New Technique Allows Fine-tuning Proteins in Animal Tissues

Scientists at the Centre for Genomic Regulation in Barcelona and the University of Cambridge developed a method that allows precise, lifelong control of protein levels inside different tissues of a living animal. The new technique, demonstrated successfully in nematode worm Caenorhabditis elegans, opens up more ways to study ageing, disease, and whole-body biological coordination.

One of the limitations faced by experimental biology researchers is the inability to fine-tune the amount of protein in tissues over an animal's lifetime. They were able to delete proteins, switch off genes, but the limitation in controlling how much protein is present in tissues slowed down the research on ageing and understanding how organs influence each other at the molecular level.

Based on a plant system involving the hormone auxin, the researchers developed the auxin-inducible degron (AID) system. Through this system, the researchers tag a protein with a degron, and then an enzyme (TIR1) recognizes the tag and disrupts the protein when auxin is detected. When auxin is absent, the protein returns. This system became their basis for a more flexible version called the dual-channel AID system. They developed a new version of TIR1 and matching degron tags. Each enzyme reacts to various auxin compounds, and by placing these enzymes in different tissues, they were able to independently control the same protein in neurons and intestines.

Read more findings in Interesting Engineering and Nature Communications.