The Niehrs laboratory studies regulation of DNA methylation, which plays important roles in development & disease. We have recently demonstrated a role for long non-coding RNAs and R-loop DNA:RNA hybrids in DNA methylation (Arab et al. 2014; Arab et al. 2019). In an ERC-funded project, we now aim to elucidate the mechanisms of DNA demethylation as well as the role played by long non-coding RNAs and R-loops in its regulation. See also www.imb.de/research/niehrs/research.
The project
Candidates will make use of mouse embryonic stem cells (ESCs) to interrogate genome-wide the role of ncRNAs and R-loops in targeting GADD45a and the DNA demethylation machinery in the genome. We will use CRISPR/CAS9 mediated ESC mutants, as well as ChIP-seq, RNA-seq, bisulfite-seq to carry out multi- dimensional data analysis to address: Where in the genome does demethylation occur? What are the molecular determinants in ncRNA & Rloops involved in targeting? What are the cofactors involved? The project will involve strong interaction between the Molecular- and the Computational Biologist.
Requirements of the candidate
• PhD & publications in a relevant field
• Sound experience in molecular biology
• Familiarity with Omics techniques or –analysis, or with ncRNAs or R-loops is advantageous
• Excellent communication skills and good team spirit with the ability to solve problems independently
• Fluent in English (spoken and written)
References
Arab, A. et al. (2019) GADD45A binds R-loops and recruits TET1 to CpG island promoters Nature Genetics 2:217-223.
Schäfer A, et al. C (2018). Impaired DNA demethylation of C/EBP sites causes premature aging. Genes Dev. 32:742-762
Arab, K., et al. (2014) Long Noncoding RNA TARID Directs Demethylation and Activation of the Tumor Suppressor TCF21 via GADD45A. Mol. Cell. 55, 604-614
Niehrs, C. and Schäfer, A. (2012) Active DNA demethylation by Gadd45 and DNA repair. Trends Cell Biol. 22, 220-227
Barreto, G., Schäfer, A., Marhold, J., Stach, D., Swaminathan, S.K., Handa, V., Döderlein, G., Maltry, N., Wu, W., Lyko, F. and Niehrs, C. (2007) Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation. Nature 445, 671-675
How to apply
Please see details on the project, information on how to apply, and an online application form at www.imb.de/postdocs. IMB is an equal opportunity employer.
Starting date: 1 April 2022 or later. The deadline for applications is 25 November 2021. Interviews will take place in Mainz on 20-21 January 2022
Application webpage: http://[www.imb.de/postdocs][2]
