Phage receptor prediction from genome sequencing alone. Bacterial receptor (blue) interacting with phage proteins (purple) is shown here

📣Huge preprint 🔔
Today we share something our group has been working toward for a long time, led by @lucasmoriniere.bsky.social We asked can we predict which receptor a phage targets from its genome sequence alone? For most phages, we couldn’t. So Lucas set out to do something I had only dreamed of.

AlphaFold as a prior: experimental structure determination conditioned on a pretrained neural network Nature Methods - ROCKET improves experimental structure elucidation by integrating implicit structural knowledge from OpenFold, a trainable reimplementation of AlphaFold2, with X-ray...

ROCKET 🚀 inference-time optimization of AlphaFold to fit structural data is published! rdcu.be/fa9YH
Since our preprint, we’ve pushed it to regimes where other methods break: low resolution, weak signal, real experimental edge cases. Here’s what we learned: 1/15

The PhageExpressionAtlas just made it to bioRxiv. Visually explore the transcriptomes of phage-host interactions or harness the database for analysis across infections! Please leave feedback, which functionalities/data you find missing.
Preprint:
www.biorxiv.org/content/10.6...

#phagesky #microsky

We recently came across this study (published on @elife.bsky.social ) and it caught our eye, so we decided to make a brief #phagesky comment on it
📝Premise
✅What we liked
❓Questions it raised for us
elifesciences.org/reviewed-pre...

All images are taken from the paper

Thanks a lot for the supportive words!

Thank you! Much appreciated :)

And very grateful to the people at @chimerax.ucsf.edu as we used their software to prepare the movie 👏🏻👏🏻

Thanks for sharing! Summary of the manuscript in the thread: bsky.app/profile/arit...

This research was performed at the University of Copenhagen, at the NNF-CPR and CFIM. More details about the fibre dynamics and the tape measure protein in the manuscript. Keep an eye for more movies in the future 📽️🍿 www.biorxiv.org/content/10.6... #phagesky

New preprint of our friend Aritz Roa @aritz-roa.bsky.social with Nicholas Taylor @nmitaylorlab.bsky.social - even if phage mechanics are not your thing, check out their MAGNIFICENT video of T4 host recognition + infection directly im the post! 🎬🧬🔥

Many years of work that continue thanks to the people in Taylor group (special mention to Leyre Marin-Arraiza, @vkleinsousa.bsky.social, Mònica Santiveri, Nicole R. Rutbeek, Haidai Hu, and Nicholas M. I. Taylor) and our collaborators, particularly @aharms485.bsky.social and @damienpiel.bsky.social.

Summary figure on phage T4 infection, showing the contraction and the conduit formation.

Together, these results provide a structural framework for how contractile phages regulate genome delivery and superinfection exclusion. They also allow us to visualize how genome translocation into the host occurs:

It was already known that a superinfection exclusion protein (Imm) can block phage genome translocation at the inner membrane. We co-expressed Imm and TMP and purified their complex, supporting the idea that TMP interacts with the inner membrane to form the translocation conduit.

Since we knew which TMP domains were involved in conduit formation, we thought we might as well try to study it with cryoEM… right? Not the easiest protein, but we managed to purify a dimer showing the predicted helical bundle domain and the transmembrane helix of TMP.

The distal end tube of phage T4 during genome release. From the pre-contracted state (panel a) to the post-contracted state where the genome ejection is arrested (panel b) and finally the open conduit for genome release (panel c)

After tail contraction, the genome remains in the virion. This is mediated by TMP binding to the distal end of the tube, preventing premature DNA release! This is ejected upon membrane interaction when the TMP-tube complex rearranges to create a conduit for genome translocation into the host.

This allowed us to investigate the retracted state of the long tail fibres and how they extend to bind to the host. We could also define their rotation and how this may be transmitted to the peripheral baseplate of the virion.

Phage T4 states and genome release. CryoEM maps and structural models to show the virions.

We characterised three phage T4 states: the pre-contracted virion with retracted LTFs, the post-contracted virion before genome ejection, and the post-ejected genome state of the post-contracted virion upon lipid membrane interaction.

We build on decades of work on this model phage and hope to expand the understanding of how myoviruses regulate the early infection process, from fibre extension to genome translocation, including a superinfection exclusion mechanism that binds the TMP.

🚨Preprint! Happy to share the research from my PhD “Genome delivery of a contractile tailed phage and its superinfection exclusion mechanism”. We use cryoEM to study the genome ejection of the phage T4, revealing how the tape measure protein regulates the process.
www.biorxiv.org/content/10.6...

Mapping bacteriophages SBGrid member Mihnea Bostina helps to uncover the first high-resolution, head-to-tail structural map of a Felixounavirus bacteriophage.

Mapping bacteriophages: a publication highlight from @keandreyam.bsky.social featuring a new article from the lab of Mihnea Bostina at the @universityofotago.bsky.social & colleagues.

Read more here: buff.ly/Wgfu3bt

#SBGrid #cryoem

Everyone interested in #virus loves a #bacteriophage right? It's amazing they are the most abundant and diverse biological entity on the planet, yet were discovered just over 100 years ago! To give them the attention we believe they deserve, npj Viruses has launched three collections on #phages:

Systematic mapping of bacteriophage gene essentiality with HIDEN‑SEQ The constant arms race of bacteriophages and their bacterial hosts has inspired major breakthroughs in biotechnology and shaped phages as fierce predators with great clinical potential to fight multid...

#microsky #phagesky

(Fancy!) transposon-insertion sequencing identifies essential genes in #phage. By @aharms485.bsky.social & Co.

www.biorxiv.org/content/10.1...

Congrats to @jimbeanbio.bsky.social for this very cool paper!

Cryo-EM structure of bacteriophage Bas63 reveals structural conservation and diversity in the Felixounavirus genus Cryo-EM of phage Bas63 reveals unique capsid and tail features, offering insights into Felixounavirus evolution and architecture.

Cryo-EM structure of bacteriophage Bas63 reveals structural conservation and diversity in the Felixounavirus genus | Science Advances www.science.org/doi/10.1126/...

Great manuscript and lovely thread to read, congrats!

Structural characterization of an extracellular contractile injection system from Photorhabdus luminescens in extended and contracted states - Nature Communications Marín-Arraiza and colleagues report the cryo-EM structures of an extracellular contractile injection system from Photorhabdus luminescens in extended and contracted states, providing structural insigh...

Thrilled to see Leyre’s PhD work finally out!

We reported the #cryoEM structures of an extracellular contractile injection system from P. luminescens in extended and contracted states, providing structural insight into its architecture and contraction mechanism 🔬
www.nature.com/articles/s41...

Awesome #phage #bioinformatics preprint from @shelbyeandersen.bsky.social, who is also very close to finishing her PhD and on the lookout for her next position 👀

Muyuan Chen has turned structural biology into an immersive experience with his new video game Meowtabolism, now available on Steam.
Try the demo here: store.steampowered.com/app/4045010/...
Give Muyuan feedback: steamcommunity.com/app/4045010
#ScienceGaming #StructuralBiology #CryoEM #STEMOutreach

Many of the most complex and useful functions in biology emerge at the scale of whole genomes.

Today, we share our preprint “Generative design of novel bacteriophages with genome language models”, where we validate the first, functional AI-generated genomes 🧵

SPEAR (bacterial nanosynringe) enables loading of different types of cargo (including folded ribonucleoproteins and single-stranded DNA) and targeting of defined cell types both in vitro and in vivo
www.nature.com/articles/s41...
@natbiotech.nature.com @zhangf.bsky.social