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Somatic and Germline Mechanisms of Small RNA Inheritance

Projektbeschreibung

Transgenerationale Vererbung kleiner RNA-Moleküle

Jüngste Erkenntnisse stellen die These in Frage, dass das genetische Material die einzige Grundlage biologischer Vererbung ist. Neben der DNA können auch andere Moleküle über Generationen hinweg vererbt werden, allerdings ist der genaue Mechanismus unbekannt. Das EU-finanzierte Projekt RNAiNHERITANCE konzentriert sich auf die Vererbung kleiner RNA-Moleküle, von denen bekannt ist, dass sie eine Rolle bei der Genregulation spielen. Am Modellorganismus Caenorhabditis elegans wird das Forschungsteam untersuchen, wie kleine RNA-Moleküle von somatischen Zellen an die Keimbahn und damit an die nächste Generation weitergegeben werden. Besonderes Augenmerk gilt dabei der epigenetischen Vererbung von Entwicklungsprozessen.

Ziel

Inherited information is transmitted to progeny primarily via the genome through the gametes. In recent years, epigenetic inheritance has been demonstrated in several organisms, including animals. Yet, the molecules and mechanisms responsible for this type of inheritance are incompletely understood. Histone modifications, DNA methylation, and small RNAs have been proposed to participate in epigenetic inheritance. Indeed, we recently showed how the inheritance of a specific type of small RNA impairs animals’ fertility. Diverse phenotypes, such as immune responses and learned behaviour, were also recently found to be controlled by heritable small RNAs. Despite these important roles for small RNAs in trait inheritance, their mechanism of action and how they are transmitted from tissues and gametes to the next generation remain unknown. The overall objective of this proposal is to discover novel factors and mechanisms that underlie epigenetic inheritance in animals. The nematode Caenorhabditis elegans is an ideal model system to study epigenetic inheritance, because of its short life cycle and the ability to minimize the effect of genetic variations. We will achieve our objective by applying genetic, genomic and biochemical tools to C. elegans, coupled with sophisticated sorting strategies developed in our laboratory. These approaches uniquely allow us to comprehensively evaluate small RNA inheritance in specific stages of development, tissues and organelles. Specifically, we will 1) elucidate how small RNAs and histone modifications regulate the inheritance of developmental programs, 2) decipher the mechanisms of small antisense RNA biogenesis and inheritance, and 3) discover the principles of soma-to-germline RNA transfer and its biological functions. Achieving our objective could radically change concepts of inheritance, and transform our understanding of the molecular pathways and mechanisms that govern epigenetic inheritance in animals.

Gastgebende Einrichtung

INSTITUT PASTEUR
Netto-EU-Beitrag
€ 1 997 150,00
Adresse
RUE DU DOCTEUR ROUX 25-28
75724 Paris
Frankreich

Auf der Karte ansehen

Region
Ile-de-France Ile-de-France Paris
Aktivitätstyp
Research Organisations
Links
Gesamtkosten
€ 1 997 150,00

Begünstigte (1)