New Tool Enables Researchers to Rapidly Manipulate Protein Levels in Mammalian Cells
A research team headed by investigators at the Icahn School of Medicine at Mount Sinai (ISMMS) has developed a tool that allows scientists to quickly manipulate levels of two proteins in the same cell. They say the method, dubbed a “dual molecular tuner,” offers an easy way to perform in-depth analyses in mammalian cells in general, and stem cells in particular.
Their study, published May 27 in Nature Communications, uses two plant hormones to target specific proteins for degradation, thus allowing researchers to reduce these proteins to levels they choose. This process happens within minutes, enabling the scientists to monitor what happens in the cells as these proteins are depleted.
“We can, for example, monitor differences in cell cycle depending on how one or another protein is depleted, because this tool acts so quickly and so effectively,” says the study’s senior investigator, Ran Brosh, PhD, a postdoctoral researcher in the laboratory of the study’s corresponding author, Ihor R. Lemischka, PhD, Professor of Pharmacological Science, Developmental and Regenerative Biology at ISMMS.
Not only can researchers choose how much of one or both chosen proteins can be degraded, the entire process is reversible, Dr. Brosh says.
“Loss-of-function studies are key to understanding how genes work, but methods to rapidly and effectively disturb the function of mammalian genes — particularly stem cells — are scarce. This dual molecular tuner, in which you can manipulate two proteins independently of each other, is very useful for a wide variety of studies that have been hard to do to date, such as decoding signaling networks or protein interactions,” he says.
The tuner can be used for two proteins because researchers have identified two plant hormones that help signal the cell’s targeted destruction of the proteins being studied.
The hormones are auxin and coronatine, the bacterial analogue to the plant hormone jasmonate, both of which regulate plant physiology, but are completely non-toxic to humans — “We eat these hormones in our vegetables and salads every day,” Dr. Brosh says.
The way the system works is that researchers silence the gene or genes of interest using traditional gene silencing techniques while simultaneously delivering the same gene(s) in a form they can control. These genes now contain sequences that produce a short peptide called a degron — its function is to regulate protein degradation — that is fused to the encoded protein.
A third component that is introduced (all three contained within a single lentiviral vector) is a receptor for the plant hormone. When the cells are treated with the hormone it binds its receptor, which then targets the protein-degron fusion for destruction. “Our tuner allows a researcher to harness the cell’s degradation system, and we can turn it up or down as we wish – like dimming lights a little or all the way,” Dr. Brosh says.
Unlike other gene editing techniques, which can take months to apply to a single gene, establishment of the dual tuner takes one or two weeks of lab work, he adds.
While the tool is meant for research, it can have clinical application such as screening for drug targets, Dr. Brosh adds.
Collaborators include researchers from the University of Washington which also shares a patent with ISMMS for the development of coronatine as a research tool.
This work was supported by grants from New York State Stem Cell Science, the National Institute of General Medical Science and the Howard Hughes Medical Institute.
Competing financial interests: The authors declare no competing financial interest.
About the Mount Sinai Health System
Mount Sinai Health System is one of the nation’s leading integrated academic health systems and one of the largest in the New York metropolitan area. Its comprehensive system includes seven hospitals, more than 400 outpatient practices, over 600 research and clinical laboratories, the Icahn School of Medicine at Mount Sinai, the Graduate School of Biomedical Sciences, and the Mount Sinai Phillips School of Nursing. Together, the Health System comprises approximately 48,000 employees, more than 9,000 physicians, and 8,600 nurses.
As a leading learning health system, Mount Sinai combines clinical expertise with scientific discovery to improve patient care while training the next generation of health care and biomedical leaders. The Health System provides care across every stage of life, from prenatal care through geriatrics, while advancing personalized medicine through artificial intelligence, data science, and biomedical research.
Mount Sinai is consistently recognized among the nation’s leading academic health systems for patient care, research, and education. The Mount Sinai Hospital is ranked No. 1 in New York by Newsweek and No. 5 on the magazine’s World’s Best Hospitals list. The Icahn School of Medicine at Mount Sinai ranks No. 11 among U.S. medical schools and No. 1 among freestanding medical schools for National Institutes of Health funding, reflecting the strength of its scientific enterprise and leadership in biomedical research.
Study Helps Guide Personalized Surgical Treatment for Adolescent Idiopathic Scoliosis
Aug 19, 2026 View All Press Releases
Researchers Identify Immune Cell That Builds Cancer-Fighting Hubs Inside Tumors
Jul 16, 2026 View All Press Releases