Topic: Directed evolution

Develop high-throughput methods to measure how protein interactions respond to mechanical force. The project combines protein engineering, yeast surface display, directed evolution, deep sequencing and single-molecule force measurements, with machine-learning models trained on the resulting data. Initial applications study interactions involved in blood clotting and von Willebrand disease. This salaried doctoral appointment spans experimental and computational work at ETH Zurich and the University of Basel, with teaching and publication duties.

Gerald Joyce explores attempts to reconstruct features of RNA-based life in the laboratory. Under the RNA world hypothesis, early organisms used RNA to store information and catalyze replication before the emergence of DNA genomes. Directed evolution has produced RNA enzymes that copy diverse templates, synthesize structured and catalytic RNAs, and amplify short templates in an RNA-catalyzed analogue of the polymerase chain reaction. A variant can make DNA from an RNA template, suggesting a possible route between RNA and DNA genomes. Joyce also describes cross-chiral enzymes that synthesize RN