Dina Hochhauser
@dinahoch.bsky.social
PhD student @SorekLab @WeizmannScience studying phage-bacteria interactions 🦠, MGEs 🛒 & defence islands 🛡🏝
Pinned
Dina Hochhauser
@dinahoch.bsky.social
· Jul 29
Manipulation of the nucleotide pool in human, bacterial and plant immunity - Nature Reviews Immunology
Modification of the nucleotide pool is emerging as key to innate immunity in animals, plants and bacteria. This Review explains how immune pathways conserved from bacteria to humans manipulate the nuc...
www.nature.com
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...
& how viruses overcome these nucleotide-based immune mechanisms 🗡️
www.nature.com/articles/s41...
Reposted by Dina Hochhauser
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
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
August 25, 2025 at 1:00 PM
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
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
Reposted by Dina Hochhauser
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.
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.
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.
Divergent viral phosphodiesterases for immune signaling evasion
Cyclic dinucleotides (CDNs) and other short oligonucleotides play fundamental roles in immune system activation in organisms ranging from bacteria to humans. In response, viruses use phosphodiesterase...
www.biorxiv.org
August 22, 2025 at 7:36 PM
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.
Here we explore how recurrent adaptation of a single anti-defense protein fold enables evasion of distinct immune systems.
Reposted by Dina Hochhauser
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.
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.
Divergent viral phosphodiesterases for immune signaling evasion
Cyclic dinucleotides (CDNs) and other short oligonucleotides play fundamental roles in immune system activation in organisms ranging from bacteria to humans. In response, viruses use phosphodiesterase...
www.biorxiv.org
August 22, 2025 at 7:02 PM
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.
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.
Reposted by Dina Hochhauser
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...
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 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...
www.cell.com
August 22, 2025 at 9:02 PM
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...
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...
Reposted by Dina Hochhauser
Reposted by Dina Hochhauser
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...
www.biorxiv.org/content/10.1...
Hypermutable hotspot enables the rapid evolution of self/non-self recognition genes in Dictyostelium
Cells require highly polymorphic receptors to perform accurate self/non-self recognition. In the amoeba Dicytostelium discoideum, polymorphic TgrB1 & TgrC1 proteins are used to bind sister cells and e...
www.biorxiv.org
August 5, 2025 at 12:56 AM
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...
www.biorxiv.org/content/10.1...
Fantastic results from the very talented @romihadary.bsky.social et al. on viral counter-defence sponges!! 🧽🦠
📢 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...
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...
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...
www.biorxiv.org
August 25, 2025 at 1:36 PM
Fantastic results from the very talented @romihadary.bsky.social et al. on viral counter-defence sponges!! 🧽🦠
Reposted by Dina Hochhauser
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/
www.nature.com/articles/s41...
Was fun to write this piece with Dina Hochhauser!
Here is a thread to explain the premises
1/
Manipulation of the nucleotide pool in human, bacterial and plant immunity - Nature Reviews Immunology
Modification of the nucleotide pool is emerging as key to innate immunity in animals, plants and bacteria. This Review explains how immune pathways conserved from bacteria to humans manipulate the nuc...
www.nature.com
July 30, 2025 at 6:05 AM
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/
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...
& how viruses overcome these nucleotide-based immune mechanisms 🗡️
www.nature.com/articles/s41...
Manipulation of the nucleotide pool in human, bacterial and plant immunity - Nature Reviews Immunology
Modification of the nucleotide pool is emerging as key to innate immunity in animals, plants and bacteria. This Review explains how immune pathways conserved from bacteria to humans manipulate the nuc...
www.nature.com
July 29, 2025 at 7:12 PM
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...
& 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 !
📢Preprint out!
Excited to share my final work from the @soreklab.bsky.social!
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!
Excited to share my final work from the @soreklab.bsky.social!
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!
July 29, 2025 at 7:11 PM
It was such a pleasure to work on this wonderful project with the talented @nitzantal.bsky.social !
Reposted by Dina Hochhauser
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
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
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...
tinyurl.com
July 29, 2025 at 3:48 PM
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
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
Reposted by Dina Hochhauser
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... 🧵
Filamentous cheater phages drive bacterial and phage populations to lower fitness
Many bacteria carry phage genome(s) in their chromosome (i.e., prophage), and this intertwines the fitness of the bacterium and the phage. Most Pseudomonas aeruginosa strains carry filamentous phages ...
www.biorxiv.org
April 3, 2025 at 5:06 PM
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... 🧵
Reposted by Dina Hochhauser
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!
END nucleases: Antiphage defense systems targeting multiple hypermodified phage genomes
Prokaryotes carry clusters of phage defense systems in defense islands that have been extensively exploited bioinformatically and experimentally for discovery of immune functions. However, little effo...
www.biorxiv.org
April 2, 2025 at 4:39 PM
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!
Reposted by Dina Hochhauser
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!
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!
April 3, 2025 at 4:15 PM
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!
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!
Reposted by Dina Hochhauser
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...
A phage-encoded counter-defense inhibits an NAD-degrading anti-phage defense system
Author summary Bacterial viruses (bacteriophages or phages) are widespread and abundant across the planet. Bacteria have a variety of immune systems, often found on mobile genetic elements, to combat ...
dx.plos.org
April 3, 2025 at 4:57 PM
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...
Reposted by Dina Hochhauser
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:
Check it out:
A miniature CRISPR-Cas10 enzyme confers immunity by an inverse signaling pathway
Microbial and viral co-evolution has created immunity mechanisms involving oligonucleotide signaling that share mechanistic features with human anti-viral systems. In these pathways, including CBASS a...
www.biorxiv.org
March 31, 2025 at 4:27 PM
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:
Check it out:
Reposted by Dina Hochhauser
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
🌐https://bfvd.foldseek.com
💾https://bfvd.steineggerlab.workers.dev/
1/3
March 31, 2025 at 5:07 AM
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
🌐https://bfvd.foldseek.com
💾https://bfvd.steineggerlab.workers.dev/
1/3
Reposted by Dina Hochhauser
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.
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
🌐https://bfvd.foldseek.com
💾https://bfvd.steineggerlab.workers.dev/
1/3
March 31, 2025 at 8:57 AM
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.
Reposted by Dina Hochhauser
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
March 31, 2025 at 2:17 AM
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
Reposted by Dina Hochhauser
Structural basis of antiphage defense by an ATPase-associated reverse transcriptase https://www.biorxiv.org/content/10.1101/2025.03.26.645336v1
March 27, 2025 at 3:45 AM
Structural basis of antiphage defense by an ATPase-associated reverse transcriptase https://www.biorxiv.org/content/10.1101/2025.03.26.645336v1
Reposted by Dina Hochhauser
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...
Protein-primed DNA homopolymer synthesis by an antiviral reverse transcriptase
Bacteria defend themselves from viral predation using diverse immune systems, many of which sense and target foreign DNA for degradation. Defense-associated reverse transcriptase (DRT) systems provide...
www.biorxiv.org
March 26, 2025 at 10:13 PM
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...
Reposted by Dina Hochhauser
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.
March 16, 2025 at 9:15 AM
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.
Reposted by Dina Hochhauser
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.
March 11, 2025 at 9:22 AM
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.
Reposted by Dina Hochhauser
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 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
March 3, 2025 at 12:12 PM
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 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
Reposted by Dina Hochhauser
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 🐯
We decided to call them TIGR-Tas systems 🐯
March 1, 2025 at 12:18 AM
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 🐯
We decided to call them TIGR-Tas systems 🐯