Descrizione del progetto
In che modo i panorami normativi tridimensionali plasmano l’evoluzione della determinazione del sesso?
Tutte le cellule di un organismo vivente ereditano un genoma completo, contenente una serie completa di geni. Tuttavia, le cellule useranno solo quei geni rilevanti per raggiungere il proprio status differenziato e formare tessuti correlati. Quando, dove e quanti geni vengono espressi sono aspetti regolati dai panorami normativi tridimensionali, che derivano da un’interazione tra geni, fattori normativi e organizzazione tridimensionale della cromatina. A tutt’oggi sappiamo ancora poco su come i panorami normativi influiscono sull’evoluzione dei programmi di sviluppo. Avvalendosi dei recenti progressi tecnologici, il programma 3D-REVOLUTION, finanziato dall’UE, approfondirà questo aspetto usando come modello la determinazione gonadica del sesso nei tetrapodi.
Obiettivo
Vertebrate genomes are organized in 3D regulatory landscapes that control pleiotropic gene expression. Within them, transcription emerges from a precise interplay between genes, regulatory elements and 3D chromatin organization. We and others have shown how mutations in these regulatory layers can modulate phenotypes. However, how 3D regulatory landscapes shape the evolutionary history of developmental programs is still largely unexplored.
Our limited capability to read, interpret and modify genomes has constrained our knowledge on how gene regulation evolves. However, recent advances in long-range sequencing, single-cell, chromatin interaction and genome editing methods offer novel tools to link genomic variation and phenotypes. Here, I will combine these methods to investigate how changes in 3D regulatory landscapes contribute to refine the function of developmental programs. As a testbed, I will study gonadal sex determination, an essential process for species perpetuation but characterized by a remarkable evolutionary plasticity.
We will use single-cell transcriptomics across tetrapod clades to unravel the core and variable transcriptional network of sex determination. Single-cell epigenomics and novel chromatin interaction methods will reconstruct 3D regulatory landscapes and infer sources of regulatory variation. With phylogenomic comparative strategies, we will estimate the contribution of different types of mutations to different sex determination programmes, as well as the impact of whole genome duplications. Finally, we will develop innovative transgenic methods for inter-species replacement of 3D regulatory landscapes, using this technology to activate early estrogen synthesis in mouse.
3D-REVOLUTION will provide ground-breaking insights on the evolution of gene regulation. This will improve our understanding of the genomic sources and underlying mechanisms of phenotypical variation, which are relevant for developmental and evolutionary genetics.
Campo scientifico
Parole chiave
Programma(i)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Argomento(i)
Meccanismo di finanziamento
HORIZON-ERC - HORIZON ERC GrantsIstituzione ospitante
28006 Madrid
Spagna