Nitzan Tal
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nitzantal.bsky.social
Nitzan Tal
@nitzantal.bsky.social
Thanks Romish 🤗💕
November 15, 2025 at 2:55 PM
Thank you Aude! ☺️
November 15, 2025 at 5:25 AM
Thanks Rotem! ☺️
November 15, 2025 at 5:25 AM
Thanks Aude!
July 19, 2025 at 5:16 AM
Thank you Brett! 😊
July 14, 2025 at 5:59 PM
Thank you Bohdana!! 😁
July 14, 2025 at 5:43 PM
Thanks Erez! 🥰
July 14, 2025 at 5:43 PM
Thanks Romish! 🤩
July 14, 2025 at 5:42 PM
Thank you Jens! 🤗
July 14, 2025 at 5:42 PM
14/
... the Kranzusch lab, AND the incredible @soreklab.bsky.social that I was so proud to call my home these last few years, it has been a blast!🥰
July 13, 2025 at 7:49 AM
13/
Special thanks to:
@romihadary.bsky.social, Renee Chang, @ostermanilya.bsky.social, Roy Jacobson, @erezyirmiya.bsky.social, Nathalie Bechon,
@dinahoch.bsky.social, Miguel López Rivera, Barak Madhala, Tana Wein, @amitaig.bsky.social, ...👇
July 13, 2025 at 7:49 AM
12/
I was completely in love with this project from day one, and watching it grow was such an incredible experience. 💕

📝 Read more here: tinyurl.com/j4fj9k7f

Huge thanks to everyone who made it happen - especially my brilliant collaborators 👇
Structural modeling reveals viral proteins that manipulate host immune signaling
Immune pathways that use intracellular nucleotide signaling are common in animals, plants and bacteria. Viruses can inhibit nucleotide immune signaling by producing proteins that sequester or cleave t...
tinyurl.com
July 13, 2025 at 7:49 AM
11/

This study shows how structure can illuminate function in bacteria–phage warfare.🦠👩‍🔬🧪

And how structural convergence opens a powerful path to decode the function of mysterious ORFs in viral genomes! 🔦
July 13, 2025 at 7:49 AM
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Family 3:

This one surprised us!
We initially thought Acb5 was a sponge, but we quickly realized it was different: it doesn’t bind the signal, it cleaves it! ✂️

This enzyme cuts cGAMP into cAMP and cGMP, depleting CBASS signaling.
A new class of viral immune evasion enzyme
July 13, 2025 at 7:49 AM
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Family 2:

Lockin proteins form cog-like hexamers with deep, positively charged grooves.

We solved their structure at 1.6 Å bound to 3′cADPR, revealing not just a powerful anti-Thoeris sponge, but also an incredible structure.
It looks like a beautiful molecular flower. 🌸
July 13, 2025 at 7:49 AM
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Sequestins dimerize to form binding pockets for 3′cADPR.

They’re widespread across phages, including in phage T4, where the long-uncharacterized protein Y16Q turns out to be a functional anti-Thoeris Sequestin.
July 13, 2025 at 7:49 AM
7/
Family 1:

We first found Sequestin through a fusion-based approach: it often appeared fused to known sponges like Tad2 & Acb4 (huge shoutout to
@romihadary.bsky.social
for spotting this!)
It checked all the boxes: small, oligomeric, positively charged.
It blocks Thoeris by binding cADPR!
July 13, 2025 at 7:49 AM
6/

To test candidates from different families across multiple immune systems, we built a 96-well transformation and phage-infection workflow (otherwise – far too many transformations!).

This let us screen >120 proteins systematically for anti-defense activity.
July 13, 2025 at 7:49 AM
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We screened ~32 million viral proteins using AlphaFold-Multimer, pocket prediction, & electrostatics filters to find candidates that look like anti-defense proteins!

We tested >120 against multiple defense systems and looked for anti-defense phenotypes.
July 13, 2025 at 7:49 AM
4/

We noticed that known anti-defense sponges of signaling molecules, despite having no sequence similarity, share key structural traits:

🔹 Small size
🔹 Homo-oligomeric assembly
🔹 Positively charged pockets at protomer interfaces

We used these features to guide our search.
July 13, 2025 at 7:49 AM
3/
Viral sponges are especially elegant.
Instead of destroying immune signals, they soak them up - binding molecules like cGAMP or 3′cADPR and keeping the alarm from ever sounding, giving the phage a chance to win.

🖼️ Beautiful figure from Mayo-Muñoz et al.
July 13, 2025 at 7:49 AM
2/
Bacteria use immune systems like CBASS, Thoeris & Pycsar, which produce nucleotide messengers (cGAMP, 3′cADPR, cCMP etc.) to signal phage infection and activate immune effectors.

But phages fight back! Using proteins that bind or cleave these signals to shut down the response
July 13, 2025 at 7:49 AM