Researchers Create Tool to Measure, Control Protein Aggregation


Source: Boston University College of Engineering

Summary: A team of researchers have built and described a new synthetic genetic tool which can quantitatively sense, measure and manipulate the process of protein aggregation in live cells.


In some unlinked disorders like Alzheimer’s disease and type-II diabetes there is a common thread ties them together. This thread is nothing but the protein aggregation which happens when proteins clump together. These complexes are a characteristic of many diseases but recently have found to be beneficial too. Even though protein aggregation is very common and prevalent, many of its causes and consequences are unknown. This is because there is no simple, standardized research tool to study the protein aggregation phenomenon in live cells. Researchers have built a synthetic genetic tool called yTRAP (yeast Transcriptional Reporting of Aggregating Proteins) which can quantitatively sense, measure and manipulate the process of protein aggregation in live cells. The study was published in the journal Cell.

yeast Transcriptional Reporting of Aggregating Proteins

yTRAP can be used to create cellular sensors for protein aggregation. The sensor produces fluorescent signals that depend on the protein aggregation state in the cell. In this experiment, three cell types were tested that produce varying signal strength depending on the aggregation of a prion protein. The brightest green for no prion aggregation (bottom), a slightly dimmer green to show a weak presence of prion aggregation (top right) and an even dimmer green signal for a strong prion presence (top left). Credit: Ahmad S. Khalil

yTRAP can be used to study various protein aggregation processes in disease-relevant proteins, RNA-binding proteins and prions. The tool is made of  2 parts – one piece connects to the protein of interest and another part generates of fluorescent signal to measure the quantity of aggregation in a cell. The parts can be customized to study different proteins. yTRAP can help researchers to discover to new protein aggregates and track their complex behaviors. Although the tool yTRAP is developed and tested in yeast it allows the researchers to develop treatments for the present incurable neurodegenerative diseases in humans.

Asst. Prof. Ahmed S. Khalil said, “Protein aggregates can cause a cell to gain or lose a function”, “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.”


More Information: Gregory A. Newby et al. “A Genetic Tool to Track Protein Aggregates and Control Prion Inheritance”, Cell (2017). DOI: http://dx.doi.org/10.1016/j.cell.2017.09.041


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