Luis E. Valentin-Alvarado

Luis E. Valentin-Alvarado

@luisvalentin.bsky.social

HFSP Research Fellow studying microbes, mobile DNA & RNA-guided immune systems.

639 followers383 following48 posts

Luis E. Valentin-Alvarado reposted

Out now in @natcomms.nature.com: We found a plasmid in a preterm infant’s gut microbiome that’s 1.58 million base pairs long, about 30X the size of a typical E. coli plasmid. Then we found its relatives in hundreds of microbiomes worldwide. Read on to learn more about the elusive pMEGAs! 🧵

nature.comIdentification and genetic characterization of megabase-scale plasmids of Enterobacteriaceae - Nature CommunicationsHere, the authors report the identification and characterization of large, up to 1.58 million base-pair-long plasmids in gut microbiomes worldwide, showing that while most genes remain uncharacterized...

Luis E. Valentin-Alvarado reposted

Excited to share this one, led by Theo and my postdoc Bel! We uncover how RNase E generates pAgo guide RNAs and how SPARMA turns that recognition into defense. We solved the cryo-EM structures in the Bravo lab. Great collaboration with Swarts & Zaremba! 🧬 www.researchsquare.com/article/rs-1...

researchsquare.comRNase E-dependent guide generation and activation of the SPARMA defense systemThe evolutionary arms race between prokaryotes and their invaders has driven extensive diversification of defense systems. Prokaryotic Argonautes (pAgos) comprise a diverse family of defense systems i...
Théophile Niault@tniault.bsky.social

New preprint from my Post-Doc in the Swarts lab How are the guide RNAs generated that direct prokaryotic Argonautes to invading DNA? This has been an open question for >10 years. Our new study reveals that the host housekeeping enzyme RNase E is responsible! A 🧵: 1/14

Luis E. Valentin-Alvarado reposted

Very nice discovery from the Jackson, Bravo and Basel labs. Cleaved tRNA ends, loaded with an amino acid, activate a form of bacterial immunity

bioRxiv Microbiology@biorxiv-microbiol.bsky.social

Aminoacylated tRNA tails trigger auxiliary bacterial immunity https://www.biorxiv.org/content/10.64898/2026.10.14.759216v1

Excited to share our work on bacterial immune signaling! Our preprint reveals how RNA-guided Cas13 cleaves host tRNAs to generate small-molecule messengers that activate 2TMβ, linking RNA recognition to membrane damage and phage defense. 1/11

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Our results identify host tRNA as a source of immune messages. We also found other predicted sensor–effector proteins encoded beside Cas13. Their roles remain to be tested, raising questions about how broadly RNA cleavage feeds immune signaling. 10/11

Excited to share our work on bacterial immune signaling! Our preprint reveals how RNA-guided Cas13 cleaves host tRNAs to generate small-molecule messengers that activate 2TMβ, linking RNA recognition to membrane damage and phage defense. 1/11

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We then asked how the candidate messengers affect 2TMβ assembly. Mass photometry showed that synthetic 2′,3′-cUMP and GpU(2′,3′-cp) promoted larger assemblies of the purified, soluble β-barrel. Pocket mutations altered this response. 8/11

In cells, activating the complete system arrested growth, reduced ATP and increased membrane permeability. These effects depended on 2TMβ. Together with the phage assays, the results support a model in which infected-cell shutdown protects the population. 9/11

Excited to share our work on bacterial immune signaling! Our preprint reveals how RNA-guided Cas13 cleaves host tRNAs to generate small-molecule messengers that activate 2TMβ, linking RNA recognition to membrane damage and phage defense. 1/11

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Targeted mass spectrometry directly identified GpU(2′,3′-cp), a two-nucleotide product released by Cas13b6 from tRNA in vitro. This gave us a chemically defined candidate for the signal connecting Cas13 to 2TMβ. 6/11

