Finally taking the time for an #introduction on #mastodon !
I'm a #marine #microbiologist currently leading a #lab at the #EMBL #Heidelberg. My lab is fascinated by the #diversity & #impact of #microbial #interactions across #biological scales, with a particular focus on #eukaryotic #phytoplankton. We think about #symbiosis #epibiosis #viralinfection #singlecell #ecology, often wt #TaraOceans folks⛵
I push for #inclusive #science, and to rethink our #practices in light of #sustainability 🌊
To make it short, much remains to be understood.
What we know of the conservation of immune mechanisms may just be the tip of the iceberg.
Our comparative immunology approach might lead to discover novel defense mechanisms, not only in humans but across eukaryotes🐘🌲🍄🐞 !
Then came the 🔥 question: could we leverage this method to discover novel antiviral factors in humans?
The answer is yes. We identified a family of ISGs, GIMAPs, resembling components of the Eleos system, and showed that they’re active against Herpes and Sindbis virus!
And… we found thousands of hits 🤯.
But are these eukaryotic homologs involved in immunity ?
To tackle this, we focused our analysis on humans, where immunity has been deeply studied and launched a great collaboration with Enzo Poirier.
When we started thinking about this, we hypothesized that:
1) additional antiviral mechanisms might be shared across domains of life
2) novel eukaryotic immune components could be identified by homology with prokaryotic defense systems.
How could we test for that 🤔 ?
We harnessed DefenseFinder, a pipeline that we developed to detect prokaryotic anti-phage systems in bacterial genomes. We decided to run DefenseFinder not on prokaryotic but on eukaryotic genomes !
https://www.nature.com/articles/s41467-022-30269-9
Bacteria and archaea have developed multiple antiviral mechanisms. Here, Tesson et al. present a tool that automatically detects known antiviral systems in prokaryotic genomes, and show that variations in antiviral strategies correlate with genome size, viral threat, and lifestyle traits.
Recent data documented that immune pathways like viperins, cGAS and gasdermins, are shared across domains of life. Bacterial anti-phage systems might thus have been the origin of key immune mechanisms in eukaryotes.
See great perspective https://www.nature.com/articles/s41577-022-00705-4
Prokaryote-eukaryote immune conservations were flagged when novel prokaryotic defense systems were discovered. But, could we do it the other way around? Could we start from the prokaryotic systems and find conservations in eukaryotes?
The cell-autonomous innate immune system has long been considered an evolutionary innovation of metazoans; however, recent evidence challenges this dogma. This Perspective describes the components of antiviral immunity that are conserved from bacteria to humans, and presents potential evolutionary scenarios to explain the observed conservation.
In a new #preprint we report that recently discovered anti-phages systems (Mokosh, Eleos, Lamassu…) have eukaryotic homologs.
We harnessed this conservation to discover novel defense mechanisms in humans.
Our initial census of #antiphage systems in genomes revealed that on average bacteria encode at least 6 anti-phage mechanisms. This paves the way for many interactions between systems.
So we decided to review the existing litterature about #synergy and #regulation of #antiphage systems.
Already cool stuff and clearly a lot more to discover :). Hopefully, this can help to think about how multiple systems coexist in a cell !
https://www.sciencedirect.com/science/article/pii/S1369527422001229
Flora Vincent