Sign in

Luis E. Valentin-Alvarado

@luisvalentin.bsky.social
632 followers 379 following 47 posts

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

PostsRepliesMedia
Luis E. Valentin-Alvarado @luisvalentin.bsky.social · 09/10/2026
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
110
Luis E. Valentin-Alvarado @luisvalentin.bsky.social · 09/10/2026
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
100
Luis E. Valentin-Alvarado @luisvalentin.bsky.social · 09/10/2026
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
100
Luis E. Valentin-Alvarado @luisvalentin.bsky.social · 09/10/2026
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
110
Luis E. Valentin-Alvarado @luisvalentin.bsky.social · 09/10/2026
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
100
Luis E. Valentin-Alvarado @luisvalentin.bsky.social · 09/10/2026
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
110
Luis E. Valentin-Alvarado @luisvalentin.bsky.social · 09/10/2026
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
100
Luis E. Valentin-Alvarado @luisvalentin.bsky.social · 09/10/2026
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
110
Luis E. Valentin-Alvarado @luisvalentin.bsky.social · 09/10/2026
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
110
Luis E. Valentin-Alvarado @luisvalentin.bsky.social · 09/10/2026
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
26731
Luis E. Valentin-Alvarado @luisvalentin.bsky.social · 11/11/2024
Pre-print 🚨 alert! We used AI protein structure prediction to analyze ~10,000 Borg proteins, revealing potential capsid proteins & viral-like features in these massive elements from methane-eating archaea. Could they be the first archaeal giant viruses? Check it out!
1153
Luis E. Valentin-Alvarado @luisvalentin.bsky.social · 31/01/2024
Nearly 20 years ago, Jill Banfield, Gene Tyson & team transformed #microbiology with their seminal paper on genome-resolved metagenomics. Their innovative approach in reconstructing microbial genomes opened new frontiers in understanding ecosystem dynamics! paper here: www.nature.com/articles/nat...
0146
Luis E. Valentin-Alvarado @luisvalentin.bsky.social · 19/01/2024
GRC-Geobiology was a blast! Kudos to Clara Chan and Karen Lloyd, for putting together a fantastic line-up of experts in deep-time geology, mineralogy, paleontology, and microbiology. Also, it was a pleasure reconnecting with former Banfield lab members and many other great folks.
050