Research

We are interested in the epigenetic mechanisms that govern mammalian embryonic development. Our main focus is on transposable elements (TEs) and how these genetic parasites contribute to developmental phenotypes in health & disease.

Transposable elements (TEs) are mobile genetic elements that have invaded eukaryote genomes. Nearly half of the mammalian genome is made of TEs (A). Retrotransposons, including SINEs, LINEs and ERVs/LTRs (B) propagate in the genome by a "copy and paste" mechanism via an RNA intermediate.

Many TEs control essential physiological functions as cis-regulatory elements, non-coding RNA or protein products. Yet, their mobile nature makes TEs a source of insertional mutations, affecting gene expression and cellular processes.

The lab aims to understand how TE activation results in molecular and morphological phenotypes during mammalian embryonic development.

A. Pie chart showing the proportion coding (genes) and non-coding sequences in the human genome. B. Structure of the three families of retrotranspons. SINEs: short interspaced nuclear elements: LINEs: long interspaced nuclear elements: ERVs/LTRs: Endogenous retroviruses/ Long-terminal repeats.

Mission 🧬

We are fascinated by the mechanisms of TEs interacting with gene regulation and influencing cell state. Very little is known about how this can be applied to cell differentiation and organogenesis during mammalian development. Using in vitro and in vivo mouse models, we aim to decipher the genetic and morphogenetic events modulated by TE insertion during development.

Our lab aims to achieve the following goals to decipher how TEs contribute to mammalian embryo formation:

Characterise new mechanisms by which the epigenetic derepression of TEs leads to congenital disease
Explore the role of TEs during lineage commitment and tissue shaping
Decipher how cell-specific expression of TEs in the embryo is influenced by genomic regulation and the gene regulatory landscape
Develop new tools to systematically test the impact of TE insertion on developmental cell type and gene regulation

Approach 🧪🧫🔬

Our lab’s main approach is based on genome engineering in mouse embryonic stem cells and generation of transgenic mouse models, followed by molecular and morphological dissection of developmental phenotypes. We employ CRISPR/Cas9 technology to generate tailored stem cell and in vivo mouse models targeting specific TEs or for genome-wide screening. We combine this with high-throughput sequencing (including single-cell and long-read sequencing technologies) and imaging of mouse embryos.

Projects 🥼💻

Transposable elements causing developmental pathologies

What are the mechanisms by which TEs insertions can cause developmental pathologies? Are certain genomic loci, embryonic cells & stages more sensitive to TE insertion?

We have shown that an active MusD retrotransposon inserted in the mouse genome produces viral-like particles (VLPs) in the embryo, which can cause cell death and a developmental malformation (see Publications).

We are interested in the mechanism of VLP-mediating developmental malformation as well as deciphering new mechanisms by which TE insertion affects embryo formation.

We are establishing genetic tools to modulate TE expression & generate artificial TE insertion in mouse embryonic cells and characterise the resulting developmental, molecular, and morphological phenotype.

Mouse E10.5 embryo strained with a MusD-Gag antibody. MusD VLPs are produced in the apical ectoderm ridge of the developing limb, causing cell death and a limb malformation (Glaser at al. 2025)

Transposable elements regulation

We are interested in TEs and genome regulation at multiple levels. TE-derived sequences are often found in cis-regulatory elements (CREs), regulating gene expression in a spatio-temporal manner. We want to understand how awakening or silencing of TEs influences genome regulation during development.

We have also shown that a MusD element insertion in the vicinity of developmental genes adopts the corresponding regulatory information. TEs thus not only participate in gene expression control but also use gene regulatory landscapes. How often is this happening, and how is it linked to the expression of TEs during development?

Epigenetic silencing mechanisms safeguard the genome from the detrimental effects of TEs. We are also interested in the establishment of a repressive stage for specific families of TEs and how changes in this epigenetic silencing affect development.

Physiological roles of Transposable elements

TEs have been co-opted to serve essential functions in the early embryo as well as in the adult brain. We are investigating how TE-derived sequences can participate in embryo shaping.

If you are interested in the interplay between transposable elements and embryonic development and want to develop your own ideas (particularly for postdocs), please don't hesitate to contact us with project ideas.

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