Herwig Schüler

Affiliated to research

About me

Undergraduate studies in Frankfurt, Uppsala and Stockholm. Doctorate in cell biology from Stockholm University. Postdoctoral studies in biochemistry at New York University Medical Center. Group leader at KI since 2008 (2008 Team leader, Structural Genomics Consortium, MBB; 2011, independent group leader, MBB; 2018 BioNut). Associate Professor (docent) in structural biology 2013. Chairman for Vetenskapsrådet review panel NT-9, 2017, 2018.

Research description

Posttranslational modifications (PTMs) orchestrate many vital events in cells, including the remodeling of chromatin in gene activation and inactivation, the transcription of active genes, the repair of damaged DNA, and the interaction of proteins in cellular signaling networks. Many enzymes are involved in putting these PTM marks in the right place at the right time, and in removing them in the proper context. Specific binder domains are involved in their recognition. Because of the consequences of their actions and because they can often be inhibited by small compounds, these proteins are often targets for drug development. With small compounds that act on these proteins we can, for instance, kill cancer cells, or influence signaling processes to reach a therapeutic outcome. This requires that we understand the actions of both the target proteins and the inhibitor substances to great detail in order for the therapeutic agents to be effective and safe.

We are interested to understand to atomic detail how the PTM ADP-ribosylation functions. For that, we study the 3-dimensional structures of PARP and related enzymes with ADP-ribosyltransferase activity, and determine their enzymatic properties. We also collaborate with chemists to develop more portent and more selective PARP inhibitors. We study the binder domains that recognize ADP-ribosylation marks in the cell. Finally, we study bacterial toxins that catalyze the same reaction, with the aim to devise novel anti-infectives.