Mass spectrometry and molecular biology of epigenetic DNA/RNA modifications

Scientific Background

The ERC-funded laboratory of Christof Niehrs studies regulatory DNA and RNA modifications, which play important roles in development & disease. We utilize highly sensitive mass spectrometry (Triple Quadrupole Mass Spec) and stable isotope metabolic labelling to profile epigenetic and epitranscriptomic changes, including 5mC, 5hmC, 5fC, 5caC, m6A, and others.

The Project

The successful candidate will study nucleic acid modifying enzymes to unravel how chemical modifications in DNA, RNA and R-loops regulate pluripotency and differentiation of mammalian embryonic stem cells and embryos.

You will use mass spectrometry, genome-edited CRISPR/Cas9 stem cell mutants, as well as various NGS protocols to carry out a multi- dimensional analysis to address:

  • Which modifications can be identified and how do they change with different cellular states?
  • Where in the genome and in which RNAs do the modifications occur?
  • What are molecular determinants involved in targeting of modifications to specific sites?
  • The project will involve strong interaction with computational biologists.

For more information, see https://www.imb.de/research/niehrs/research 

Required Qualifications

  • PhD & publications in a relevant field
  • Experience in RNA-DNA biochemistry
  • Excellent communication skills and good team spirit
  • Ability to solve problems independently
  • Fluent in English (spoken and written)

Publications Relevant to the Project

(*indicates joint contribution, #indicates joint correspondence)

Musheev MU#, Baumgärtner A, Krebs L and Niehrs C#  (2020) The origin of genomic N6-methyl-deoxyadenosine in mammalian cells. Nat Chem Biol, 16:630–634

Leismann J*, Spagnuolo M*, Pradhan M, Wacheul L, Vu MA, Musheev M, Mier P, Andrade-Navarro MA, Graille M, Niehrs C, Lafontaine DLJ# and Roignant JY# (2020) The 18S ribosomal RNA m6A methyltransferase Mettl5 is required for normal walking behavior in Drosophila. EMBO Rep, 21:e49443

Arab K, Karaulanov E, Musheev M, Trnka P, Schäfer A, Grummt I# and Niehrs C# (2019) GADD45A binds R-loops and recruits TET1 to CpG island promoters. Nat Genet, 51:217–223

 

More Details

Prof. Christof Niehrs

Research website