The epigenetic role of Polycomb-protein EZH2 in pancreatic

Lead Research Organisation: Babraham Institute
Department Name: Epigenetics


The Rugg-Gunn group, in partnership with DefiniGEN, have been awarded a 4-year MRC industry CASE Studentship to investigate the role of epigenetic mechanisms in human pluripotent stem cell differentiation.

Production of pancreatic beta cells is a major objective of regenerative medicine. One promising source of beta cells is through generation from human pluripotent stem cells (hPSC). The non-academic partner of the project, DefiniGEN, are world leaders in producing pancreatic cell types from hPSC. Their technology platform pushes hPSC through sequential cell fate choices that mimic normal developmental processes, ultimately leading to endocrine cells including glucose-responsive insulin-secreting beta cells. Current research challenges include identifying strategies to increase efficiency at each stage of differentiation, and optimise the final steps required to mature the endocrine cells into fully functional hormone-secreting cell types.

Trimethylation of histone H3 at lysine 27 (H3K27me3) is catalysed by the Polycomb-protein EZH2, and is associated with the transcriptional repression of genes that encode key developmental regulators. Evidence shows that changes in H3K27me3 are instructive in coordinating cell fate decisions during pancreatic development and beta cell formation in mice. A detailed analysis of the role of EZH2 in human pancreatic development has not been investigated. We will therefore test the hypothesis that EZH2 provides a system of transcriptional repression to control each stage of human pancreatic differentiation.

This project will use epigenomic and transcriptomic profiling to define the role of EZH2 in regulating human pancreatic development, and genetic approaches to test whether loss of EZH2 function and associated histone mark at selected stages of differentiation can improve the yield and maturity of beta cell production from hPSC.

Project training
The student will join the Rugg-Gunn lab within the Epigenetics ISP (6 groups, ~40 researchers), and a Graduate Programme of 50-60 highly motivated students. S/he will be fully trained in all techniques required for this project, in particular hPSC culture and manipulation and advanced differentiation assays, genome-wide histone modification profiling by ChIP-seq and transcriptional profiling by RNA-seq, bioinformatics data analysis, and a broad range of routine and specialist molecular techniques, all supported by state-of-the-art facilities at Babraham. The student will spend 6 months period of time working within the laboratories of DefiniGEN at their Babraham Research Campus location, providing exposure to all aspects of working in a commercial company.


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Studentship Projects

Project Reference Relationship Related To Start End Student Name
MR/N018419/1 01/10/2016 30/03/2021
1803334 Studentship MR/N018419/1 01/10/2016 30/09/2020