Since the elucidation of the first protein structures in the 1950s, our understanding of protein structures and consequently their biological functions has grown exponentially. However, simultaneously it has been recognized that a significant portion of the human proteome does not form stable structures, termed Intrinsically Disordered Regions or Proteins (IDR/IDPs). These proteins exhibit a spectrum of diverse, interchanging conformations without settling into a single stable 3D structure. Our research is focused on illuminating the rules underlying the structure-function relationship of IDPs and IDRs, that is the rules underlying the switch between disordered to (partially) ordered states, either due to posttranslational modifications or due to interaction with other proteins. We strive to understand the generated (sub)structures, underlying biophysical forces, collect interaction motifs potentially regulated by this mechanism and map them in the protein interactome.

We focus on cell cycle regulatory proteins, which are abundant in disorder, posttranslational modifications and interactions. Due to their central importance for the cell state their regulation is highly fine tuned, with associated proteins being associated with diverse disease states such as cancer and neurodegeneration.  

 NMR spectroscopy is the prime technique for investigation of IDRs/IDPs, it allows to study structure and dynamic processes ranging from the picosecond to hour timescale. At the university of Zurich, we have cutting-edge instrumentation at our disposal, with NMR magnets ranging from 400 MHz to the currently highest available field, 1.2 GHz. To maximize the information content of spectral studies we actively use and develop advanced sample preparation techniques, such as selective isotope labelling (methyl labelling, segmental labelling, genetic code expansion) and utilization of different protein expression systems. Functional investigation with biochemical techniques and biophysical assays complements the structural studies.