Romi Hadary

Our work on bacterial Schlafens in phage defense is out today @natmicrobiol.nature.com!

Check out the final version here:
rdcu.be/e7Bmz

We are looking for postdocs and students to expand our team! Official postings are coming soon.

Please reach out if you're interested!
#phage #phagesky #microsky

Very excited to see this work out today!

Discovering viral immune antagonists directly from predicted protein structures. 🤩 www.science.org/doi/10.1126/...

Huge thanks to the amazing collaborators! 🤗

CBASS is a cyclic nucleotide-based antiviral system in bacteria that is related to cGAS-STING signaling in animals. One of the big questions is how CBASS is activated during phage infection? We made some progress on this during my final year in the Kranzusch lab.
www.biorxiv.org/content/10.6...

After >10 years of our lab studying bacterial cGAS-like enzymes, @hobbslabutah.bsky.social finally reconstitutes viral sensing in vitro and discovers how these ancient receptors sense phage protease enzymes to detect virion assembly and activate antiviral immunity

www.biorxiv.org/content/10.6...

@nitzantal.bsky.social @romihadary.bsky.social @soreklab.bsky.social use structure prediction and in silico binding site analysis to discover viral immune evasion proteins! Exciting for our lab @reneechang.bsky.social @riveralopz.bsky.social to help with this project.
www.science.org/doi/10.1126/...

Excited to see our paper out in @science.org 🧽✨
Congrats @nitzantal.bsky.social !

Congratulations to Sonomi Yamaguchi for her paper at @nature.com. Sonomi discovered Clover defense and explained how nucleotide signals control each step of viral sensing, immune regulation, and viral restriction – named for her beautiful "four-leaf" structures 🍀

www.nature.com/articles/s41...

Excited to share our new paper led by a wonderful Jing Liu on designing de novo IDRs🧪🖥️

Chemical inhibition of a bacterial immune system Bacteriophages are promising alternatives to antibiotics for treating bacterial infections. However, bacteria possess immune systems that neutralize bacteriophages. Zang et al. discover small molecule...

Chemical inhibition of a bacterial immune system

Small molecules inhibit type II Thoeris anti-phage systems from diverse bacteria. One compound, IP6C, improves phage-therapy against P. aeruginosa & is effective against Thoeris in polymicrobial communities
www.cell.com/cell-host-mi...

Another amazing work by @ostermanilya.bsky.social! A new NAD⁺-depleting defense system and its phage antagonists, revealing an exciting bacterial–phage arms race. 🛡️⚔️ Congrats Ilya and coauthors!

N1-Methylpseudouridine directly modulates translation dynamics Nature - N1-Methylpseudouridine enhances the translation of synthetic mRNAs, independently of innate immunity.

Our new paper is out in Nature 🎉. We show that m1Ψ in mRNA vaccines doesn’t just quiet immunity, it also directly enhance translation by reshaping ribosome dynamics in a sequence-dependent way 🧬
Full paper : rdcu.be/eY5gx

This scientist found a new trick of the immune system by digging through cellular rubbish Nature - Yifat Merbl is part of Nature’s 10, a list of people who shaped science in 2025.

“Up ’till now, we couldn’t detect it, because we didn’t look at the garbage cans of cells.”

Yifat Merbl found a new trick of the immune system, and is part of Nature’s 10, a list of people who shaped science in 2025

go.nature.com/3XZQdgY

Environment and physiology shape antiphage system expression Bacteria and archaea encode on average ten antiphage systems. Quorum sensing, cellular, or transcription factors can regulate specific systems (CRISPR-Cas, CBASS). Yet, a systematic assessment of anti...

Bacterial genomes encode a rich repertoire of antiphage systems, but we still know surprisingly little about when these systems are actually expressed.

In this preprint, Lucas Paoli et al, ask what shapes antiphage systems expression in native contexts.
www.biorxiv.org/content/10.6...

Incredible to learn how far-reaching and diverse Thoeris really is! TIRs play key roles across kingdoms, and this work beautifully highlights their bacterial origins.

Congrats @erezyirmiya.bsky.social & Azita! 👏🌟

🧬🛡️How are new immune mechanisms created?

We show how Lamassu antiphage system, originated from a DNA-repair complex and evolved into a compact and modular immune machine, wt Dinshaw Patel lab in @pnas.org.
👏 @matthieu-haudiquet.bsky.social, Arpita Chakravarti & all authors!

doi.org/10.1073/pnas...

Recurrent acquisition of nuclease-protease pairs in antiviral immunity Antiviral immune systems diversify by integrating new genes into existing pathways, creating new mechanisms of viral resistance. We identified genes encoding a predicted nuclease paired with a trypsin...

