MOMENTS
Financiado
Dissecting the molecular mechanisms of transgenerational epigenetic inheritance
Small RNAs have a remarkable regulatory role in most eukaryotes. These molecules bind to Argonaute proteins (AGO) and form a complex that recognizes its mRNA targets by sequence complementarity. The regulatory role is driven by th...
Small RNAs have a remarkable regulatory role in most eukaryotes. These molecules bind to Argonaute proteins (AGO) and form a complex that recognizes its mRNA targets by sequence complementarity. The regulatory role is driven by the catalytic activity of AGO, but not exclusively. In several organisms, AGO recruits other factors to perform the silencing. Remarkably, during transcriptional gene silencing, the small RNA-AGO complex engages factors that interfere with transcription but also proteins that modify the DNA and the chromatin at the targeted loci. This phenomenon has been observed in plants, yeast, flies, and worms. Particularly, in the nematode Caenorhabditis elegans, this silencing regulation can be triggered and inherited by the next generations. This reveals the importance of small RNAs and chromatin modifications for transmitting non-genetic information and maintaining germline stability across generations.
Several factors required for epigenetic inheritance have been identified by genetic screens in the worms. The nuclear Argonaute, HRDE-1, is expressed in the gonad and is a key component of this pathway. Still, what are the HRDE-1-associated factors required for transgenerational transcriptional silencing are not fully understood. This proposal aims to address what are the factors participating in the different stages of silencing mediated by HRDE-1: establishment, inheritance, and maintenance. To answer these questions, I will employ strains that allow the inducible depletion of the factors involved in the silencing response. I will combine these tools with encompassing genomics and proteomic approaches to investigate the changes across generations.
This proposal will unveil the molecular mechanisms of transgenerational epigenetic inheritance. Moreover, this study will be instrumental for the study of these responses in other organisms, especially other nematodes, with potential applications to health and ecology.
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Duración del proyecto: 24 meses
Fecha Inicio: 2023-03-09
Fecha Fin: 2025-03-31
Fecha Fin: 2025-03-31
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-03-09
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
HORIZON-MSCA-2022-PF-01-01:
MSCA Postdoctoral Fellowships 2022
Cerrada
hace 2 años
Presupuesto
El presupuesto total del proyecto asciende a
196K€
Líder del proyecto
INSTITUT PASTEUR
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5