New tool will accelerate research on protein aggregation-relevant diseases
Protein aggregation, an abnormal deposition of proteins, has been found in a wide variety of disorders, particularly neurodegenerative diseases. In addition to neurodegenerative diseases, some other diseases like type 2 diabetes, inherited cataracts, and some forms of atherosclerosis also involve protein aggregation. On the other hand, protein aggregation is associated with many positive cellular functions. However, a lack of quantitative and high-throughput cellular tools has hindered the research on protein aggregation.
Excitingly, researchers headed by Dr. Ahmad Khalil of Boston University have now designed a genetic tool to measure and control protein aggregates. The tool, known as yeast Transcriptional Reporting of Aggregating Proteins (yTRAP), enables the identification of genes that can cure prion aggregation in yeast cells. The study is conducted in collaboration with Massachusetts Institute of Technology, Whitehead Institute for Biomedical Research, Marquette University, and the University of Nevada. The full article "A Genetic Tool to Track Protein Aggregates and Control Prion Inheritance" can be read in the journal Cell.
The new tool has two parts: one that binds to the target protein and the other that generates a fluorescent signal to reflect aggregation within the cell. It can apply to various types of protein aggregation. In this work, Dr. Ahmad and co-workers mainly looked at yeast prions.
The prion protein is thought to be the causing agent of various neurodegenerative diseases. Prions derive from a normal body protein that becomes irreversibly misfolded, and they can induce properly folded proteins to convert into the misfolded prion form. Because of this property, prions are described as an infectious or heritable agent.
With the help of the new tool, Dr. Ahmad's team successfully measured yeast prion aggregation and identified genes that turn prions off. On the basis of the findings, they found ways to reverse the spread of prions and eliminate them from yeast cells. Besides, they also investigated yeast RNA-binding proteins (RBPs) using the tool.
Collectively, Dr. Ahmad's team developed a new tool to measure and control aggregation of proteins like prion within cells. The tool will aid in research of protein aggregation-relevant diseases.