Lab focus: Ubiquitin ligase structure and function

In order to quickly react to challenges like damage to cellular components or infections, cells modify existing proteins by attaching small tags. Ubiquitin is one such tag and is attached by enzymes called E3 ubiquitin ligases.

E3 ubiquitin ligases act on very specific targets and regulate fundamental cellular processes. However, they are also linked to diseases such as inflammation, cancer, and autoimmune or neurodegenerative diseases and may thus be new targets for innovative treatment options in these conditions.

We study E3 ubiquitin ligases to understand their functions in the human body and lay the groundwork for future drug discovery.

Research interest

We are particularly interested in a family of E3 ubiquitin ligases known as the RING-between-RING (RBR) E3 ligases. RBR ligases use a distinct and tightly controlled catalytic mechanism that is different from the mechanisms of the better studied RING and HECT E3 ligases.

So far, only a few of the 14 different RBR E3 ubiquitin ligases have been intensively studied. We combine multiple techniques to comprehensively investigate these enzymes on the molecular and cellular level:

• Structural biology (X-ray crystallography and cryo-electron microscopy)
• Protein biochemistry
• Biophysics
• Cell biology
• Mass spectrometry

One of our interests is the protein HOIP, the catalytic centre of the linear ubiquitin chain assembly complex (LUBAC), a key regulator of innate immunity.

We are also interested in shedding light on some of the understudied members of the RBR E3 ligase family to understand their biological and pathophysiological functions and investigate their therapeutic potential as future drug targets.