Romi Hadary

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...

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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.

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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!

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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.

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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 🧽.

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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.

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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).

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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🌳⚔️

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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).

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Defense systems using small molecule signaling exist in >20% of bacteria 🦠 some are ancestors of central immune pathways in animals & plants.

Functional diversity of phage sponge proteins that sequester host immune signals Multiple bacterial immune systems, including CBASS, Thoeris, and Pycsar, employ signaling molecules that activate the immune response following phage infection. Phages counteract bacterial immune sign...

📢 Preprint out!
Together with @reneechang.bsky.social @kranzuschlab.bsky.social and the amazing @soreklab.bsky.social, we explored viral sponges to map their diversity and function.

Discovered huge diversity, including sponges that inhibit Pycsar & Type IV Thoeris!

www.biorxiv.org/content/10.1...

A widespread family of viral sponge proteins reveals specific inhibition of nucleotide signals in anti-phage defense Chang et al. discover anti-CBASS 4 (Acb4), a family of viral sponges that inhibits bacterial immunity by sequestering nucleotide immune signals. Acb4 homologs in phages that infect hosts across all ma...

Excited to share my PhD work in the @kranzuschlab.bsky.social, out now in Molecular Cell @cp-molcell.bsky.social

We discover Acb4, a new family of viral sponges that sequesters nucleotide immune signals and defines molecular features that enable ligand specificity.

www.cell.com/molecular-ce...

A widespread family of viral sponge proteins reveals specific inhibition of nucleotide signals in anti-phage defense Chang et al. discover anti-CBASS 4 (Acb4), a family of viral sponges that inhibits bacterial immunity by sequestering nucleotide immune signals. Acb4 homologs in phages that infect hosts across all ma...

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...

A beautiful and much-needed review on the role of nucleotides in immunity, congrats Dina!! 💫🧬

Amazing work led by @nitzantal.bsky.social👩🏼‍🔬, identifying new immune inhibitors using structural clues. So excited to see this out! 🧬💫