Researchers Unveil Method for Lifelong Protein Control in Animals

Researchers have achieved a significant breakthrough by enabling the precise control of protein levels in living animals throughout their lives. This innovative method, developed by scientists at the Center for Genomic Regulation in Barcelona and the University of Cambridge, allows for the manipulation of protein concentrations in various tissues of the model organism, the nematode worm Caenorhabditis elegans. The findings were published on December 12, 2025, in the journal Nature Communications.

This new technique offers scientists the ability to regulate protein levels with remarkable accuracy, which is crucial for investigating the biological mechanisms associated with aging and various diseases. The research team successfully demonstrated the method’s effectiveness by controlling protein amounts in the intestines and neurons of the worms.

Advancing Understanding of Aging and Disease

The implications of this research extend far beyond the laboratory. The ability to manipulate protein levels could lead to groundbreaking experiments that were previously unfeasible. For instance, researchers can now explore how varying amounts of a specific protein influence overall health. Dr. Nicholas Stroustrup, a researcher at the Center for Genomic Regulation and senior author of the study, noted, “No protein acts alone. Our new approach lets us study how multiple proteins in different tissues cooperate to control how the body functions and ages.”

Understanding systemic processes like aging requires a nuanced approach, as interactions between different organs play a critical role. Traditional experimental methods struggle to isolate the effects of proteins across various body parts. This new technique allows for a more precise, lifelong control of protein levels, shedding light on how subtle changes can impact the organism as a whole.

How the Dual-Channel AID System Works

The technique is an evolution of earlier methods drawn from plant biology, specifically the use of the hormone auxin for growth regulation. The research team adapted the auxin-inducible degron (AID) system, which tags proteins for degradation in the presence of auxin. Upon removing the hormone, the protein reappears.

By engineering different versions of the TIR1 enzyme and degrons, the researchers created a “dual-channel” AID system. This allows for fine-tuned control over protein levels in different tissues while the organism continues its normal activities. Dr. Stroustrup explained, “To unpick nuance in biology, sometimes you need half the concentration of a protein here and a quarter there. We wanted to be able to control proteins like you turn the volume up or down on a TV.”

Their innovative approach involves attaching a degron tag to the target protein and genetically modifying the worms to produce the TIR1 enzyme in specific tissues. When the worms consume food containing auxin, the plant hormone activates TIR1, which selectively removes the desired amount of the tagged protein.

The researchers also tackled a significant challenge: AID systems often fail in reproductive tissues. They adapted their system to overcome this limitation, ensuring functionality across the entire organism, including reproductive cells.

Dr. Jeremy Vicencio, a postdoctoral researcher at the Center for Genomic Regulation and co-author of the study, described the engineering process as complex. “Getting this to work was quite an engineering challenge. We had to test different combinations of synthetic switches to find the perfect pair that didn’t interfere with one another. Now that we’ve cracked it, we can control two separate proteins simultaneously with incredible precision.”

This advancement not only enhances the toolkit available to biologists but also opens new avenues for research into the intricate workings of life. The ability to manipulate proteins at will could lead to important discoveries in understanding health, disease, and the fundamental processes of aging.

Further information about this study can be found in Nature Communications, DOI: 10.1038/s41467-025-66347-x.