Sorek Lab
@soreklab.bsky.social
Congratulations to Sorek lab alumnus Nitzan Tal, who won the prestigious 2025 Science & SciLifeLab prize for the best PhD thesis in Systems Biology! 💫
Read her Prize Assay, published in the journal Science today
www.science.org/doi/10.1126/...
@nitzantal.bsky.social
Read her Prize Assay, published in the journal Science today
www.science.org/doi/10.1126/...
@nitzantal.bsky.social
November 14, 2025 at 6:33 PM
Congratulations to Sorek lab alumnus Nitzan Tal, who won the prestigious 2025 Science & SciLifeLab prize for the best PhD thesis in Systems Biology! 💫
Read her Prize Assay, published in the journal Science today
www.science.org/doi/10.1126/...
@nitzantal.bsky.social
Read her Prize Assay, published in the journal Science today
www.science.org/doi/10.1126/...
@nitzantal.bsky.social
Preprint: Bacteria sense virus-induced genome degradation via methylated mononucleotides
tinyurl.com/ch3damp
We show how molecular byproducts released during virus-induced cell exploitation are used as signals to trigger host immunity
Revealed by the amazing Ilya Osterman. See his thread below👇
tinyurl.com/ch3damp
We show how molecular byproducts released during virus-induced cell exploitation are used as signals to trigger host immunity
Revealed by the amazing Ilya Osterman. See his thread below👇
November 6, 2025 at 10:39 AM
Preprint: Bacteria sense virus-induced genome degradation via methylated mononucleotides
tinyurl.com/ch3damp
We show how molecular byproducts released during virus-induced cell exploitation are used as signals to trigger host immunity
Revealed by the amazing Ilya Osterman. See his thread below👇
tinyurl.com/ch3damp
We show how molecular byproducts released during virus-induced cell exploitation are used as signals to trigger host immunity
Revealed by the amazing Ilya Osterman. See his thread below👇
Together with Melanie Blockesch and David Adams from EPFL, we show that plasmids expressing synthetic anti-defense proteins successfully transform and become retained in V. cholerae, enabling stable plasmid maintenance
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September 2, 2025 at 10:48 AM
Together with Melanie Blockesch and David Adams from EPFL, we show that plasmids expressing synthetic anti-defense proteins successfully transform and become retained in V. cholerae, enabling stable plasmid maintenance
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Engineering phages to express multiple anti-defense peptides in a row enabled them to infect bacteria with multiple defense systems. We believe this approach will allow using phages as therapy against bacteria that encode many defense systems
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September 2, 2025 at 10:48 AM
Engineering phages to express multiple anti-defense peptides in a row enabled them to infect bacteria with multiple defense systems. We believe this approach will allow using phages as therapy against bacteria that encode many defense systems
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We developed a high-throughput screening approach to assess the new designs. The technique rapidly detects peptides that efficiently inhibit bacterial defenses in vivo. We showed in vitro that the peptides tightly bind the defense proteins in nanomolar range affinity, and inhibit their activity
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September 2, 2025 at 10:48 AM
We developed a high-throughput screening approach to assess the new designs. The technique rapidly detects peptides that efficiently inhibit bacterial defenses in vivo. We showed in vitro that the peptides tightly bind the defense proteins in nanomolar range affinity, and inhibit their activity
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New AI tools now allow the design of peptides that bind protein targets. We used RFdiffusion to design peptides that bind active sites of defense system proteins. These peptides do not exist in nature – they are completely “made up”!
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September 2, 2025 at 10:48 AM
New AI tools now allow the design of peptides that bind protein targets. We used RFdiffusion to design peptides that bind active sites of defense system proteins. These peptides do not exist in nature – they are completely “made up”!