In cells, removing either the membrane-spanning region or β-barrel of 2TMβ strongly reduced toxicity. The predicted ligand-pocket mutations Y157A and Y197A each also restored viability, linking this pocket to the cellular response. 7/11

Excited to share our work on bacterial immune signaling! Our preprint reveals how RNA-guided Cas13 cleaves host tRNAs to generate small-molecule messengers that activate 2TMβ, linking RNA recognition to membrane damage and phage defense. 1/11

View full thread

We established a phage-free activation assay by targeting GFP RNA in E. coli. Mutating Cas13b6’s extra histidine in HEPEN1 rescued cell viability. Yet the mutant still cleaved tRNAs in vitro, with an altered pattern. This gave us a clue: could specific cuts generate the signal for 2TMβ? 4/11

We then used RNA-seq to map the cuts. Activated Cas13b6 preferentially cleaved a subset of host tRNAs at their anticodon loops. The pattern suggested release of 2′,3′-cUMP and GpU(2′,3′-cp)—candidate signals for its membrane partner, 2TMβ. 5/11

Excited to share our work on bacterial immune signaling! Our preprint reveals how RNA-guided Cas13 cleaves host tRNAs to generate small-molecule messengers that activate 2TMβ, linking RNA recognition to membrane damage and phage defense. 1/11

Many bacterial immune pathways synthesize signals from nucleotides and cofactors. Genome mining revealed Cas13 paired with 2TMβ, a membrane effector usually reported alongside cyclases in CBASS and Panoptes. Could RNA cleavage supply the signal? 2/11

We reconstituted the Cas13–2TMβ system in E. coli and challenged the cells with phages. Both genes were required for full defense. One question remained: what molecule carries the signal from Cas13 to its membrane partner? 3/11

Luis E. Valentin-Alvarado reposted

Luis E. Valentin-Alvarado reposted

My final postdoc project is out today in Nature! We show microbes co-migrated with humans out of Africa; three independent methods agree, and timing matches archaeological / genetic evidence (Fig. 4c). Seeing Fig. 4c for 1st time was one of my most memorable "eureka" moments! doi.org/10.1038/s415...

doi.orgPrehistoric global migration of vanishing gut microbes with humans - NatureMicrobial species disappearing from industrialized populations have evolved with humans over millennia and migrated worldwide with them—this may have consequences for human health.

Luis E. Valentin-Alvarado reposted

None of this year's science Nobel Prizes have gone to women. The number of these prizes to go to women remains at 27 out of more than 600. See how many you can name in our quiz: www.nature.com/immersive/d4...

Luis E. Valentin-Alvarado reposted

Chlorobi paper hattrick! Chlorobi use broad metabolic strategies to support stable blooms www.biorxiv.org/content/10.6... Bloom-forming bacteria heavily invest in anti-phage defense www.biorxiv.org/content/10.6... A 3000-year record of a temperate estuary www.sciencedirect.com/science/arti...

biorxiv.orgAnoxygenic phototrophic Chlorobi use broad metabolic and resource acquisition strategies to support stable near-clonal bloomsAnoxygenic phototrophic green sulfur bacteria (GSB; Chlorobiia) are important primary producers in anoxic and sulfidic environments, whose significance in aquatic ecosystems will expand with coastal deoxygenation. Here, we employed a uniquely comprehensive analytical approach to investigate the formation, maintenance, and collapse of a GSB bloom. We combined multi-omics—V4V5 and synthetic long read 16S rRNA amplicon sequencing, metagenomics, and metaproteomics—with total and GSB-specific cell counts, biogeochemical measurements, and isotopic analysis. The GSB bloom exceeded 109 cells ml-1, among the highest environmental cell densities reported to date, with up to 96 % of the bloom consisting of a single strain-level Prosthecochloris lineage (GSB-TRL01). Extreme sulfide concentrations (> 17 mM) coincided with peaking cell density and a shift in isotopic composition. Bloom persistence is supported by tightly coupled sulfur cycling, high rates of nitrogen fixation, mechanisms to tolerate oxidative stress and maintain redox balance, and nutrient acquisition through outer membrane transport systems. A shift in sulfur oxidizing enzymes towards enzymes with higher sulfide affinity proceeded bloom demise. Prosthecochloris GSB-TRL01 differs from closely related lineages in several outer membrane transport systems, including porins to transport phosphate and tonB-dependent transporters. Collectively, these findings identify physiological and metabolic strategies that may enable near-clonal Prosthecochloris populations to attain extraordinary biomass while coupling the sulfur, carbon, and nitrogen cycles in coastal euxinic environments. ### Competing Interest Statement The authors have declared no competing interest. U.S. National Science Foundation, https://ror.org/021nxhr62, 2205993, 2426305, BIO220128 Simons Foundation, 824763

