Background
Obesity is a complex disease characterised by the excessive accumulation of adipose tissue and a diminished capacity to handle surplus fatty acids from the diet. The principal cell type within adipose tissue is the adipocyte, which stores fatty acids and releases them when the organism requires energy. Adipocytes can be generated in vitro by applying a potent differentiation cocktail to pluripotent mesenchymal stem cells, a process known as adipogenesis. We have shown that SUMOylation, a post-translational modification, remodels the epigenetic landscape to repress adipogenesis. Notably, inhibiting SUMOylation for 48 hours prior to differentiation creates an epigenetic environment that favours adipogenesis. Our data unpublished data suggest an epigenetic mechanism involving DNA methylation.
Aim of the project
To understand how SUMOylation regulates DNA methylation during adipogenesis genome-wide, the student will perform EM-seq experiments during adipocyte differentiation in presence or absence of a small-molecule SUMOylation inhibitor. After sequencing of the samples, the student will analyse the results using bioinformatics and statistical tools to reveal the dynamics of DNA methylation during normal adipogenesis and the effect of SUMOylation inhibition.
About the group
Our group investigates the regulation of chromatin, epigenetics, and gene expression by the small ubiquitin-like modifier SUMO during cellular differentiation. Using mouse cellular systems, we have demonstrated that chromatin-bound SUMO supports transcription during adipocyte differentiation. In addition, we have shown that SUMO regulates human adipocyte identity and metabolism.
If you are interested in this project, please contact the main supervisor.
Relevant literature
Molecular mechanisms of adipogenesis: https://doi.org/10.1038/s41580-021-00357-7
Effect of SUMOylation inhibition on adipogenesis and adipocyte identity:https://academic.oup.com/nar/article/54/6/gkag232/8528805
https://academic.oup.com/nar/article/50/3/1351/6517949
https://www.nature.com/articles/s41467-025-62361-1
EM-seq : https://pmc.ncbi.nlm.nih.gov/articles/PMC8256858/
SUMOylation at a glance : https://doi.org/10.3390/molecules26040828