"Impact of transposable element activity on genome stability and organization during meiosis (2022-03-BOURCHIS)" project details

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General information

Application closed

2022-03-BOURCHIS

Transposable elements; Meiosis; Chromatin; DNA methylation; Genome stability; Nuclear organization

Impact of transposable element activity on genome stability and organization during meiosis

Director(s) and team

Deborah Bourc’his

Epigenetics decisions and Reproduction

Abstract

Transposable elements (TEs) are mobile genetic entities that are present by millions in mammalian genomes. Their effects are pleiotropic, from insertional mutagenesis to chromatin position effects or chromosome rearrangements. While TEs have prompted useful innovations during evolution, they constitute a genomic threat in the short term. Accordingly, cells use several strategies to tam TEs, among which DNA methylation plays a key role. Importantly, TE activity has been linked to several diseases, including cancer and infertility. Notably, our team previously showed that meiosis is particularly vulnerable to TE activity: when TEs fail to be repressed during male germline development, homologous chromosome pairing is impaired at meiosis, leading to spermatogenesis interruption and male sterility.   The project aims at deciphering the relationship between TEs and meiosis, using two unique mouse models of TE reactivation, resulting from deficient DNA methylation or from temporally controlled CRISPR-based activation. Innovative genomic, bioinformatic and microscopy approaches will be carried out to:   1)      investigate the impact of TE activity on the meiotic chromatin landscape and distribution of recombination sites, 2)      investigate the impact of TE activity on meiotic chromosome conformation 3)      control in space and time TE reactivation during meiosis.   We hope to uncover how TEs influence chromosome integrity, with broad implications for reproductive and cancer research.

Requirements to apply for the PhD thesis project

We are looking for a PhD candidate with strong motivation for basic research, and potential for independent and creative thinking. Applicants should show proof of their ability to work in different lab environments and their potential for adapting to different research topics and/or techniques (geographical and thematic/technical mobility). Background in mouse genetics and/or chromatin biology is recommended. Previous knowledge in mammalian reproduction or meiosis would be a plus, but not compulsory.