Matthaeus Schwarz-Schilling

@mattschwa.bsky.social

postdoc at the weizmann institute (bar-ziv lab) - tinkering with gene expression - bottom-up synthetic biology

We found a new mode by which bacteria deplete NAD+ to protect from phages. And then we found how phages overcome this defense Discovered by talented biochemist Dr Ilya Osterman, read the preprint: tinyurl.com/Narp-ap A thread 🧵

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

tinyurl.com

Excited to share our new paper: we make 30 functional E. coli translation factors in a minimal system (PURE), find threshold concentrations to confirm nascent protein activity and use DNA-brushes to co-localize genes/ribosomes/proteins for simultaneous self-regeneration. doi.org/10.1038/s414...

Autonomous biogenesis of all thirty proteins of the Escherichia coli translation machinery - Nature Communications

The cell-free biogenesis of the protein translation machinery is essential for the creation of a self-regenerating synthetic cell. Here the authors synthesise all 30 E. coli translation proteins in a ...

doi.org

I learned about this dark side of syphilis when I took a history of medicine course. It is a remarkably resistant disease that brought armies to their knees and wrought tremendous societal damage. Ancient DNA Reveals Twisted Roots of Syphilis Go Back 5,500 share.google/V15zBbvnvlbf...

Ancient DNA Reveals Twisted Roots of Syphilis Go Back 5,500 Years

The first known outbreak of syphilis in Europe began at the turn of the 16th century, but on the distant continent of South America, the pathogen's history goes much deeper than that.

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A lot of the recent excitement around methods like AF3 (and followup methods which I often joking call YAAFCs: Yet Another Alpha Fold Clone) is the promise of modeling ligand-bound complexes from only a protein sequence + a small molecule SMILES string (movie from Charm Therapeutics)

A very cool paper from the Frey lab @physicsoflifelmu.bsky.social. Self-assembly governed by compartment geometry... Testing this in (surface-based) artificial cells would be exciting. Delay-facilitated self-assembly in compartmentalized systems | PNAS www.pnas.org/doi/10.1073/...

Delay-facilitated self-assembly in compartmentalized systems | PNAS

Self-assembly processes in biological and synthetic biomolecular systems are often governed by the spatial separation of biochemical processes. Whi...

pnas.org

Excited to release BoltzGen which brings SOTA folding performance to binder design! The best part of this project is collaborating with a broad network of leading wetlabs that test BoltzGen at an unprecedented scale, showing success on many novel targets and pushing the model to its limits!

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Delighted to share my first first author paper, where we realized multi-μm membrane-like shells made entirely of DNA! Huge thanks to co-first author Christoph without whom this wouldn't be possible. This was born from his side-project involving Dipids, stay tuned for the soon-to-be-published paper!

bioRxiv Synthetic Biology@biorxiv-synthbio.bsky.social · 10mo ago

Vesicle-templated self-assembly of freestanding multi-μm DNA shells https://www.biorxiv.org/content/10.1101/2025.10.21.683722v1

A paper in Nature suggests a quarter of heatwave events from 2000-23 would have been near impossible without anthropogenic climate change. The paper also indicates that major carbon emitters are responsible for around 50% of the increase in intensity of these events. ⚒️ 🧪

Systematic attribution of heatwaves to the emissions of carbon majors - Nature

Climate change made 213 historical heatwaves reported over 2000–2023 more likely and more intense, to which each of the 180 carbon majors (fossil fuel and cement producers) substantially contributed.

go.nature.com