Epigenetic modifications provide cells and organisms with remarkable plasticity. Yet, disentangling the Gordian knot of epigenetic cause and effect still remains a formidable task. As one of the first epigenetic alterations to be identified, DNA methylation represents perhaps the most studied and mechanistically best-understood modification. Revolutionary technologies now offer unprecedented opportunities for understanding the function of DNA methylation in specifying, memorizing, and modulating functional embryonic programs. These powerful tools motivate further development of novel experimental systems to integrate single-cell monitoring with flexible engineering of markers, reporters, and perturbations, to precisely target key rare cell populations for in-depth analysis. Building on the recent developments in single-cell genomics and epigenomics and moving forward, by developing systems for dissection of embryonic epigenetic function in-vivo, represents a deep and fundamental challenge our group is determined to engage in the coming years.
We implement cutting-edge genome- and epigenome-editing tools together with sophisticated epigenetic and gene expression reporters, utilizing embryonic stem cells and the mouse as a model organism. These state-of-the-art methodologies are implemented to address key challenges in the field, namely:
- How cell-specific methylation programs are established? How are they maintained?
- How do epigenetic changes at regulatory regions modulate target gene expression and overall cell state and function?
- What are the effects of epimutations on development and disease?
- Can environmental factors influence the germline epigenome - potentially affecting subsequent generations?