Luis E. Valentin-Alvarado reposted

BREAKING NEWS The Royal Swedish Academy of Sciences has decided to award the 2026 #NobelPrize in Chemistry to Henri B. Kagan and Kenso Soai “for the discovery of non-linear effects and autocatalysis in asymmetric organic synthesis.”

Luis E. Valentin-Alvarado reposted

Exciting news: @uwgenome.bsky.social will be hiring for two tenure-track faculty positions this year, one open rank and one assistant professor. Both are “Genome Sciences” interpreted broadly so we welcome applicants working in a variety of fields and methods. Ad will be out shortly.

Luis E. Valentin-Alvarado reposted

Huge congratulations to all three Nobel Laureates, and especially Peter Hegemann! 👏 His seminal work on the green alga Chlamydomonas 🦠 laid the foundation for optogenetics. Thank you for putting Chlamy in the spotlight! ✨ Proof that groundbreaking discoveries don't always come from animal models! 🔬

Nobel Prize@nobelprize.org

BREAKING NEWS The 2026 Nobel Prize in Physiology or Medicine has been awarded to Karl Deisseroth, Peter Hegemann and Georg Nagel “for their discoveries concerning light-gated ion channels and optogenetics.”

Luis E. Valentin-Alvarado reposted

Our story with @hobbslabutah.bsky.social discovering CBASS sensing of phage proteases out now in @science.org New data include CBASS recognition of diverse proteases beyond T4, and verifying CD-NTase activation loop cleavage as the trigger for defense in vivo www.science.org/doi/10.1126/...

science.orgPhage proteases activate CBASS antiphage immunityCyclic oligonucleotide–based antiphage signaling systems (CBASS) are bacterial immune pathways evolutionarily related to cGAS-STING (cyclic GMP-AMP synthase–stimulator of interferon genes) in humans. ...
Kranzusch Lab@kranzuschlab.bsky.social

After >10 years of our lab studying bacterial cGAS-like enzymes, @hobbslabutah.bsky.social finally reconstitutes viral sensing in vitro and discovers how these ancient receptors sense phage protease enzymes to detect virion assembly and activate antiviral immunity www.biorxiv.org/content/10.6...

Luis E. Valentin-Alvarado reposted

The shared principles of human and bacterial antiviral immunity An honor to highlight remarkable discoveries from many labs over the past 12 years that unite previously disparate fields of how animal cells and prokaryotes defend against viruses. www.nature.com/articles/s41... rdcu.be/fzwyB

nature.comShared principles of human and bacterial antiviral immunity - NatureThe Review describes shared ancient, conserved mechanisms between human antiviral immunity and bacterial anti-phage systems, outlining universal principles of pathogen sensing, signalling and effector...

