Jack Bravo

@jpkbravo.bsky.social

Assistant Professor @ ISTA Using cryo-EM to understand how bacteria defend themselves https://bravo-lab.org/

Honored to be named a 2026 Vallee Scholar! 🎉 Excited about the research ahead and especially to be part of the Vallee Scholar community.

Institute of Science and Technology Austria (ISTA)@istaresearch.bsky.social · last wk.

Congratulations to ISTA’s @jpkbravo.bsky.social​, named a 2026 Vallee Scholar! 🎉 The award supports innovative, curiosity-driven biomedical research. Bravo’s lab studies bacterial immune systems and how they distinguish self from non-self. Read more: https://shorturl.at/FyLbw

A family of lanthipeptides with anti-phage function Discovery of 2,000+ lanthipeptide biosynthetic gene clusters with anti-phage potential. Lanthivirins inhibit phage replication by targeting phage proteins & interfering with phage DNA replication. www.cell.com/cell-host-mi...

A family of lanthipeptides with anti-phage function

Shomar, Guillaume, et al. report the genomics-driven discovery of a family of more than 2,000 lanthipeptide biosynthetic gene clusters with anti-phage potential. They experimentally demonstrate anti-p...

cell.com

Gabija restricts phage circularization & DNA replication Gabija prevents phage genome circularization & replication w/out impacting bacterial host. Exposed DNA ends & phage end-binding proteins license DNA targeting while RecBCD protects host from Gabija www.cell.com/cell-host-mi...

Gabija restricts phage circularization and DNA replication

Gabija acts early during phage infection, preventing phage genome circularization and replication. Phage DNA end-binding proteins prevent RecBCD loading onto linear DNA, and the absence of RecBCD lice...

cell.com

Mechanism of tandem-repeat DNA synthesis by an antiviral reverse transcriptase | bioRxiv

Mechanism of tandem-repeat DNA synthesis by an antiviral reverse transcriptase

Defense-associated reverse transcriptases (DRTs) employ DNA synthesis to protect bacteria against phage infection. We previously showed that DRT10, a tripartite system comprising an RT, a noncoding RNA (ncRNA), and a SLATT effector protein, catalyzes protein-primed, tandem-repeat DNA synthesis in a mechanism strikingly analogous to eukaryotic telomerase. However, the structural basis by which the RT-ncRNA complex directs repeat addition processivity and controls repeat length remains unknown. Here we present cryo-EM reconstructions of two evolutionarily diverse DRT10 RT-ncRNA systems that reveal an unanticipated 2:1 architecture, wherein two RT monomers bind opposite sides of a single, pseudo-symmetric ncRNA. Biochemical experiments demonstrate that each RT monomer reverse transcribes the template encoded on its respective side of the ncRNA, but only one generates the long repetitive product, with the template sequence defined by the distance between two flanking stem-loop anchors. Together with earlier studies of DRT2, DRT3, and DRT9, our findings identify a conserved mechanistic logic underlying ncRNA-templated tandem-repeat synthesis across Class 2 UG antiviral systems, despite vastly different architectural solutions. ### Competing Interest Statement Columbia University has filed a patent application related to this work. S.H.S. is a co-founder and scientific advisor to Dahlia Biosciences, a scientific advisor to CrisprBits and Prime Medicine, and an equity holder in Dahlia Biosciences and CrisprBits. The remaining authors declare no competing interests.

biorxiv.org

Excited to share our discovery of a new programmable RNA-guided DNA-targeting system hiding inside bacteriophages that predates CRISPR. We call it VIPR (Viral Interference Programmable Repeat), and it uses an entirely new logic to find its targets. Thread + link below.

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Phage-encoded CasPRs transcriptionally silence diverse CRISPR-Cas systems | bioRxiv https://www.biorxiv.org/content/10.64898/2026.02.23.707548v1?rss=1

Phage-encoded CasPRs transcriptionally silence diverse CRISPR-Cas systems

Anti-CRISPRs (Acrs) are diverse proteins or RNAs that protect invading phages and plasmids from host CRISPR-Cas immunity. Most Acrs neutralize their cognate Cas proteins via direct physical interaction. Here we describe CasPRs, a particularly widespread family of DNA-binding Acrs that recognize specific sequence motifs within cas gene coding regions, thereby blocking RNA polymerase and silencing transcription. We demonstrate that eight diverse CasPRs bind to the cas8b gene to repress the type I-B CRISPR-Cas system in its native host, Listeria seeligeri . Meanwhile, a CasPR from Streptococcus dysgalactiae silences type II-A CRISPR-Cas immunity by binding to the cas9 coding sequence. We found that one CasPR is required to inhibit CRISPR immunity during lysogeny by its host prophage. Taken together, our results indicate that members of the CasPR family have diverged to silence completely unrelated CRISPR types, and suggest transcriptional repression is a common mode of phage-mediated immune antagonism. ### Competing Interest Statement AJM is a co-founder and advisor of Profluent Bio. The other author declares no competing interests. National Institute of General Medical Sciences, https://ror.org/04q48ey07, R35GM142460, GM136534 U.S. National Science Foundation, FAIN2235762 Defense Advanced Research Projects Agency, https://ror.org/02caytj08, HR00112590142 Rita Allen Foundation, https://ror.org/0515k5w36

biorxiv.org