📢 Preprint out! Together with @reneechang and the amazing @SorekLab , we explored viral sponges to map their diversity and function. Discovered huge diversity, including sponges that inhibit Pycsar & Type IV Thoeris! https://t.co/ZhHMK7KB6O

📢Preprint out! Excited to share my final work from the @Soreklab! We mined phage dark matter using structural features shared by anti-defense proteins (viral tools that help phages bypass bacterial immunity) to guide discovery. Found 3 new families targeting immune signaling!

Genomes encode biological complexity, which is determined by combinations of DNA mutations across millions of bases In new @arcinstitute work, we report the discovery and engineering of the first programmable DNA recombinases capable of megabase-scale human genome rearrangement

Excited to share our latest on the Type II Thoeris system! In collaboration with the Sorek and Kranzusch labs, we identify His-ADPR as a signaling molecule. Huge thanks to all involved—amazing teamwork! https://t.co/PbEQ4ZHKyl

🗓️Tomorrow! Ariel Cohen, VP Development Projects will present "The Challenges & Opportunities of the Development Pathway for Phage Therapy" 🦠at the Antimicrobial Chemotherapy Conference 2025, join virtually 14:35 CET! Register👉 https://t.co/n29t3rQtKo #PhageTherapy #Antibiotics

Another cADPR isomer involved in bacterial immunity has been discovered. For me, N7 was the least expected position; I was sure it would be N3, but no... So, there are two more positions for cyclization that should be discovered: N3 and -NH2. More Thoeris systems are waiting! :)

Congrats our very own @Sys_Immunology member PI @TanaWein for the impressive new paper @Nature together with @SorekLab- Shedding yet another piece of the (inflammasome-related) origins of immunology in bacteria!! Proud of you Tana and team! https://t.co/jQs7rpljnY

Now published @ScienceMagazine: TIR signaling activates caspase-like immunity in bacteria We report a new immune molecule: N7-cADPR. Produced by phage-induced TIRs and activates a defensive bacterial caspase Congrats @FrancoisRousset & @IlyaOsterman! https://t.co/cgGFIUqSLZ

We just posted a new preprint where we found retrons in bacteria out in the real world, in dirt and water. We describe the first retrons in a handful of new species, show how they defend against phages, and use them to edit genomes. Read about it here: https://t.co/DiZmZOWCGs

Read more about our discovery in the thread by lead author @TanaWein 👇 https://t.co/7EYlUlvZL2

Our paper out @Nature: CARD domains mediate anti-phage defense in bacterial gasdermin systems CARDs are essential for caspase recruitment in inflammasome activation. We now find them in bacterial immune systems Congrats @TanaWein! Thanks Kranzusch lab! https://t.co/yWUj5ZMjjO

Congrats to all coauthors and especially to talented Erez Yirmiya @ErezTzvi , who had the vision to use AF for immune modulation research already since 2021, when AF was just released for public use Read Erez' thread for more details on our discoveries: https://t.co/ppHRGlCQ2W

Our results demonstrate that phage genomes are a reservoir for immune modulating proteins capable of inhibiting bacterial, animal and plant immunity 9/10

The anti-CBASS protein we found, called Acb3, inhibits diverse bacterial cGAS-like proteins via extensive interactions that include the active site Acb3 also inhibits the activity of human cGAS, binding residues conserved between the human and bacterial homologs 8/10

Remarkably, we found that Tad4, a phage-encoded anti-Thoeris protein, can also bind and inhibit the plant immune TIR protein BdTIR, as well as the TIR domain of human SARM1 Conservation of TIRs across bacteria, plants and humans leads to conservation of anti-TIR as well 7/10

All TIR binders inhibit TIR activity by making direct contacts with the catalytic residue of the TIR active site 6/10

We found six families of Thoeris inhibitors and one family of cGAS inhibitors, overall encoded in thousands of phages Crystal strx of a complex between Thoeris TIR and one inhibitor (thank you Kranzusch lab!) completely matched AF prediction (strx in color, prediction grey) 5/10

Phage proteins that received high-confidence AF scores for binding an immune protein were tested experimentally - to see if they can inhibit immunity in vivo and in vitro 4/10

Here we focused on Thoeris and CBASS, two bacterial immune systems that are the ancestors of eukaryotic TIR and cGAS-STING immunity We clustered 32M phage proteins, selected 38,700 cluster representatives, and used AF to co-fold each of them with bacterial immune proteins 3/10

Many uncharacterized proteins in the viral protein universe are thought to function in host immune inhibition Using Alphafold (AF), we can now sift through millions of viral proteins for those that bind and inhibit immune proteins 2/10