Hugo Vaysset
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hugovaysset.bsky.social
Hugo Vaysset
@hugovaysset.bsky.social
PhD student in bioinformatics/genomics @mdmlab.bsky.social, Institut Pasteur, Paris.
Reposted by Hugo Vaysset
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...
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...
www.biorxiv.org
December 4, 2025 at 9:25 AM
Reposted by Hugo Vaysset
Very happy to share our collaborative project on FAM118 proteins - noncanonical sirtuins that form filaments and process NAD in human and other vertebrate cells.
Filament formation and NAD processing by noncanonical human FAM118 sirtuins
Nature Structural & Molecular Biology - Baretić and Missoury et al. identify vertebrate proteins FAM118B and FAM118A as sirtuins similar to bacterial antiphage enzymes and show that...
rdcu.be
November 17, 2025 at 11:37 AM
Reposted by Hugo Vaysset
1/9 Metagenomics lets us read microbiomes in nature without cultivation, but writing (editing) them in their native context is still a major challenge.

Meet MetaEdit: a platform for pathway-scale metagenomic editing inside the gut microbiome. science.org/doi/10.1126/...
Metagenomic editing of commensal bacteria in vivo using CRISPR-associated transposases
Although metagenomic sequencing has revealed a rich microbial biodiversity in the mammalian gut, methods to genetically alter specific species in the microbiome are highly limited. Here, we introduce ...
science.org
November 14, 2025 at 2:25 PM
Reposted by Hugo Vaysset
📖Latest from the lab:
Evo. characterization #antiviral #SAMD9/9L across #kingdoms🚶‍♀️🦍🦠🧫🖥️: ancient #convergence + #adaptations @natecoevo.nature.com

Led by amazing Alexandre Legrand +major contributions by Rémi Demeure & Amandine Chantharath @ciri-lyon.bsky.social 1/n

www.nature.com/articles/s41...
Evolutionary characterization of antiviral SAMD9/9L across kingdoms supports ancient convergence and lineage-specific adaptations - Nature Ecology & Evolution
A search for analogues of the human SAMD9/9L antiviral genes identifies convergent evolution of this gene family in the bacterial and animal kingdoms, with species-specific and recent genomic signatur...
www.nature.com
November 12, 2025 at 5:55 PM
Reposted by Hugo Vaysset
Reposted by Hugo Vaysset
Bacteria can sense when a virus starts shredding their genome — by detecting methylated mononucleotides.
Here’s the story of how we discovered the Metis defense system 👇
www.biorxiv.org/content/10.1...
November 6, 2025 at 5:00 AM
Reposted by Hugo Vaysset
Our new preprint is out 🥳🥳🥳

Henipaviruses, like Nipah and Hendra, package their genomes inside helical shells built by thousands of nucleoproteins. These nucleocapsids are essential to protect the viral RNA, but how do they ever let the polymerase in to read the sequence?

👇
November 3, 2025 at 12:26 PM
Reposted by Hugo Vaysset
Excited to share: DNA glycosylases are diverse antiviral effectors. They recognize phage base modifications and initiate genome destruction. A structure‑guided approach made the scope of this discovery possible! 🧪 #phagesky doi.org/10.1101/2025... #phage #microbiology
Antiviral Defence is a Conserved Function of Diverse DNA Glycosylases
Bacteria are frequently attacked by viruses, known as phages, and rely on diverse defence systems like restriction endonucleases and CRISPR-Cas to survive. While phages can evade these defences by cov...
doi.org
October 30, 2025 at 12:16 PM
Reposted by Hugo Vaysset
@prczhaoyansong.bsky.social’s deep dive into the dark matter of compost communities is now out 🎉 Genomic islands hijack jumbo phages—whose capsids enable transfer of large tracts of DNA—shedding new light on the scale & scope of phage-mediated gene flow 😎

www.pnas.org/doi/10.1073/...
Jumbo phage–mediated transduction of genomic islands | PNAS
Bacteria acquire new genes by horizontal gene transfer, typically mediated by mobile genetic elements (MGEs). While plasmids, bacteriophages, and c...
www.pnas.org
October 28, 2025 at 6:36 PM
Reposted by Hugo Vaysset
OpenFold3-preview (OF3p) is out: a sneak peek of our AF3-based structure prediction model. Our aim for OF3 is full AF3-parity for every modality. We now believe we have a clear path towards this goal and are releasing OF3p to enable building in the OF3 ecosystem. More👇
October 28, 2025 at 6:30 PM
Reposted by Hugo Vaysset
Lab’s first paper is out!! We show the first structures of #Asgard #chromatin by #cryo-EM 🧬❄️
Asgard histones form closed and open hypernucleosomes. Closed are conserved across #Archaea, while open resemble eukaryotic H3–H4 octasomes and are Asgard-specific. More here: www.cell.com/molecular-ce...
October 28, 2025 at 3:07 PM
Reposted by Hugo Vaysset
Many antiphage systems use NAD+, in many ways.
@hugovaysset.bsky.social reviewed them all!

Read to know more about all their molecular mechanisms, how phages counteract them, their distribution in bacteria and their conservation in eukaryotic immunity!
www.cell.com/molecular-ce...
The multifaceted roles of NAD+ in bacterial immunity
In this review, Vaysset and Bernheim examine how nicotinamide adenine dinucleotide (NAD+) is a key player in diverse and widespread bacterial antiphage defense systems and phage counterdefense. The au...
www.cell.com
October 17, 2025 at 5:55 PM
Reposted by Hugo Vaysset
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
Reposted by Hugo Vaysset
Today in @nature.com , we highlight how a cousin of CRISPR-Cas10, mCpol, establishes an evolutionary trap in anti-phage immune systems.

