Scientists at EPFL have developed a technique called optovolution, using light to evolve proteins that switch states, sense environments, and perform computations. By engineering yeast cells to survive only if proteins behave dynamically, the method selects optimal variants rapidly. The approach, published in Cell, advances synthetic biology and optogenetics.
Evolution in nature shapes biological systems through selection of effective variations in DNA, RNA, and proteins. Humans have long influenced this process, from selective breeding in agriculture to modern directed evolution in labs, which improves proteins like enzymes and antibodies for medicine and industry.
Traditional directed evolution applies constant pressure, favoring proteins active all the time. This overlooks the dynamic needs of many proteins, which act as switches or logic gates responding to changing conditions. Such methods often degrade switching abilities, complicating the creation of multi-state proteins.
To address this, Sahand Jamal Rahi and colleagues at EPFL's Laboratory of the Physics of Biological Systems introduced optovolution. Published in Cell on March 9, 2026, the study details how light steers protein evolution for dynamic functions. Using budding yeast Saccharomyces cerevisiae, researchers redesigned the cell cycle so division depends on a protein's ability to switch between active and inactive states.
A regulator tied to the protein controls the cycle: essential in one phase but toxic in another. Proteins failing to switch correctly stall or kill the cell. Optogenetics delivers timed light pulses to alternate states, with each 90-minute cycle testing performance. Successful proteins enable survival and reproduction, automating selection without manual intervention.
Optovolution yielded 19 variants of a light-controlled transcription factor, showing enhanced light sensitivity, lower dark activity, or green light response—challenging for warmer colors. It also evolved a red light system independent of chemical cofactors, via a mutation disabling a yeast transport protein to utilize internal molecules.
Further, the team created a transcription factor acting as a logic gate, activating genes only with simultaneous light and chemical signals. This enables proteins to sense changes, make cellular decisions, and control division, opening avenues in synthetic biology, biotechnology, and evolutionary research.
Contributors include the EPFL Laboratory of Protein and Cell Engineering, University of Bayreuth, and Lausanne University Hospital. The journal reference is Vojislav Gligorovski et al., 'Light-directed evolution of dynamic, multi-state, and computational protein functionalities,' Cell, 2026, DOI: 10.1016/j.cell.2026.02.002.
