Aude Bernheim

A human homolog of SIR2 antiphage proteins mediates immunity via the Toll-like receptor pathway Key actors of mammalian immunity originated from bacterial antiphage systems. The full extent of immune system conservation between bacteria and eukaryotes is unknown. Here, we show that the silent in...

#NatMicroPicks

Ancient Proteins, Modern Immune Insights! 🦠

A conserved protein family member activates inflammation via the Toll-like receptor pathway in mammals highlighting new aspects of human immunity.

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

Manipulation of the nucleotide pool in human, bacterial and plant immunity - Nature Reviews Immunology Modification of the nucleotide pool is emerging as key to innate immunity in animals, plants and bacteria. This Review explains how immune pathways conserved from bacteria to humans manipulate the nuc...

We wrote a review on the free nucleotide pool as a central playground in human, bacterial, and plant immunity – now out in Nature Reviews in Immunology

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

Was fun to write this piece with Dina Hochhauser!

Here is a thread to explain the premises

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Expression level of anti-phage defence systems controls a trade-off between protection range and autoimmunity - Nature Microbiology The authors examine several defense systems and find that increased expression enhances their protection range, albeit at a cost of autoimmunity.

Expression level of anti-phage defence systems controls a trade-off between protection range and autoimmunity
By Nitzan Aframian and Avigdor Eldar.
www.nature.com/articles/s41...

Kiwa is a membrane-embedded defense supercomplex activated at phage attachment sites Zhang, Todeschini, and Wu et al. show that the bacterial defense system Kiwa senses phage attachment at the membrane and assembles a transmembrane complex that halts infection by blocking phage DNA re...

Thrilled to see our Kiwa story out today! A membrane-associated supercomplex that senses infection and blocks replication and transcription.

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

Huge congratulations to Yi and Zhiying for bringing it home, to Thomas for starting us off, and to all the collaborators.

Very proud to have our lab’s first work published in @cp-cellhostmicrobe.bsky.social!

In this work, we use functional metagenomics to find phage defenses from human and soil microbiomes!

Congrats to first author @luis840alberto.bsky.social !

www.cell.com/cell-host-mi...

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Recurrent acquisition of nuclease-protease pairs in antiviral immunity Antiviral immune systems diversify by integrating new genes into existing pathways, creating new mechanisms of viral resistance. We identified genes encoding a predicted nuclease paired with a trypsin...

Excited to finally share this work!
We noticed a pair of genes - a nuclease and a protease - shuffles between antiviral systems. We show how proteolysis activates the nuclease, triggering defense in known and unknown immune contexts.
tinyurl.com/2uwwy4ty

Manipulation of the nucleotide pool in human, bacterial and plant immunity - Nature Reviews Immunology Modification of the nucleotide pool is emerging as key to innate immunity in animals, plants and bacteria. This Review explains how immune pathways conserved from bacteria to humans manipulate the nuc...

NEW Review from @soreklab.bsky.social @dinahoch.bsky.social explains how immune pathways manipulate the availability of nucleotides, chemically modify nucleotides to generate immune signalling molecules, and produce altered nucleotides that poison viral replication
#immunosky #microsky #phagesky

A human homolog of SIR2 antiphage proteins mediates immunity via the Toll-like receptor pathway Key actors of mammalian immunity originated from bacterial antiphage systems. The full extent of immune system conservation between bacteria and eukaryotes is unknown. Here, we show that the silent in...

Evolutionary molecular biology paying dividends again - this time in finding new modulators of innate immunity - www.science.org/doi/10.1126/...

👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀

Another amazing discovery from the @audeber.bsky.social lab, working with @enzopoirier.bsky.social to demonstrate functional conservation of immune mechanisms across domains of life!
Congrats to @hugovaysset.bsky.social and co-authors!!

Thanks Rotem!!

