HOst-Transposon Interactions in the MAle GErmline

Introduction

Transposable elements (TEs) are mobile DNA sequences that have massively colonized mammalian genomes. Host genomes and TEs are engaged in ambiguous trade-offs, whereby TEs can be co-opted for genomic upgrades over evolutionary timescales, but they should also be suppressed to protect genome stability and function.

Importance of Surveillance

Effective and multi-layered surveillance is primordial: TE reactivation is associated with various dysfunctional states, including infertility, ageing, cancer, or neurological disorders, involving both transposition-dependent and -independent routes. Understanding the two-way relationship between host genomes and their TE integrants is an essential and fascinating topic, with far-reaching impact on development, evolution, and disease.

Research Proposal

Here I propose to uncover and functionally challenge the molecular arrangements that genomes and TEs came upon for the sake of germline development and fertility. The germline is a highly relevant context, as this is where host-TE interests are the most conflicting, and from their outcome depend reproductive success and species fitness.

Key Questions

I will specifically question how TE transcription is transiently tolerated during germline reprogramming and whether it could be purposely used for the early germline program.

Methodology

Using the mouse model, we will deploy innovative and ambitious approaches including:

1. In vivo epigenome editing of TE activity
2. Single-cell multimodal profiling
3. Advanced molecular profiling and microscopy

Research Objectives

We aim to investigate:

i) The molecular bases of mutualistic relationships between germ cells and TEs,
ii) The dynamic coordination of host-TE interactions within germ cell nuclei,
iii) The consequences of dysfunctional host-TE interactions on meiosis.

Expected Outcomes

By harnessing our unique expertise and tools and by going beyond correlations, we expect to reveal groundbreaking insights into the molecular transactions in which TEs and host genomes are engaged, and how unbalanced host-TE interactions can lead to disease.