Descrizione del progetto
Ereditarietà transgenerazionale delle piccole molecole di RNA
Prove recenti mettono in dubbio il concetto secondo cui il materiale genetico è l’unica base dell’ereditarietà biologica. Oltre al DNA, anche altre molecole possono essere trasmesse tra generazioni, ma il meccanismo esatto che regola tale processo non è noto. Il progetto RNAiNHERITANCE, finanziato dall’UE, è incentrato sull’ereditarietà delle piccole molecole di RNA, il cui ruolo nella regolazione genica è conosciuto. I ricercatori impiegheranno il nematode Caenorhabditis elegans come organismo modello per studiare il modo in cui le piccole molecole di RNA vengono trasmesse dalle cellule somatiche alla linea germinale e quindi alla generazione successiva. Sarà posta particolare attenzione sull’ereditarietà epigenetica dei processi evolutivi.
Obiettivo
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.
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-COG - Consolidator GrantIstituzione ospitante
75724 Paris
Francia