About the Project
While previous work has resulted in substantial advances, we still have an incomplete understanding of the pathways by which TET catalytic activity shape the DNA methylation landscape. This 4-year PhD project will investigate questions relating to both passive and active DNA demethylation through the TET-mediated generation of 5hmC, 5fC and 5caC in the genome. We will employ new molecular and biochemical approaches to identify proteins with enzymatic activity towards the modified bases and investigate their relevance in stem cells and model systems of human diseases. At the completion of this project, the PhD candidate is expected to have obtained a strong skill set in biochemistry, epigenetics and proteomics.
The research will be undertaken in the Rasmussen lab at the Centre for Gene Regulation & Expression (GRE) in the School of Life Sciences. The applicant will also work with the second supervisor Satpal Virdee in the MRC protein phosphorylation and ubiquitylation unit to design and use advanced biochemical methods to analyse aspect of DNA demethylation pathways. Training for all aspects of the project will be provided from the lab and through available skills-based courses at the University of Dundee.
Rasmussen, K. D. & Helin, K. Role of TET enzymes in DNA methylation, development, and cancer. Genes Dev. 30, 733–750 (2016).
Rasmussen, K. D. et al. Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis. Genes Dev. 29, 910–922 (2015).
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