Host physiology of the intracellular humoral immune response

Antibodies and complement proteins—immune molecules best known for patrolling the space outside cells—can also fight viruses from inside the cell, and this project aims to work out exactly how. For decades, immunologists assumed that antibodies neutralised viruses only in the bloodstream or between cells. Recent work from this lab overturned that view, showing that a protein called TRIM21 grabs antibody-coated viruses that have already entered the cell’s interior and tears them apart. The team now wants to understand the molecular machinery behind that process: how TRIM21 switches from an inactive to an active form, how it decorates viral particles with ubiquitin chains to trigger destruction, and how the exposed viral genome then alerts other sensors such as RIG-I and cGAS. They also aim to identify the unknown receptor that allows complement C3 to work inside cells, and to test whether other blood proteins that bind pathogens have similar hidden intracellular roles. This is fundamental science. It redraws the map of how the immune system works, revealing an entire layer of defence that was invisible. If the mechanisms are confirmed, they could eventually inform new antiviral strategies—for example, drugs or vaccines designed to harness intracellular antibody activity—but the immediate payoff is a deeper understanding of immunity itself.