Wow - an important component of a central human innate immune pathway was discovered based on homology to a bacterial anti-phage defense system

A beautiful example showing how new knowledge on bacterial immunity translates to discoveries important for human health

A human protein inherited from bacteria reveals an overlooked aspect of human immunity What if the study of bacteria could illuminate our understanding of human immunity? In recent years, scientists have been exploring unexpected links between human proteins involved in the body’s defen...

🧬 From bacteria to humans: a new study led by @institutcurie.bsky.social, @institutpasteur.bsky.social & @inserm.fr reveals SIRal, a novel human immune protein with ancestral roots. A new path for immunotherapy?

🔗 Read: www.pasteur.fr/en/press-are...

Protein-centric view of immunity IDs SIRims, a new family of immune proteins conserved across kingdoms of life w/ SIRal driving TLR-driven inflammation and antipathogen defense @science.org @enzopoirier.bsky.social @audeber.bsky.social @hugovaysset.bsky.social
www.science.org/doi/10.1126/...

This is cracking research.
And the video is great.

We are all evolved from hot pondlife.
www.youtube.com/watch?v=rqWj...

Fascinating story ⬇️

Crowd favourite @audeber.bsky.social You heard it first @ Lorne Proteins 50th anniversary - the incredible story of bacterial antiphage protein homologs in human, mice, fish... with conserved innate immune function is out now in Science. 🤩🤯 🙌
bsky.app/profile/aude...

Thanks!

Thanks!

1/16 New pre-print from the Sternberg Lab!
We uncover how temperate phages can use RNA-guided transcription factors to remodel the flagellar composition of their bacterial host and enhance their fitness.
Find the preprint and full story here: tinyurl.com/mshwjd77

simply wonderful science 🤩

A human homolog of SIR2 antiphage proteins mediates immunity via the Toll-like receptor pathway Key actors of mammalian immunity originated from bacterial antiphage systems. The full extent of immune system conservation between bacteria and eukaryotes is unknown. Here, we show that the silent in...

Many components of human immunity evolved from ancient pathways in bacteria. A beautiful story from @audeber.bsky.social‬ @enzopoirier.bsky.social‬ leverages this evolutionary connection to discover SIRal as a signaling protein in animal TLR-mediated innate immunity.

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

YouTube video by MDM Lab Ancestral immunity: when bacteria shed light on our defenses

Congratulations to lead authors D. Bonhomme and @hugovaysset.bsky.social for such an interdisciplinary work, and to @benmorehouse.bsky.social for the 🤩 biochemistry.

We are recruiting on this topic, so get in touch!

To finish a small video for a non scientific audience
youtu.be/rqWjTSqE2U8

This work shows the power of a protein-centric view of immunity.

By following conserved immune domains, we can uncover hidden biology, predict immune genes across eukaryotes, including non-model organisms, and humans.

The discovery of SIRal also opens new therapeutic avenues.

The immune modules conserved across the tree of life: Towards a definition of ancestral immunity A subset of prokaryotic antiviral systems are conserved in eukaryotes and have crucial roles in immune pathways. This Essay introduces the concept of ancestral immunity, which refers to the set of imm...

This discovery shows that immunity is not just a human thing... but an ancient, shared story — from bacteria to us.

We name this ancestral immunity, that is, immune modules which span kingdoms of life, conserved across billions of years. More on this 👇
journals.plos.org/plosbiology/...

Overall we discovered a novel family of immune genes conserved across bacteria and eukaryotes.

SIRal, a human homolog, is a novel actor of the TLR pathway.

Much remains to be understood about SIRal and Sirims in immunity, but 🦠 will help us along the way.

How does this family of proteins function?

Like their bacterial relatives, eukaryotic SIRims — including human SIRal — use NAD+ in vitro. This enzymatic activity (NADase) seems ancient and conserved across the tree of life.

Given SIRal’s role in mammalian innate immunity, we wondered if SIRal’s immune function could be conserved in other eukaryotes.

Turns out that SIRim proteins are detected in ~20% of eukaryotic genomes.

We focused on the zebrafish version — and showed it contributes to immunity in vivo 🐟🦠