Kranzusch Lab

Cell death is a fundamental mechanism of antiviral immunity across diverse organisms, including bacteria. As my final PhD project with @jbdsf.bsky.social, I was curious whether cell death is required for successful immunity with the ancient cGAS pathway known as ‘CBASS.’

Spoiler – the answer is no!

Elegant study from @erinhuiting.bsky.social @jbdsf.bsky.social on CBASS phage inhibition without loss of cell viability. Especially interesting to see this phenotype with a CapV membrane-targeting effector and evidence for 3'3'-cGAMP transport!

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

CBASS limits bacteriophage production while maintaining cell viability in Pseudomonas aeruginosa https://www.biorxiv.org/content/10.64898/2026.02.24.707611v1

A 5-hydroxymethylcytosine DNA glycosylase provides defense against T-even bacteriophages https://www.biorxiv.org/content/10.64898/2026.02.25.707755v1

SNIPE is a widespread bacterial defence system that exploits the spatial organization of phage genome injection to specifically target viral DNA, distinguishing self from non-self in prokaryotic immune systems @nature.com @mitpress.bsky.social
www.nature.com/articles/s41...

Tomorrow at the #SystemsVirologyJournalClub, Joel Tan (@joelmjtan.bsky.social) will present his work with Philip Kranzusch (@kranzuschlab.bsky.social) on a DNA-gated molecular guard that control bacterial anti-phage defence.

Paper: pubmed.ncbi.nlm.nih.gov/40306316/

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...

Diversity and distribution of bacterial DNA polymerases Abstract. DNA polymerases are key players in DNA replication, repair, and maintenance. However, the overall abundance, diversity, and distribution of bacte

Check out largest scale analysis of bacterial DNA polymerases! Diversity and distribution of bacterial DNA polymerases url: academic.oup.com/nar/article/...

Next one in a storm of preprints from our lab's amazing scientists.. Recent-ex-postdoc, #newPI @cathyhernandez.bsky.social studied thermal ecology of marine bacteria isolated near New Haven. Turns out, response of this bacterium to temperatures is shaped by prophages!

#phagesky #microsky

Amy Lee, PhD, and Max Fels, PhD, of Dana-Farber Cancer Institute

New research by @danafarbernews.bsky.social’s Amy Lee, PhD, and @mfels.bsky.social in @cp-cell.bsky.social reveals that giant DNA viruses encode a distinct & functional IF4F translation-initiation complex to drive protein synthesis, blurring the line between living cells and viruses. bit.ly/4rS3Uew

Sonomi Yamaguchi of Dana-Farber Cancer Institute

New research featured in @nature.com from Sonomi Yamaguchi of @danafarbernews.bsky.social’s @kranzuschlab.bsky.social discovers “p3diT” as a nucleotide immune signal in bacteria and suggests similar signals may function as negative regulators in human immunity.

Read more: bit.ly/3MTjLL6

Congratulations to Ben Morehouse @benmorehouse.bsky.social and the other 2026 Michelson Prize Awardees. All five newly funded projects are incredibly exciting areas of immunology!

www.michelsonmedicalresearch.org/news/michels...

Free readcube link to her paper: rdcu.be/e4A7X

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...

News piece in Science @science.org about Max's research:

"Giant viruses hijack their hosts’ protein factories"

www.science.org/content/arti...

Max Fels @mfels.bsky.social from our lab discovers giant DNA viruses that infect amoeba encode eIF4E and the entire suite of 4F complex proteins to control mRNA translation, including beautiful crystal structures of viral 4E bound to modified mRNA 5' caps:

www.cell.com/cell/fulltex...

Lokiarchaeon CBASS ❤️

Screen of 300 chromatin regulator proteins from the Nuñez lab at UC-Berkeley @jamesknunez.bsky.social www.nunezlab.org enables universal programmable transcriptional engineering in nearly any eukaryotic cell!

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

Abstract submission is now OPEN for the 2026 Symposium on the Immune System of Bacteria!

sisb2026.rockefeller.edu
🗓 May 5–7, 2026
📍 Rockefeller University, New York City
⏰ Abstract deadline: March 16, 2026

Attendance will be capped, be sure to register early and secure your spot.

See you in NYC!

🧪🧬New preprint We present cryo-EM structures of reconstituted CTCF–nucleosome complexes, showing CTCF dimerization drives nucleosome oligomerization into defined higher-order assemblies. Disrupting CTCF–CTCF interfaces in mESCs reduces looping and impairs differentiation. tinyurl.com/CTCF-nucleos...

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...

Amazing findings in geometry-based immune activation! Two bacterial defence systems detect phage-encoded ring oligomers, assemble high-order molecular complexes, and trigger abortive infection.

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

Structural genomics sheds light on protein functions and remote homologs across the insect tree of life - Cell Research Cell Research - Structural genomics sheds light on protein functions and remote homologs across the insect tree of life

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

Chemical inhibition of a bacterial immune system Bacteriophages are promising alternatives to antibiotics for treating bacterial infections. However, bacteria possess immune systems that neutralize bacteriophages. Zang et al. discover small molecule...

Chemical inhibition of a bacterial immune system

Small molecules inhibit type II Thoeris anti-phage systems from diverse bacteria. One compound, IP6C, improves phage-therapy against P. aeruginosa & is effective against Thoeris in polymicrobial communities
www.cell.com/cell-host-mi...

Hallmarks of cancer—Then and now, and beyond Hanahan revisits the evolving framework of cancer hallmarks, synthesizing 25 years of conceptual refinement into a multidimensional view of tumor biology. This review highlights how aberrant capabilit...

Today at Cell: A new #HallmarksofCancer review by Doug Hanahan: www.cell.com/cell/fulltex...
This review marks 25 years since the original seminal Cell review by Hanahan & Robert Weinberg and its impactful follow up in 2011.
@cp-cell.bsky.social @cellpress.bsky.social

GlycoRNA complexed with heparan sulfate regulates VEGF-A signalling - Nature Heparan sulfate proteoglycans facilitate the assembly of clusters of glycoRNAs and cell surface RNA-binding proteins, which negatively modulate VEGF-A signalling and angiogenesis.

New #glycotime discovery from @raflynn5.bsky.social’s lab @bostonchildrens.bsky.social @harvard.edu, cell surface glycoRNA-RBP complexes organized by heparan sulfate PG nanoclusters that modulate VEGF signaling

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

🧬 Metabolic arms race continues!
We discovered a new NAD⁺-depleting bacterial immune system aRES and phage enzymes that overcome it.
Our preprint is out: www.biorxiv.org/content/10.6...

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

Pre-assembly of biomolecular condensate seeds drives RSV replication Nature - Viral ribonucleoprotein–viral protein networks form pre-replication centres that nucleate viral factories and drive respiratory syncytial virus replication.

Now out in Nature! We visualize infection of the RNA virus RSV in real-time with single-vRNP resolution to understand how RSV establishes viral factories, biomolecular condensates that act as sites of viral replication. A huge collaborative effort led by Dhanushika Ratnayake!

rdcu.be/e1bBW

Great new story from Sophie Helaine and Molly Sargen!

www.helainelab.com