Descripción del proyecto
¿Cómo configura el paisaje regulador tridimensional la evolución de la determinación del sexo?
Todas las células de un organismo vivo heredan un genoma completo, que contiene un conjunto íntegro de genes. Sin embargo, las células solo expresarán aquellos genes que sean pertinentes para alcanzar su estado diferenciado y formar tejidos asociados. Cuándo, dónde y cuántos genes se expresan está controlado por paisajes reguladores tridimensionales (3D), que resultan de una interacción entre genes, elementos reguladores y la organización 3D de la cromatina. Hasta el momento, aún no se ha estudiado en detalle la forma en que los paisajes reguladores 3D influyen en la evolución de los programas del desarrollo. El equipo del proyecto 3D-REVOLUTION, financiado con fondos europeos, aprovechará los últimos avances tecnológicos para investigar este aspecto utilizando como modelo la determinación del sexo gonadal en tetrápodos.
Objetivo
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.
Ámbito científico
Palabras clave
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
HORIZON-ERC - HORIZON ERC GrantsInstitución de acogida
28006 Madrid
España