SFB1551 Project: R02

Project Title: Design of Fuzzy Protein–Protein Interaction Interfaces for Modulating Protein Solubility and Phase Separation

Summary: My project aims to explore the modulating influence peptide modifiers like Ubiquitin and especially the small ubiquitin-like modifiers (SUMO) have on the phase separation behavior of aggregation-prone, intrinsically disordered proteins. For this, I am testing how the attachment of these modifiers alter the multivalency of their substrates and to which degree they directly drive or inhibit further protein interactions. In a collaboration with the Gräter lab from the MPIP Mainz, we will also investigate the functional relevance of flexibility in protein interactions. Using the posttranslational modifier SUMO as a model scaffold, we will try to assess whether interaction modules containing a folded domain tethered to a flexible arm can control multivalency and thereby phase separation of intrinsically disordered domains. We will test whether targeting a small interaction module to a multimerization domain is sufficient to inhibit phase separation, and we want to examine whether these principles can be exploited to control phase separation and solubility in vitro and in cells.