Inlay

PhD student @soreklab.bsky.social at Weizmann Institute of Science Evolution of immune systems 🌱🦠

Bohdana Hurieva🇺🇦

🚨After 4 fantastic years in the Sorek lab @soreklab.bsky.social, I’ll be starting my own group at EMBL @embl.org bl.org Hamburg. www.embl.org/groups/oster... Metabolism-driven immunity: phages, metabolites, and discovery of new enzymes, molecules, and pathways 🦠🧬

Folddisco is now published @natbiotech.nature.com. It’s a fast motif search for similar 3D DISCOntinuous residues like catalytic sites or zinc fingers across the entire protein universe. 📄 www.nature.com/articles/s41... 💾 folddisco.foldseek.com 🌐 https://search.foldseek.com/folddisco

Phage receptor-binding proteins are known for their LEGO-like modularity, but we still do not fully understand their evolutionary potential and how it shapes phage host range. Our new preprint examines this systematically in Klebsiella phages. 🔗 www.biorxiv.org/content/10.6... Thread 🧵

Our paper is out in Nature Microbiology: functional analysis of 80 phage sponges, revealing new sponges that inhibit bac immunity by binding the immune signals cCMP, cUMP and N7-cADPR Thanks to all coauthors and our collaborators at the Kranzusch Lab. Congrats Romi! www.nature.com/articles/s41...

Our aRES story is finally out 😀 Beyond what was reported in the preprint, we found that aRES is activated by direct binding of the phage DNA polymerase. Another NAD-degrading defense system — and multiple phage strategies to overcome it. www.sciencedirect.com/science/arti...

Excited to see our work out in @natmicrobiol.nature.com! We uncovered broad functional diversity within phage sponge families🧽. Huge thanks to all coauthors and brilliant collaborators @kranzuschlab.bsky.social @reneechang.bsky.social ! www.nature.com/articles/s41...

(1/6) Thrilled to share this story! In our preprint from my PhD in the @kranzuschlab.bsky.social, with help from the Hatfull lab and @soreklab.bsky.social, we discover RyDEP, a phage-encoded RyR-domain glycosidase that allows phages to evade Thoeris defense. Highlights below! doi.org/10.64898/202...

Preprint Alert 🚨 @philcarella.bsky.social lab stepping into TIR-ritory!! Project started by me but finished by talented PhD student @ebkennedy.bsky.social (Please follow her), with contribution from Zhao He and @jonathandgjones.bsky.social We investigated EDS1-dependency of TIR domain. See thread👇

A nice piece at @science.org covers the exploding field of bacterial immunity, and how it led to the understanding that components of the human immune system evolved from bacterial defenses against phage www.science.org/content/arti...

Predicting phage anti-defenses that shoot the messenger Mahler & @yuping-li.bsky.social highlight @science.org work developing a structure-guided approach to identify phage proteins counteracting bacterial nucleotide signaling defenses using metagenomic data. www.cell.com/cell-host-mi...

Martin Steinegger 🇺🇦

Folddisco enables protein structural motif search in million scale databases.

A better understanding of battles between bacteria and viruses could inspire new medicines

Locked in a constant arms race, bacteria and their phage predators have evolved various defenses and counter-defenses. Compared to the numerous identified defenses, phage-encoded counter-defenses are ...

A functional screen reveals phage sponge proteins that bind Pycsar, Thoeris and CBASS signalling molecules to inhibit bacterial immunity.

Many bacterial defense systems restrict phage infection by breaking down the molecule nicotinamide (Nam) adenine dinucleotide (NAD+) into adenosine di…

www.sciencedirect.com

A functional screen reveals phage sponge proteins that bind Pycsar, Thoeris and CBASS signalling molecules to inhibit bacterial immunity.

Miguel López Rivera

Folddisco finds similar (dis)continuous 3D motifs in large protein structure databases. Its efficient index enables fast uncharacterized active site annotation, protein conformational state analysis and PPI interface comparison. 1/9🧶🧬 📄 www.biorxiv.org/content/10.1... 🌐 search.foldseek.com/folddisco

🧬 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...

@khongsamchia.bsky.social Extremely excited to share the first pre-print from my PhD project in the Carella lab, co-first authored with @khongsamchia.bsky.social 🎉 (Thread below ⬇️) www.biorxiv.org/content/10.6... Huge thanks to all co-authors and the #CarellaCapybaras for all the support 😊

📢 Preprint out! Together with @reneechang.bsky.social @kranzuschlab.bsky.social and the amazing @soreklab.bsky.social, we explored viral sponges to map their diversity and function. Discovered huge diversity, including sponges that inhibit Pycsar & Type IV Thoeris! www.biorxiv.org/content/10.1...

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

Multiple bacterial immune systems, including CBASS, Thoeris, and Pycsar, employ signaling molecules that activate the immune response following phage infection. Phages counteract bacterial immune sign...

A functional screen reveals phage sponge proteins that bind Pycsar, Thoeris and CBASS signalling molecules to inhibit bacterial immunity.

Martin Steinegger 🇺🇦