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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
Some immune proteins produce altered nucleotides that poison viral replication. Viperin proteins, conserved from bacteria to humans, modify nucleotides to remove their 3’ OH moiety. The modified nucleotide is incorporated into the replicating viral RNA, and terminates viral replication
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July 30, 2025 at 6:05 AM
Some immune proteins produce altered nucleotides that poison viral replication. Viperin proteins, conserved from bacteria to humans, modify nucleotides to remove their 3’ OH moiety. The modified nucleotide is incorporated into the replicating viral RNA, and terminates viral replication
14/16
14/16
As one could expect, viruses developed a huge variety of molecular techniques to evade or suppress host nucleotide signaling. We tried to summarize these in one (rather complex) figure
13/16
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July 30, 2025 at 6:05 AM
As one could expect, viruses developed a huge variety of molecular techniques to evade or suppress host nucleotide signaling. We tried to summarize these in one (rather complex) figure
13/16
13/16
Bacteria, masters of innovation and diversity, employ other immune pathways that use the nucleotide pool for substrates. Type III CRISPR systems build large “rings” of adenosines, while the Pycsar system produces cyclic CMP and cyclic UMP as immune signaling molecules
12/16
12/16
July 30, 2025 at 6:05 AM
Bacteria, masters of innovation and diversity, employ other immune pathways that use the nucleotide pool for substrates. Type III CRISPR systems build large “rings” of adenosines, while the Pycsar system produces cyclic CMP and cyclic UMP as immune signaling molecules
12/16
12/16
Bacterial and plant immune TIRs produce “exotic” immune signaling molecules. In some cases, these are versions of cyclic ADPR (cADPR). In other cases the signaling molecules comprise ADPR conjugated to histidine (His-ADPR) or ADPR conjugated to ATP
11/16
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July 30, 2025 at 6:05 AM
Bacterial and plant immune TIRs produce “exotic” immune signaling molecules. In some cases, these are versions of cyclic ADPR (cADPR). In other cases the signaling molecules comprise ADPR conjugated to histidine (His-ADPR) or ADPR conjugated to ATP
11/16
11/16
Bacteria and plants share immune pathways that rely on ADP-ribose (ADPR) derivatives as immune signaling molecules. These molecules are produced by TIR proteins, which are enzymes that process NAD to generate signaling molecules
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July 30, 2025 at 6:05 AM
Bacteria and plants share immune pathways that rely on ADP-ribose (ADPR) derivatives as immune signaling molecules. These molecules are produced by TIR proteins, which are enzymes that process NAD to generate signaling molecules
10/16
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The cGAS-STING pathway evolved from a large family of bacterial defense systems called CBASS (cyclic oligonucleotide based antiphage signaling systems). These systems produce a variety of cyclic di-nucleotides and tri-nucleotides as signaling molecules. About 15% of all bacteria encode CBASS
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July 30, 2025 at 6:05 AM
The cGAS-STING pathway evolved from a large family of bacterial defense systems called CBASS (cyclic oligonucleotide based antiphage signaling systems). These systems produce a variety of cyclic di-nucleotides and tri-nucleotides as signaling molecules. About 15% of all bacteria encode CBASS
9/16
9/16
The human cGAS-STING pathway uses the nucleotides GMP and AMP as building blocks to generate the immune signaling molecule cyclic GMP-AMP (cGAMP). In other animals, cGAS-like proteins (cGLRs) produce alternative molecules, for example cyclic UMP-AMP
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July 30, 2025 at 6:05 AM
The human cGAS-STING pathway uses the nucleotides GMP and AMP as building blocks to generate the immune signaling molecule cyclic GMP-AMP (cGAMP). In other animals, cGAS-like proteins (cGLRs) produce alternative molecules, for example cyclic UMP-AMP
8/16
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In bacteria, some defense systems convert ATP and deoxy-ATP to their inosine derivatives – ITP and dITP. This halts phage replication in a way that is not yet completely understood
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July 30, 2025 at 6:05 AM
In bacteria, some defense systems convert ATP and deoxy-ATP to their inosine derivatives – ITP and dITP. This halts phage replication in a way that is not yet completely understood
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Many defense mechanisms in bacteria respond to phage by depleting ATP or NAD (nicotinamide adenine dinucleotide). Both nucleotides are essential for energy metabolism. No energy = no viral replication. And sometimes NAD or ATP depletion causes premature activation of phage lysis machinery
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July 30, 2025 at 6:05 AM
Many defense mechanisms in bacteria respond to phage by depleting ATP or NAD (nicotinamide adenine dinucleotide). Both nucleotides are essential for energy metabolism. No energy = no viral replication. And sometimes NAD or ATP depletion causes premature activation of phage lysis machinery
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Nucleotide depletion is a major aspect of antiviral immunity. In humans and bacteria, immune pathways deplete individual deoxy-nucleotides as an antiviral measure. The logic is simple: when the building blocks for making DNA are missing, the virus cannot replicate
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July 30, 2025 at 6:05 AM
Nucleotide depletion is a major aspect of antiviral immunity. In humans and bacteria, immune pathways deplete individual deoxy-nucleotides as an antiviral measure. The logic is simple: when the building blocks for making DNA are missing, the virus cannot replicate
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Preprint: “Structural modeling reveals viral proteins that manipulate host immune signaling”
Using AI-guided structural modeling, we find new families of viral proteins that sequester or cleave host immune signaling molecules
Congrats Nitzan Tal!
www.biorxiv.org/content/10.1...
