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SUMOylation for 48 hours prior to differentiation creates an epigenetic environment that favours adipogenesis (our unpublished data).
Aim of the project
To understand how SUMOylation rewires the chromatin landscape, we have mapped proteins associated with SUMOylated complexes using rapid immunoprecipitation and mass spectrometry of endogenous proteins (RIME). The student will leverage these data to identify and test candidate proteins through pharmacological and RNA interference approaches. Candidate proteins will be prioritised based on their enrichment in the RIME dataset, analysis of available literature, co-immunoprecipitation experiments, and proximity ligation assays.
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
RIME : https://doi.org/10.1038/nprot.2016.020
SUMOylation at a glance : https://doi.org/10.3390/molecules26040828