Vojislav Gligorovski | Birnstiel Award 2025

"In vivo directed evolution of switchable proteins." Vojislav Gligorovski, EPFL Supervisor: Sahand Jamal Rahi Dynamic proteins that switch between functional states are vital for cellular processes, research, and therapy, but are difficult to design or evolve using existing methods. Vojislav Gligorovski devised a method for continuous in vivo evolution to optimize the properties of switchable proteins. The system was implemented in budding yeast by rewiring the cell cycle, making oscillations of a cyclin essential for cell survival. This design enabled selection for both “on” and “off” states of target proteins once per cell cycle. Moreover, selection pressure in this system was encoded by light, allowing precise temporal control. Applications of the system to optimize three important molecular tools: blue-light-responsive transcription factor, red-responsive protein-protein dimerization pair, and the doxycycline-inducible Tet-on system, uncovered new and unexpected evolutionary solutions. This research opens up new avenues for designing switchable proteins for research and therapeutic purposes. Vojislav Gligorovski studied molecular biology at the University of Belgrade (Serbia), before moving to Switzerland for his doctoral research at the École Polytechnique Fédérale de Lausanne with Sahand Jamal Rahi. He was the top graduate of his class in Belgrade and received Serbia’s Saint Sava Award for achievements in higher education. More about the Birnstiel Award: https://www.imp.ac.at/achievements/bi...