Projektbeschreibung
Wie prägen dreidimensionale regulatorische Landschaften die Evolution der Geschlechtsbestimmung?
Alle Zellen eines lebenden Organismus erben ein vollständiges Genom, das einen vollständigen Satz aller Gene enthält. Zellen werden jedoch nur die Gene verwenden, die relevant sind, um ihren differenzierten Status zu erreichen und assoziierte Gewebe zu bilden. Wann, wo und wie viel Gene exprimiert werden, wird durch regulatorische dreidimensionale Landschaften gesteuert, die aus einem Zusammenspiel zwischen Genen, regulatorischen Elementen und dreidimensional organisiertem Chromatin resultieren. Bislang ist noch weitgehend unerforscht, wie dreidimensionale regulatorische Landschaften die Evolution der Entwicklungsprogramme beeinflussen. Das EU-finanzierte Projekt 3D-REVOLUTION wird die jüngsten technischen Fortschritte ausnutzen und diesen Aspekt untersuchen, wobei es die Geschlechtsbestimmung der Keimdrüsen bei Tetrapoden als Modell verwendet.
Ziel
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.
Wissenschaftliches Gebiet
Schlüsselbegriffe
Programm/Programme
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thema/Themen
Finanzierungsplan
HORIZON-ERC - HORIZON ERC GrantsGastgebende Einrichtung
28006 Madrid
Spanien