Living cells resemble highly organized small towns – in addition to energy production, transportation systems, and construction, cells also require efficient waste disposal. Most proteins, which shape and sustain cellular function, have only a limited half-life and must eventually be disposed of, along with defective and unwanted proteins. This vital task falls upon specialized enzymes known as ubiquitin ligases, which tag obsolete proteins for degradation, guiding them to the cellular recycling center, the proteasome. Ubiquitin, acting as molecular label, ensures the targeted proteins are efficiently processed for disposal.

Yet, cells are not always able to recognize and mark every harmful protein with ubiquitin accordingly. Many diseases such as cancer or neurodegenerative diseases like Alzheimer’s can only arise because harmful proteins accumulate in cells. This is where the research of Georg Winter’s group at CeMM comes in: with a technique called “targeted protein degradation,” harmful or otherwise unwanted proteins can be marked with ubiquitin and destroyed in the proteasome, effectively reprogramming the cell’s waste disposal system.