Genetic Tool Monitors and Manipulates Cellular Protein Aggregates

This phenomenon has been difficult to study because of a lack of quantitative and high-throughput cellular tools.

To correct this lack, investigators at the Boston University College of Engineering (MA, USA) developed a synthetic genetic tool to sense and control protein aggregation. This tool - called yTRAP for yeast Transcriptional Reporting of Aggregating Proteins - was composed of two parts: one segment attached to the protein of interest and the other produced a fluorescent signal to measure the amount of aggregation in the cell.

The investigators worked with a yeast model system. They ported in the October 19, 2017, online edition of the journal Cell that by utilizing high-throughput screens, they were able to identify prion-curing mutants and engineer “anti-prion drives” that reversed the non-Mendelian inheritance pattern of prions and eliminated them from yeast populations. They extended ther technology to yeast RNA-binding proteins (RBPs) by tracking their propensity to aggregate, searching for co-occurring aggregates, and uncovering a group of coalescing RBPs through screens enabled by the platform.

This work established a quantitative, high-throughput, and generalized technology to study and control diverse protein aggregation processes in cells.

"Protein aggregates can cause a cell to gain or lose a function," said senior author Dr. Ahmad S. Khalil, assistant professor of biomedical engineering at Boston University College of Engineering. "It could be beneficial or harmful. For example, it could allow a cell to survive stressful conditions or change its metabolic function to digest a different type of sugar. And the discovery of these beneficial functions has often been serendipitous."

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Boston University College of Engineering