'Trim-Away': Targeted Degradation of Proteins & Pathogens

A protein called TRIM21 acts as a cellular bouncer, grabbing viruses that slip inside human cells and tagging them for destruction. The problem is that scientists do not fully understand how TRIM21 coordinates this antiviral response—specifically, how it builds the molecular “kill tags” (ubiquitin chains) that mark viruses for degradation, and how it simultaneously sounds the alarm to rally the immune system. This project aims to fill that gap by dissecting the precise machinery TRIM21 uses. The researchers will deploy their own invention, Trim-Away, a technique that can delete specific proteins from living cells, to identify which enzymes help TRIM21 assemble different types of ubiquitin chains. They will also investigate how TRIM21 boosts antigen presentation—a process that trains killer T cells to recognise infected cells—during infections with LCMV, influenza, and SARS-CoV-2. This is fundamental science. It will not produce a new drug or vaccine tomorrow. But understanding how TRIM21 naturally dismantles viruses and triggers immunity could eventually inform the design of antiviral therapies or vaccine adjuvants that mimic this potent cellular defence. Past discoveries about similar immune sensors have already led to new classes of drugs.