Using AI-guided structural modeling, we find new families of viral proteins that sequester or cleave host immune signaling molecules
Congrats Nitzan Tal!
www.biorxiv.org/content/10.1...
July 14, 2025 at 7:36 AM
Preprint: “Structural modeling reveals viral proteins that manipulate host immune signaling”
Using AI-guided structural modeling, we find new families of viral proteins that sequester or cleave host immune signaling molecules
Congrats Nitzan Tal!
www.biorxiv.org/content/10.1...
Using AI-guided structural modeling, we find new families of viral proteins that sequester or cleave host immune signaling molecules
Congrats Nitzan Tal!
www.biorxiv.org/content/10.1...
A beautiful discovery by Joel Tan and Philip Kranzusch, out today in Nature:
A DNA-gated molecular guard controls bacterial Hailong anti-phage defence
Congrats Joel and Philip! Was a pleasure to contribute to this discovery together with Sarah Melamed
www.nature.com/articles/s41...
A DNA-gated molecular guard controls bacterial Hailong anti-phage defence
Congrats Joel and Philip! Was a pleasure to contribute to this discovery together with Sarah Melamed
www.nature.com/articles/s41...
April 30, 2025 at 6:59 PM
A beautiful discovery by Joel Tan and Philip Kranzusch, out today in Nature:
A DNA-gated molecular guard controls bacterial Hailong anti-phage defence
Congrats Joel and Philip! Was a pleasure to contribute to this discovery together with Sarah Melamed
www.nature.com/articles/s41...
A DNA-gated molecular guard controls bacterial Hailong anti-phage defence
Congrats Joel and Philip! Was a pleasure to contribute to this discovery together with Sarah Melamed
www.nature.com/articles/s41...
Out in Nature today: A new immune signaling molecule, His-ADPR, is produced by defensive TIR domain proteins in bacteria to protect from phage
Joint work with the Tamulaitienė and Kranzusch labs
www.nature.com/articles/s41...
Congrats Carmel Avraham, Dziugas Sabonis, Renee Chang and co-authors!
Joint work with the Tamulaitienė and Kranzusch labs
www.nature.com/articles/s41...
Congrats Carmel Avraham, Dziugas Sabonis, Renee Chang and co-authors!
April 30, 2025 at 6:44 PM
Out in Nature today: A new immune signaling molecule, His-ADPR, is produced by defensive TIR domain proteins in bacteria to protect from phage
Joint work with the Tamulaitienė and Kranzusch labs
www.nature.com/articles/s41...
Congrats Carmel Avraham, Dziugas Sabonis, Renee Chang and co-authors!
Joint work with the Tamulaitienė and Kranzusch labs
www.nature.com/articles/s41...
Congrats Carmel Avraham, Dziugas Sabonis, Renee Chang and co-authors!
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/...
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/...
January 30, 2025 at 9:57 PM
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/...
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...
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...
January 30, 2025 at 3:40 AM
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...
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...
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
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Acb3 also inhibits the activity of human cGAS, binding residues conserved between the human and bacterial homologs
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January 23, 2025 at 4:12 PM
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
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 of the human protein SARM1
Conservation of TIRs across bacteria, plants and humans leads to conservation of anti-TIR as well
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Conservation of TIRs across bacteria, plants and humans leads to conservation of anti-TIR as well
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January 23, 2025 at 4:12 PM
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 of the human protein SARM1
Conservation of TIRs across bacteria, plants and humans leads to conservation of anti-TIR as well
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Conservation of TIRs across bacteria, plants and humans leads to conservation of anti-TIR as well
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All TIR binders inhibit TIR activity by making direct contacts with the catalytic residue of the TIR active site
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January 23, 2025 at 4:12 PM
All TIR binders inhibit TIR activity by making direct contacts with the catalytic residue of the TIR active site
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