Projet : Démêler les conséquences de l'insertion d'éléments transposables sur la structure et la fonction du génome

Transposable elements (TEs) are genomic parasites that usually coexist with the host genome. This delicate equilibrium can be broken during aging, cancer, and neurodegenerative diseases that correlate with increased TE expression. To precisely address the causes and consequences of TE activity, we must be able to follow the genome invasion by TEs, from their awakening to their stabilization in the host genome. For this purpose, a genetically tractable system that allows to follow, in real time, TE activity over many generations and adequate bioinformatical tools have been long missing. We overcame these important experimental bottlenecks by successfully establishing a Drosophila line that allows inducible transposition of endogenous retroviruses (ERVs) in the germline and by developing an in-house software to robustly detect rare ERV genomic insertions using long-read sequencing data. Based on our unique model system and using cutting-edge genome-wide approaches, our project aims to unravel the impacts of ERV insertions on the host transcriptional outputs, epigenetic changes, 3D genomic organization and phenotypes. Monitoring how TEs and their hosts solve their genetic conflicts in real-time will certainly provide outstanding discoveries on the biology of both partners and on the molecular mechanism of this equilibrium. This ambitious project will open new avenues in the understanding of the relationships between TEs and their host genome and how they contribute to proper maintenance of genome integrity.