration of cutting-edge transcriptomics with a new focus on synaptic neuroglial communication, I will elucidate DM1 brain pathogenesis with unprecedented spatiotemporal resolution, and offer a framework to understand other conditions mediated by toxic RNA repeats, for which DM1 serves as a paradigm. Simultaneously, my project will enhance our understanding of RNA biology in the brain. ver más
31/03/2027
INSERM
196K€
Perfil tecnológico estimado
Duración del proyecto: 35 meses Fecha Inicio: 2024-04-23
Fecha Fin: 2027-03-31

Línea de financiación: concedida

El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-04-23
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
HORIZON-MSCA-2023-PF-01-01: MSCA Postdoctoral Fellowships 2023
Cerrada hace 1 año
Presupuesto El presupuesto total del proyecto asciende a 196K€
Líder del proyecto
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHER... No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5