Area B: Modifications on Proteins

Project B03 – Dynamics and function of posttranslational protein methylation and acetylation

The methylation and acetylation of lysine residues within proteins that regulate gene expression has been shown to play a key role in various diseases and the enzymes that catalyze these modifications have therefore gained considerable interest as potential drug targets. Surprisingly little is known about the proteins that are modified, the regulation of the enzymes, the dynamics of their turnover or their functional implications. Within this project we plan to use a variety of biochemical strategies to determine the complete lysine methylome of a human cell line. We will furthermore investigate the substrate specificity of a set of putative methyltransferases by applying a combination of different in vitro and in vivo assays. In addition, we will establish MALDI imaging as a new technology to investigate the distribution of inhibitors targeting such modifying enzymes and simultaneously the corresponding histone proteoform within tissues. Finally, we aim to use MALDI imaging as a new and antibody independent way to detect, quantify and characterize modified nucleic acids in situ.