Newby, G.A. et al. Cell 171, 966–979 (2017).

Protein aggregation can cause devastating neurodegenerative diseases, but researchers are discovering that aggregation also plays a role in normal cellular function. A lack of high-throughput, quantitative tools for protein aggregation analysis has made this phenomenon challenging to study. Newby et al. now present yTRAP (yeast transcriptional reporting of aggregating proteins), a synthetic genetic platform that tracks protein aggregation states. The solubility state of a protein of interest is coupled to a synthetic transcriptional output; when the protein is in a soluble state, a fluorescent reporter is turned on; when aggregated, the reporter is turned off. The researchers demonstrate the use of yTRAP for sensing yeast prions in live cells, for screening mutant prion libraries to find prions that prevent aggregated states, and for identifying factors that affect aggregation of RNA-binding protein.