Proteins in transformation: between misfolding, condensation and aggregation

Proteins do almost all the work that keeps cells alive. To do so, proteins must fold, assemble, phase separate and interact in precisely tuned manner, using only a limited set of intermolecular interactions. Cells maintain protein health through intricate molecular machineries that tightly control levels and quality of proteins, and respond to folding errors, through triage, refolding and degradation. Intriguingly, this quality control system depends on the same fundamental interactions that dictate protein folding, phase separation and aggregation. However, a molecular understanding of the interplay between protein misfolding, phase separation and aggregation and salvage mechanisms to ultimately understand maintenance of protein structure in live cells remains one of the most significant unsolved problem in the Chemistry of Life. A new, interdisciplinary consortium of researchers in the Netherlands – FLOW – will address this challenge of defining the molecular principles underlying protein health using a unique approach across scales and complexity: from single-molecule techniques studies to whole-cell interactomics. In this focus session we will set the stage by bringing together experts in protein misfolding, protein phase separation, protein aggregation and protein quality control, to explore similarities and differences in these pathways and identify the molecular governing principles.