Rotem Sorek's lab uses AI protein models to find how viruses gag bacterial immune alarms

Scientists at the Weizmann Institute of Science reported in the journal Science in March 2026 that they had discovered three previously unknown families of proteins that bacteriophages, the viruses that infect bacteria, use to switch off their hosts' immune defences. The study was led by Dr. Nitzan Tal in the laboratory of Professor Rotem Sorek in the Department of Molecular Genetics, with research students Jeremy Garb and Romi Hadary and the group of Professor Philip Kranzusch at the Dana-Farber Cancer Institute in Boston.

When a bacterium senses a phage, many of its defence systems release small signalling molecules that act as an alarm and trigger an immune response. Some phages fight back with 'sponge' proteins that bind and trap these alarm molecules before they can act. Because such proteins share little genetic sequence with one another, they are hard to find by conventional methods. The Weizmann team instead used the AI tool AlphaFold to predict the three-dimensional shapes of around 32 million phage proteins and searched for small proteins built from several identical units with deep pockets, the typical architecture of a sponge.

Of more than 120 candidates tested in the lab, the researchers identified three new families, which they named Lockin, Sequestin and Acb5. X-ray crystallography confirmed that Lockin forms a ring of six identical subunits. Sequestin was found by noticing that sponge genes often fuse together, and Acb5 turned out not only to trap the alarm molecules but also to cut them, an unexpected activity. A follow-up paper from the group in Nature Microbiology in June 2026 explored the diversity of these proteins further.

Sorek's laboratory is known for uncovering dozens of bacterial immune systems in the past decade, several of which turned out to be ancestors of components of the human innate immune system.