Preprint: We discovered phage proteins that sequester diverse immune signaling molecules, including cUMP, cCMP, and N7-cADPR The first viral sponges to inhibit Pycsar and type IV Thoeris Congrats to talented leading author Romi Hadary! Read her thread to learn more about our findings

New pre-print from Doudna lab members @erinedoherty.bsky.social & @jnoms.bsky.social ✨ Here we explore how recurrent adaptation of a single anti-defense protein fold enables evasion of distinct immune systems.

Excited to share our new preprint co-led by @jnoms.bsky.social! Here we reveal an exceptional diversity of viral 2H phosphodiesterases (PDEs) that enable immune evasion by selectively degrading oligonucleotide-based messengers. This 2H PDE fold has evolved striking substrate breath & specificity.

The beautiful, ever-expanding universe of viral proteins targeting nucleotide immune signals! Paper by @reneechang.bsky.social in @cp-molcell.bsky.social on a nucleotide sponge www.cell.com/molecular-ce... and preprint by @doudna-lab.bsky.social on viral nucleases www.biorxiv.org/content/10.1...

😮 Cool work from Sylvain Moineau #phage #phagesky www.nature.com/articles/s41...

I'm excited to announce our new biorxiv preprint, wherein we investigate the evolution of the weirdest genetic locus I've ever seen! Behold the tgr genes of the social amoeba, which mediate self/non-self discrimination during facultative multicellularity 🐅 🧵 1/ www.biorxiv.org/content/10.1...

Fantastic results from the very talented @romihadary.bsky.social et al. on viral counter-defence sponges!! 🧽🦠

We wrote a review on the free nucleotide pool as a central playground in human, bacterial, and plant immunity – now out in Nature Reviews in Immunology www.nature.com/articles/s41... Was fun to write this piece with Dina Hochhauser! Here is a thread to explain the premises 1/

Read my review with @soreklab.bsky.social on the nucleotide pool as a central playground in antiviral immunity across humans, bacteria and plants! 🧍‍♀️🦠🌿 & how viruses overcome these nucleotide-based immune mechanisms 🗡️ www.nature.com/articles/s41...

It was such a pleasure to work on this wonderful project with the talented @nitzantal.bsky.social !

Excited to finally share this work! We noticed a pair of genes - a nuclease and a protease - shuffles between antiviral systems. We show how proteolysis activates the nuclease, triggering defense in known and unknown immune contexts. tinyurl.com/2uwwy4ty

Our new preprint by @nanamikubota.bsky.social shows that P. aeruginosa, and likely many other bacteria carrying filamentous prophages (like V. parahaemolyticus), risk being exploited by these phages in a runaway process that reduces fitness of both host and virus. www.biorxiv.org/content/10.1... 🧵

We've identified a group of nucleases that can target multiple phages with hypermodified DNA, using a sensor domain present across many domains of life. We’ve even used this as a tool to find phages with hypermodified DNA! Really thankful to all the co-authors who have been such great help!

Interested in phage defenses that natively block lytic phage used in therapies? Or do you want to figure out if a phage has a modified genome? Meet the END-nucleases, an enzyme family that can broadly restrict phages with many diverse modifications. From talented post-doc Wearn-Xin Yee!

Excited to share that my first first author paper from grad school is up now at PLOS Genetics @plos.org! dx.plos.org/10.1371/jour...

Preprint alert! ✨ In this project that I co-led with @benadler.bsky.social, we show that a miniature CRISPR-Cas10-like enzyme, mCpol, uses a novel inverse signaling mechanism to prevent the spread of viruses that attempt immune evasion by depleting host cyclic nucleotides. Check it out:

Big Fantastic Virus Database (BFVD) version 2 improves 31% of predictions through 12 ColabFold recycles. PAEs and MSAs now also available for download and in the webserver. 🌐https://bfvd.foldseek.com 💾https://bfvd.steineggerlab.workers.dev/ 1/3

BFVD has been updated to version 2! Rachel improved the accuracy of viral structure predictions by running 12 recycles of ColabFold (AlphaFold2). In the latest database, over 60% of the predicted structures are now high quality. Also, we provide the PAE JSON files for each predictions.

A minimal CRISPR polymerase produces decoy cyclic nucleotides to detect phage anti-defense proteins https://www.biorxiv.org/content/10.1101/2025.03.28.646047v1

Structural basis of antiphage defense by an ATPase-associated reverse transcriptase https://www.biorxiv.org/content/10.1101/2025.03.26.645336v1

Hello BlueSky! Inaugural post here from the Sternberg Lab. We're excited to share our latest work, in which we teamed up with the @WiedenheftLab to study how DRT9 reverse transcriptases provide antiviral immunity. Here’s what we found: www.biorxiv.org/content/10.1...

Glad to share the work of @yli18smc.bsky.social and co on Lamassu, a bacterial defense system related to Rad50/Mre11 (RM). While RM carefully trims DNA ends for repair, Lamassu chops up the host chromosome. Our study reveals how it is regulated to minimize damage, activating only during infection.

Happy to share the beautiful structure of a Wadjet SMC complex by @roisnehamelinf.bsky.social, with support from the DCI and @drhonsworth.bsky.social ! This is a type II Wadjet with unique characteristics including a tandem KITE subunit, distinct coiled coil architecture and a deviant hinge.