Check out @erinedoherty.bsky.social and my work from @doudna-lab.bsky.social lab here:
www.nature.com/articles/s41...
A miniature CRISPR–Cas10 enzyme confers immunity by inhibitory signalling - Nature
Panoptes, an anti-phage defence system against virus-mediated immune suppression, is revealed.
www.nature.com
October 1, 2025 at 5:57 PM
Reposted by Hugo Vaysset
Our story describing the Panoptes bacterial immune defense system is now finally peer-reviewed and published today! www.nature.com/articles/s41...
The Panoptes system uses decoy cyclic nucleotides to defend against phage - Nature
The Panoptes antiphage system defends bacteria by detecting phage-encoded counter-defences that sequester cyclic nucleotide signals, triggering membrane disruption and highlighting a broader strategy of sensing immune evasion through second-messenger surveillance.
www.nature.com
October 1, 2025 at 4:05 PM
Reposted by Hugo Vaysset
🧬🌉Online @science.org Megabase-scale human #genome rearrangement with programmable bridge recombinases | Science www.science.org/doi/10.1126/...
Megabase-scale human genome rearrangement with programmable bridge recombinases
Bridge recombinases are naturally occurring RNA-guided DNA recombinases that we previously demonstrated can programmably insert, excise, and invert DNA in vitro and in Escherichia coli. In this study,...
www.science.org
September 29, 2025 at 10:01 PM
Reposted by Hugo Vaysset
YprA family helicases provide the missing link between diverse prokaryotic immune systems https://www.biorxiv.org/content/10.1101/2025.09.15.676423v1
September 16, 2025 at 6:17 AM
Reposted by Hugo Vaysset
A new theme issue of #PhilTransB examines the evolutionary history of bacterial immune systems, their modes of action, and the patterns how different bacterial immune systems are distributed across different ecosystems. Read: buff.ly/Z4qdxY1
September 5, 2025 at 4:01 PM
Reposted by Hugo Vaysset
How do bacteria choose what type of defences to use against phages? We explored that question in the last paper I worked on as a postdoc at the Uni of Exeter @uniofexeteresi.bsky.social with Stineke van Houte, Stefano Pagliara and Edze Westra (not on Bluesky)
doi.org/10.1098/rstb...
Phage provoke growth delays and SOS response induction despite CRISPR-Cas protection | Philosophical Transactions of the Royal Society B: Biological Sciences
Bacteria evolve resistance against their phage foes with a wide range of resistance strategies whose costs and benefits depend on the level of protection they confer and on the costs for maintainance....
doi.org
September 4, 2025 at 4:02 PM
Reposted by Hugo Vaysset
📢 New preprint alert!
We designed synthetic proteins that can block bacterial immune systems, allowing phages + plasmids to overcome natural defenses.
This could transform phage therapy + genetic engineering.
Here’s what we found 🧵
Preprint🔗: www.biorxiv.org/content/10.1...
Synthetically designed anti-defense proteins overcome barriers to bacterial transformation and phage infection
Bacterial defense systems present considerable barriers to both phage infection and plasmid transformation. These systems target mobile genetic elements, limiting the efficacy of bacteriophage-based t...
www.biorxiv.org
September 2, 2025 at 7:36 AM
Reposted by Hugo Vaysset
👏 Huge congrats to @audeber.bsky.social, group leader and head of our Molecular Diversity of Microbes lab, on being named a 2025 Vallee Scholar! Her pioneering work on ancestral immunity opens new perspectives for biomedical innovation. 🔬🌍

@valleefoundation.bsky.social

#Science #Immunity
September 2, 2025 at 9:44 AM
Reposted by Hugo Vaysset
Preprint: De-novo design of proteins that inhibit bacterial defenses

Our approach allows silencing defense systems of choice. We show how this approach enables programming of “untransformable” bacteria, and how it can enhance phage therapy applications

Congrats Jeremy Garb!
tinyurl.com/Syttt
🧵
Synthetically designed anti-defense proteins overcome barriers to bacterial transformation and phage infection
Bacterial defense systems present considerable barriers to both phage infection and plasmid transformation. These systems target mobile genetic elements, limiting the efficacy of bacteriophage-based t...
www.biorxiv.org
September 2, 2025 at 10:48 AM
Reposted by Hugo Vaysset
Congratulations Rotem Sorek @soreklab.bsky.social on receiving the Gruber prize today in Stockholm
August 23, 2025 at 9:24 AM
Reposted by Hugo Vaysset
#News&Views

Bacterial prions form amyloids in response to phage infection and induce cell death to prevent viral replication, similar to the processes in fungi and across the tree of life.

#MicroSky

www.nature.com/articles/s41...
Amyloids in bacterial antiphage defence - Nature Microbiology
Bacterial prions form amyloids in response to phage infection and induce cell death to prevent viral replication, similar to the processes in fungi and across the tree of life.
www.nature.com
August 21, 2025 at 5:47 PM
Reposted by Hugo Vaysset
Stoked to finally have a preprint out for Phold, our tool that uses protein structural information to enhance phage genome annotation #phagesky 1/n

www.biorxiv.org/content/10.1...
Protein Structure Informed Bacteriophage Genome Annotation with Phold
Bacteriophage (phage) genome annotation is essential for understanding their functional potential and suitability for use as therapeutic agents. Here we introduce Phold, an annotation framework utilis...
www.biorxiv.org
August 8, 2025 at 7:11 AM