Our nuclease-protease story is out! We explored a fascinating case of coevolution and modularity in prokaryotic immune systems: www.science.org/doi/10.1126/...

Thanks to wonderful coauthors/collaborators/friends, the whole @doudna-lab.bsky.social and everyone at @innovativegenomics.bsky.social

So proud of @nitzantal.bsky.social 👏🏻such an inspiring and brilliant scientist!

An incredible story revealing a novel defense system that senses DNA shredding during phage infection — beautifully solved by @ostermanilya.bsky.social ! 🧬✨

A miniature CRISPR–Cas10 enzyme confers immunity by inhibitory signalling - Nature Panoptes, an anti-phage defence system against virus-mediated immune suppression, is revealed.

Today in @nature.com , we highlight how a cousin of CRISPR-Cas10, mCpol, establishes an evolutionary trap in anti-phage immune systems.

Check out @erinedoherty.bsky.social and my work from @doudna-lab.bsky.social lab here:
www.nature.com/articles/s41...

The Panoptes system uses decoy cyclic nucleotides to defend against phage - Nature The Panoptes antiphage system defends bacteria by detecting phage-encoded counter-defences that sequester cyclic nucleotide signals, triggering membrane disruption and highlighting a broader strategy of sensing immune evasion through second-messenger surveillance.

Our story describing the Panoptes bacterial immune defense system is now finally peer-reviewed and published today! www.nature.com/articles/s41...

Viral effectors trigger innate immunity across the tree of life | Philosophical Transactions of the Royal Society B: Biological Sciences Viruses are ubiquitous biological entities that exert immense selective pressures on their hosts, driving the evolution of diverse innate immune mechanisms across all domains of life. While innate imm...

Effector-triggered immunity (ETI) indirectly detects pathogen effector activity on the host cell.

Kevin Barthes,Tanita Wein and I examine how prokaryotic and eukaryotic viruses deploy similar effectors that activate ETI, underscoring its central role across the tree of life.

tinyurl.com/mr3a3xh2

Synthetically designed anti-defense proteins overcome barriers to bacterial transformation and phage infection Bacterial defense systems present considerable barriers to both phage infection and plasmid transformation. These systems target mobile genetic elements, limiting the efficacy of bacteriophage-based t...

📢 New preprint alert!
We designed synthetic proteins that can block bacterial immune systems, allowing phages + plasmids to overcome natural defenses.
This could transform phage therapy + genetic engineering.
Here’s what we found 🧵
Preprint🔗: www.biorxiv.org/content/10.1...

9/
It was such a fun & inspiring journey🎉 Huge thanks to @reneechang.bsky.social- it was a pleasure working on this together! Special thanks to all amazing contributors Nathalie Bechon, @nitzantal.bsky.social, @ostermanilya.bsky.social, @erezyirmiya.bsky.social, Jeremy Garb, @amitaig.bsky.social.

8/
Remarkably, 65 sponges inhibit ≥1 immune system, and 25 block multiple 🧬. They evolved specificity & diversity, a striking example of the phage–bacteria arms race ⚔️. Sponges appear key for phages, shaping many bacteria–virus interactions, and new families keep being discovered!

7/
Tad2 homologs that bind N7-cADPR 🧽, neutralizing Type IV Thoeris — the first anti-defense protein discovered for this system. Evidence for this novel function was collected both in vivo using multiple infection assays and in vitro with biochemical experiments.

6/
We found the first Pycsar-targeting sponges, from the Tad2 family! Using mutation analysis, we showed that MoTad2 binds Pycsar molecules in a pocket distinct from its Type II Thoeris target 🧽.

5/
We discovered 10 Acb2 homologs that inhibit Type I Thoeris! A new function for this family 🌟 One was crystallized bound to its target molecule 3′cADPR, thanks to the expertise of @reneechang.bsky.social — revealing how this sponge works.

4/
84 homologs were screened experimentally against 7 immune systems, including different types of Thoeris, CBASS & Pycsar — using a high-throughput 96-well infection assay 🧪 (developed with @nitzantal.bsky.social & Jeremy Garb).

3/
A few homologs from each family already showed intriguing diversity in specificity to signals, which made us excited to systematically explore the full range of sponge diversity.
We collected thousands of Tad1, Tad2 & Acb2 homologs, built phylogenetic trees, and tested representatives' function🌳⚔️

2/
Phages must fight back! ⚔️
Sponges 🧽 are viral proteins that bind signaling molecules, preventing activation of defenses. The first families discovered were Tad1 & Tad2 (anti-Thoeris & CBASS) and Acb2 (anti-CBASS).