Engineering Smart Intracellular Compartments for Directing Protein Fate

Cells must decide the fate of every newly made membrane protein: fold it, insert it into membranes, or degrade it. These triage decisions shape protein homeostasis, disease susceptibility, and the yield of biologics. In this PhD, you will engineer programmable intracellular microenvironments that control this decision. By harnessing SGTA—a cytosolic holdase that naturally captures membrane proteins and aggregation prone proteins—we will design condensates that recruit deubiquitinases (DUBs), E3 ligases, or membrane targeting factors in a controlled manner. Using nanobody fusions and light-inducible modules, we will precisely tune when and where triage decisions occur. This platform will provide new rules for engineering protein fate in cells to modulate disease outcomes and will also support improved production of challenging membrane proteins. This project across two leading institutions combines synthetic biology, cell biology, biophysical methods (including cryo-EM, NMR, MST and ITC) and advanced imaging, offering exceptional training and discovery potential.