Jason Nomburg

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...

Out today: We discovered new viral proteins that target immune signaling molecules, solely based on their AlphaFold-predicted shapes

www.science.org/doi/10.1126/...

Congrats Nitzan Tal and coauthors! Thank you Kranzusch lab for the fun collaboration!

Linking below previous thread on our findings

Prediction of eukaryotic cellular complexity in Asgard archaea using structural modelling - Nature Microbiology A structural catalogue of the Asgard archaeal pangenome reveals hundreds of eukaryotic-like proteins that suggest a higher degree of cellular complexity in the archaeal ancestor of eukaryotes.

🧵 1/10 New paper out in @natmicrobiol.nature.com from my postdoc at @mib-wur.bsky.social! 🎉

How eukaryote-like was the archaeal ancestor of eukaryotes? Sequence searches alone can't tell us — so we used protein structure prediction to look deeper. 🧬
www.nature.com/articles/s41...

1/5
Happy by a recent biorxiv pre-print about DARNA (PD-T7-3) anti-phage defense system. This system is activated by binding to ssDNA, presented by phage SSB, to cleave tRNA in the anti-codon loop.
www.biorxiv.org/content/10.6...

RNA splicing generates a functionally specialized Rep protein isoform in geminiviruses — enabling timely control of the viral cycle. Strikingly, similar strategies might have evolved in DNA viruses infecting different kingdoms: www.biorxiv.org/content/10.6... Spearheaded by @delphinem-p.bsky.social!

Structure and mechanism of antiphage retron Eco2 Nature Structural & Molecular Biology - This study shows how the bacterial retron Eco2 defends against viruses. Phage nucleases trigger activation of Eco2, which cuts RNAs, shuts down protein...

1/6) Hot off the press @natsmb.nature.com 🔥! Jasnauskaite et al. reveal how the minimal bacterial retron Eco2 defends against #phage 🛡️. Phage nucleases trigger Eco2, which cuts RNA, shuts down protein production and stops phage replication 🦠🚫. #phagesky #immunity #microbiology #cryo-em rdcu.be/e4AyH

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...

Inferring context-specific site variation with evotuned protein language models Abstract. Multiple sequence alignments (MSAs) have been traditionally used for making inferences about site-specific diversity in proteins. Recent advancem

Our paper on inferring context dependent entropy using protein language models is officially out in NAR Genomics & Bioinformatics! 🧬🤖

with Adam Strange, Jumpei Ito, and @systemsvirology.bsky.social

academic.oup.com/nargab/artic...

details below...

#NARGAB

Introducing The Structural History of Eukarya (SHE): The first proteome-scale phylogeny constructed entirely from 3D structure.
We computed 300 trillion alignments across 1,542 species to map the tree of life. 🧵👇 (1/5)

The paradox of immune systems conservation between prokaryotes and eukaryotes - Nature Reviews Microbiology The widespread prokaryotic immune systems, in particular restriction–modification, CRISPR–Cas and defensive toxin–antitoxin systems, are absent in eukaryotes, whereas relatively rare ones, such as Arg...

Aude Bernheim @audeber.bsky.social and Eugene Koonin discuss one of most interesting questions in the field connecting bacterial and animal immunity!

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

Bacterial defense via RES-mediated NAD+ depletion is countered by phage phosphatases Many bacterial defense systems restrict phage infection by breaking the molecule NAD+ to its constituents, adenosine diphosphate ribose (ADPR) and nicotinamide (Nam). To counter NAD+ depletion-mediated defense, phages evolved NAD+ reconstitution pathway 1 (NARP1), which uses ADPR and Nam to rebuild NAD+. Here we report a bacterial defense system called aRES, involving RES-domain proteins that degrade NAD+ into Nam and ADPR-1″-phosphate (ADPR-1P). This molecule cannot serve as a substrate for NARP1, so that NAD+ depletion by aRES defends against phages even if they encode NARP1. We further discover that some phages evolved an extended NARP1 pathway capable of overcoming aRES defense. In these phages, the NARP1 operon also includes a specialized phosphatase, which dephosphorylates ADPR-1P to form ADPR, a substrate from which NARP1 then reconstitutes NAD+. Other phages encode inhibitors that directly bind aRES proteins and physically block their active sites. Our study describes new layers in the NAD+-centric arms race between bacteria and phages and highlights the centrality of the NAD+ pool in cellular battles between viruses and their hosts. ### Competing Interest Statement The authors have declared no competing interest. European Research Council, ERC-AdG GA 101018520 Israel Science Foundation, MAPATS grant 2720/22 Deutsche Forschungsgemeinschaft, SPP 2330, grant 464312965 Minerva Foundation with funding from the Federal German Ministry for Education and Research research grant from Magnus Konow in honor of his mother Olga Konow Rappaport Ministry of Aliyah and Immigrant Absorption, https://ror.org/05aycsg86 Clore Scholars Program

Bacterial defense via RES-mediated NAD+ depletion is countered by phage phosphatases | bioRxiv https://www.biorxiv.org/content/10.64898/2026.01.28.702374v1?rss=1

If you're interested in working with me as a graduate student, please mention this in your motivation letter, along with the types of broad research directions you find interesting!

