Laboratory Juliane Glaser

Transposable elements in mammalian development

Our Lab is interested in the epigenetic mechanisms that govern mammalian embryonic development. Our main focus is on transposable elements (TEs) and how those genetic parasites contribute to both pathologic and healthy developmental phenotypes. 

About half of the human genome is made of TEs. Many have been co-opted as cis-regulatory elements, non-coding RNA, or protein products driving physiological functions. Yet, their mobile nature makes TEs a source of insertional mutations, affecting gene expression and cellular processes. Epigenetic silencing mechanisms safeguard the genome from these detrimental effects. The Lab aims to understand how variation in the epigenome of TEs results in molecular and morphological phenotypes during embryonic development.

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 investigate the genetic and morphogenetic events modulated by TE insertion during development.

Goals

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

• Characterizing new mechanisms by which the epigenetic de-repression of TEs leads to congenital disease.
• Exploring the role of TEs during lineage commitment and tissue shaping.
• Deciphering how cell-specific expression of TEs in the embryo is influenced by genomic regulation and the gene regulatory landscape.
• Developing 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 the 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. 

Impact

The formation of a functional embryo is precisely regulated by genetic and morphogenetic events. Our research aims to provide novel insights into unexplored areas of (epi)genomic regulation during development, considering TEs as an important player in genetic unsolved congenital malformation and physiological embryogenesis. Our findings on mouse models will directly impact the understanding of mammalian development with a link to disease phenotype that we will apply to human’s genomic datasets.

Selected publications