Luis E. Valentin-Alvarado reposted

Reminder, registration for the Viral EcoGenomics & Applications (VEGA) 26 symposium is open ! See jgi.doe.gov/work-with-us... for more information

jgi.doe.govVEGA Symposium | Joint Genome InstituteBerkeley, CA
Simon Roux@simrouxvirus.bsky.social

🚨 Registration for VEGA26 is 👏 officially open 👏 🚨 The 5th edition of our Viral EcoGenomics and Applications symposium will be held November 18-19, 2026, on the UC Berkeley campus 🧬 🦠 🔬 🧫 Event website ➡️ jgi.doe.gov/work-with-us... Registration link ➡️ cvent.me/e0RnA0

Luis E. Valentin-Alvarado reposted

my first 'data descriptor'! hoping this one will be useful for folks interested in tracing the distribution of genomes/genes/proteins over physicochemical gradients in the (deep) marine water column.

bioRxiv Microbiology@biorxiv-microbiol.bsky.social

Deeply-sequenced metagenomes and over 1000 draft genomes from the epipelagic to bathypelagic Northeast Pacific Ocean https://www.biorxiv.org/content/10.64898/2026.07.18.739368v1

😍😍😍

Nogales Lab@nogaleslab.bsky.social

Thrilled to share our collab led by Grace Hibshman with the Shipman lab! Type IX retron-Kva2 structure reveals phage detection via an HTH fold, not a primary sequence. We computationally designed triggers that program bacteria cell death, pointing toward designer antimicrobials.

Luis E. Valentin-Alvarado reposted

Humans and bacteria share strategies to defend against viruses. We wondered: could they use each other's genes? Yes, both can! Bacteria can use human immune genes to defend against phages AND Human cells can use bacterial genes for viral defense. www.biorxiv.org/content/10.6...

biorxiv.orgBacterial and human exonucleases mediate interkingdom antiviral immunityAll kingdoms of life have developed strategies to limit viral infection. In humans, interferons induce a suite of antiviral factors that collectively provide immunity. Some human immune genes are homo...

Luis E. Valentin-Alvarado reposted

Our paper "Gene ancestries reveal diverse microbial associations during eukaryogenesis.” is finally out in Nature. Eukaryogenesis was likely a gradual process shaped by multiple microbial partners and virus-mediated gene transfer, rather than a single binary symbiosis. doi.org/10.1038/s415...

Luis E. Valentin-Alvarado reposted

hetro-di-mers are released now.

EMBL-EBI@ebi.embl.org

We told you it wouldn’t be a long wait. 👀 Even more predicted protein structures have been added to the #AlphaFold Database. This time, the database has expanded to include heterodimers – protein complexes made up of two different proteins. alphafold.ebi.ac.uk

Luis E. Valentin-Alvarado reposted

1/ Our new paper in Systematic Biology "Modeling Site-and-Branch-Heterogeneity with GFmix" led by @cgpmcc.bsky.social describes improved ways to model compositional heterogeneity across both sites and branches—an important source of error in deep phylogenomics. doi.org/10.1093/sysb...

doi.orgModeling Site-and-Branch-Heterogeneity with GFmixAbstract. Phylogenetic trees are often inferred from protein sequences sampled from diverse taxa across the tree of life. The compositions of these amino a

Luis E. Valentin-Alvarado reposted

Luis E. Valentin-Alvarado reposted

As an editor at the Biochemical Journal, I'd love to see more papers submitted in the areas of bacterial immune systems / CRISPR / archaeal molecular biology / nucleic acid processing enzymes

Biochemical Society@biochemsoc.bsky.social

Researchers at our Read & Publish institutions can benefit from fee-free OA publishing and access to read content in our journals. Not sure if your institution has signed up? Check out the full list on our website: https://ow.ly/yeH150Z0THn 🧪

Luis E. Valentin-Alvarado reposted

Our lab is proud to present our latest work harnessing Bridge Recombinase for genome-scale editing in diverse bacteria, microbiome editing, and programmable horizontal gene transfer.

bioRxiv Synthetic Biology@biorxiv-synthbio.bsky.social

Bridge recombinase enables versatile rewriting of bacterial genomes https://www.biorxiv.org/content/10.64898/2026.04.29.721476v1