My lab uses protein structure-based bioinformatics and high-throughput, automated experimental validation to study the virus-host conflict throughout the tree of life. You can see more about my lab's interest here: jasonnomburg.com/research/.

I'm recruiting 1-2 grad students through the AITHYRA-CeMM PhD program! Applications are due January 30th. This is a fully-funded PhD program, combining AI and biology to advance biological discovery. Please forward to anyone who may be interested! You can apply here: apply.cemm.at

Diverse bacterial pattern recognition receptors sense the conserved phage proteome Recognition of foreign molecules inside cells is critical for immunity in all domains of life. Proteins of the STAND NTPase superfamily, including eukaryotic nucleotide-binding oligomerization domain ...

A systematic analysis of STAND NTPases and their associated sensor domains in bacterial immunity 🤯 Mind-blowing work !

Such a cool story! Can't wait to read!

Viral enzymes degrade to evade Across all domains of life, immune systems rely on nucleotide-based signaling molecules to activate defense responses. In a recent Cell Host & Microbe study, Doherty, Nomburg, and colleagues identify ...

Viral enzymes degrade to evade

Preview of work identifying & characterizing diverse families of viral two-histidine phosphodiesterase enzymes that degrade nucleotide-based signaling molecules, each with distinct substrate specificities.
www.cell.com/cell-host-mi...

Divergent viral phosphodiesterases for immune signaling evasion Oligonucleotides play fundamental roles in immune system activation across the tree of life. Viral proteins, 2H phosphodiesterases (PDEs), evade immunity by degrading these signals. Doherty and Nombur...

Divergent viral phosphodiesterases for immune signaling evasion

Structure-based searches reveal exceptional diversity among viral 2H phosphodiesterases across the virome that evade immunity by degrading oligonucleotides
www.cell.com/cell-host-mi...

See below for a really exciting opportunity to join AITHYRA through the global adjunct principal investigator program!

Viral enzymes degrade to evade Across all domains of life, immune systems rely on nucleotide-based signaling molecules to activate defense responses. In a recent Cell Host & Microbe study, Doherty, Nomburg, and colleagues identify ...

A very nice Preview of our work in
@cp-cellhostmicrobe.bsky.social
this morning from Chrishan Fernando & Nicole D. Marino! www.cell.com/cell-host-mi...

Big congrats to @petrskopintsev.bsky.social and @isabelesain.bsky.social !

Systematic discovery of TIR-based immune signaling systems in bacteria Toll/interleukin-1 receptor (TIR) domains are important for immune signaling across humans, plants and bacteria. These domains were recently found to produce immune signaling molecules in plant immuni...

I’m happy to share our new preprint! We uncovered the full diversity of bacterial TIR-based antiviral immune signaling, massively expanded the known diversity of Thoeris systems, and revealed conservation of TIR-derived immune signals across the tree of life.

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

📢 We have multiple open PhD positions to study bacterial immune systems using cutting-edge cryo-EM, microbiology, and biochemistry in our group! Join us and uncover how bacterial defenses eliminate predators and engineer next-gen biotech tools.

🔥 Apply by Jan 8, 2026

Details: phd.pages.ista.ac.at

Super cool work by @erinedoherty.bsky.social and @jnoms.bsky.social ! 💪🏼
Viruses hack bacterial immunity by breaking down the nucleotide signals that trigger defence 🦠🧬

So happy to see this work out! Was such a pleasure to co-lead this effort with Erin. Do you like viral immune evasion, and using protein structure to study immune antagonists? Give it a read!

Can't wait to read! Seriously awesome stuff

Congratulations!

Huge congrats to Owen, Jason, and team! Such a fun story

We train machine learning models on millions of proteins. But when it comes to making predictions, do we need them to understand all proteins at once? Often, we need an accurate model for the specific protein we are studying or designing. We address this with ProteinTTT arxiv.org/abs/2411.02109 1/🧵

#AITHYRA, Vienna's new Biomedical AI institute, is hiring Postdocs!

Come work with us. Openings in: 🔹 Generative AI 🔹 Multimodal ML 🔹 Virology 🔹 Enzyme Function

Apply by Nov 20: oeaw.ac.at/aithyra/post... #PostDoc #AI #ML #Vienna #ScienceJobs