By forcing thousands of yeast proteins to go “on strike,” Israeli scientists identified previously unknown roles in essential biological processes with findings expected to advance research on genetic diseases, cancer, and cellular energy production, according to The Press Service of Israel (TPS-IL).
Cells rely on proteins for nearly every function, but when a protein is permanently removed, cells often compensate by using alternative proteins. This makes it difficult for scientists to determine the exact role of individual proteins. To solve this challenge, researchers developed a technique that swiftly removes proteins, preventing the cell from finding replacements and allowing their direct impact to be observed.
The research was conducted at the Weizmann Institute of Science and led by doctoral student Rosario Valenti and Dr. Yotam David in the laboratory of Prof. Maya Schuldiner in the Molecular Genetics Department. Their findings were recently published in the peer-reviewed Journal of Cell Biology.
“We’ve known for a long time that yeast is a powerful model for understanding human biology, but we were still in the dark about what around 1,200 of its proteins do,” Schuldiner said. “This study gives us a unique way to crack that mystery.”
Using genetic engineering, the researchers created a system consisting of three elements: a label that marks the protein for removal, a destructive protein that degrades it, and a mediator molecule that triggers the process. They applied this system to 5,170 different yeast strains, each missing a different protein. The result was a comprehensive genetic library, allowing researchers to observe the exact effects of protein loss in real time.
One of the major findings was the identification of 220 genes crucial for maintaining mitochondrial structure, the energy-producing centers of the cell. Mitochondrial dysfunction is linked to numerous diseases, including neurodegenerative disorders and metabolic syndromes.
“Cells constantly remodel their mitochondria to meet their needs, but the mechanisms behind this are only partially understood,” Valenti explained. “By forcing these proteins into a strike, we were able to pinpoint which genes are essential for keeping mitochondria functioning properly.”
The study also uncovered previously unknown genes involved in cell division, a process that is tightly regulated and frequently disrupted in diseases like cancer. Some of these genes were found to be critical for cell survival under all conditions, yet they had never been classified as essential before.
Beyond its scientific discoveries, the research team created a digital library that is open to scientists worldwide. “Labs from around the world have already started borrowing genetic strains to study proteins whose role is still a mystery,” Schuldiner said. “We hope this library will continue to be a valuable tool for uncovering the hidden mechanisms of life.”
The practical applications of these findings are extensive. By identifying proteins essential for mitochondrial function, scientists may be able to one day develop treatments for diseases caused by defective energy production. The discovery of genes regulating cell division could contribute to cancer research, potentially leading to new therapeutic strategies.
The findings could potentially be used to improve the efficiency of yeast-based processes used in food, pharmaceuticals, and biofuel production.