My lab’s first preprint! We used functional metagenomics to identify phage defenses in human and soil microbiomes. We scaled these selections while maintaining accuracy, enabling us to examine 9 habitats for defense elements against 7 phages. www.biorxiv.org/content/10.1... 1/10

we recently found some really neat RNA-guided DNA-cutting systems in phages. Despite remarkable similarities to CRISPR systems, including encoding guide RNAs in arrays, they appear entirely evolutionarily distinct (but definitely related to snoRNAs 🤓) We decided to call them TIGR-Tas systems 🐯

Pseudomonads coordinate innate defense against viruses and bacteria with a single regulatory system https://www.biorxiv.org/content/10.1101/2025.02.26.640152v1

A prophage-encoded anti-phage defense system that prevents phage DNA packaging by targeting the terminase complex https://www.biorxiv.org/content/10.1101/2025.02.27.640495v1

It is finally out! Muntathar Al-Shimary, @doudna-lab.bsky.social , @cresslab.bsky.social and I present a gene knockdown tool that works in diverse bacteriophages: CRISPRi through antisense RNA Targeting (CRISPRi-ART)! Check it out @naturemicrobiol.bsky.social www.nature.com/articles/s41...

#TheMoreTheMerrier! Wu, Yan &co show @cp-immunity.bsky.social that antiviral OAS alerts neighboring cells by producing 2-5A which via gap junctions or exporter/importer activates RNaseL, protecting against infection or tumor growth! #ScienceSavesLives dlvr.it/TJB0nT

Legitmately thrilled to share our latest work, in which @fernpizza.bsky.social solved an experimental challenge in plasmid biology as old as the field: measuring how plasmids compete and evolve within individual cells!

Base-modified nucleotides mediate immune signaling in bacteria www.science.org/doi/abs/10.1... #jcampubs

New version of DefenseFinder available defensefinder.mdmlab.fr (& cli) Now encompassing 263 systems (+111 this year..!). Thanks @ftesson.bsky.social, DefenseFinder grandmaster. Full list of systems here: defense-finder-models/List_system_article.md at master · mdmparis/defense-finder-models

Check out our new study! We show that Arabidopsis uses the EDS1-SAG101-NRG1 node to trigger rapid yet contained cell death. Key finding: NRG1C variant regulates this process by competing with functional NRG1s. Amazing collaboration between Jijie Chai and Parker Labs. www.nature.com/articles/s41...

Foldseek-Multimer—now published in @naturemethods.bsky.social—our fast multimer search tool, enables complex comparisons against the full PDB in seconds. It comes with BFMD, a collection of 300K+ predictions gathered from community projects. 📄 nature.com/articles/s41... 🌐 search.foldseek.com

🚨 🧬 Updated preprint on the completed BASEL collection - what's new? Some fun with bacterial immunity and a new P22 relative infecting E. coli K-12. A thread 🧵

Happy to share our latest piece of work on the PARIS bacterial immune system. We performed a detailed characterization of the AriB Toprim nuclease, the effector of PARIS immunity. www.biorxiv.org/content/10.1...

Exciting to see our paper now published 🙌 www.science.org/doi/10.1126/... In this project co-led with @ostermanilya.bsky.social at @soreklab.bsky.social , we show that a bacterial immune system employs a TIR protein and a caspase-like protease, two typical immune components seen in eukaryotes. 🧵👇

Our paper is finally published in Science! 🎉The HPLC, NMR, MS, purification, and characterization of the new molecule felt like a real detective story. I was especially thrilled to use and reference my grandfather, Lev Osterman's, 1966 paper—he was the main reason I became a scientist.

Out today @ Science: TIR signaling activates caspase-like immunity in bacteria We report a new immune signaling molecule: N7-cADPR. Produced by phage-induced TIRs and activates a defensive bacterial caspase Congrats Francois Rousset, Ilya Osterman and coauthors! www.science.org/doi/10.1126/...

Our paper out @Nature: CARD domains mediate anti-phage defense in bacterial gasdermin systems CARDs are essential for caspase recruitment during human inflammasome activation. We now find them in bacterial immune systems Congrats Tana Wein! Thank you Kranzusch lab! www.nature.com/articles/s41...

I'm thrilled to announce our latest work is now published in Cell! Viruses encode numerous proteins that inhibit host defenses, but identifying immune-modulatory proteins among millions of viral sequences has been nearly impossible - until now! www.cell.com/cell/fulltex...

Check out our latest paper using protein structures to uncover immune inhibitors hidden among millions of phage genes! These inhibitors block immune proteins from bacteria, plants and even humans, highlighting how immunity and counter-immunity mechanisms are conserved across the tree of life! 🦠🌿🧍‍♀️

Our paper out @CellCellPress: Structure guided discovery of viral proteins that inhibit host immunity Congrats Erez Yirmiya, Azita Leavitt, Gil Amitai, our collaborators at the Kranzusch lab, and coauthors A 🧵 1/10 www.cell.com/cell/abstrac...

RNA control of reverse transcription in a diversity-generating retroelement www.nature.com/articles/s41...

What a great way to end the year! ✨ Today in @cellpress.bsky.social we report the structure and function of the Shedu anti-phage defense system. tinyurl.com/4crj6dnx A long 🧵...

A widespread family of viral sponge proteins reveals specific inhibition of nucleotide signals in anti-phage defense https://www.biorxiv.org/content/10.1101/2024.12.30.630793v1

Out in NAR, AntiDefenseFinder & our "systematic" analysis of inhibitors of antiphage systems wt Bondy-Denomy lab led by @ftesson.bsky.social and E. Huiting. Not so "systematic" as very few known, fun stuff on MGE, antidefense islands and cool phages exaptations! academic.oup.com/nar/advance-...

I’m so excited to share that some of my grad work in the @aaronwhiteley lab is now available on bioRxiv! We used an AlphaFold-multimer screen to uncover how a bacterial NLR-related proteins senses multiple phage-encoded proteins to confer phage protection. Link: www.biorxiv.org/content/10.1...

Cool! Deoxy-Inosine as new immune signaling molecules in bacteria

New insights on TIR signaling in plant immunity. The functional conservation of TIR signaling in bacterial and plant immunity is incredible