Francis O'Reilly

inpreparation.substack.com/p/i-wrote-em...

We are running the cryo-ET image processing workshop again this year! Come learn everything tomo: STA, segmentation, heterogeneity analysis from @baradlab.com @williamnwan.bsky.social and others!

Apply!

The ribosome synchronizes folding and assembly to promote oligomeric protein biogenesis Large oligomeric proteins constitute a major fraction of proteomes, but are difficult to refold in vitro, raising the question of how cells direct their biogenesis. Roeselová and Shivakumaraswamy et a...

Our latest cotranslational folding story is now published @cp-molcell.bsky.social. Really cool (I think) new ideas about how exactly the ribosome directs folding and assembly to make sure complicated proteins mature efficiently in cells.
www.cell.com/molecular-ce...

When RNA Degradation 🤝 meets 🤝 Protein Degradation! tinyurl.com/E3TDMD In a collaboration of @bartellab.bsky.social and Schulman lab, we show that, in target-directed microRNA degradation (TDMD), 2-RNA-factors recruit an E3 ligase and induce the degradation of not only a protein but also RNA (1/5).

ER-associated single-capped vaults are surprising and really cool!🤩 Some even contain ribosomes. Vault function is still mysterious but a role in protein quality control seems plausible.

Also great to see Dicty in the #TeamTomo spotlight! #ProtistsOnSky @kgeissler.bsky.social @becklab.bsky.social 🧪

How does messenger RNA (mRNA) get out of the nucleus to become a protein? Eukaryotic mRNA is packaged, exported, and then translated in the cytoplasm. But how do these steps work? And what are open questions? Check out our new review for our take: www.annualreviews.org/content/jour... (1/3)

This work is now officially published
@natsmb.nature.com
with some fun new analyses included in the revised version. Congratulations to all the authors! @connyyu.bsky.social @rappsilber.bsky.social @lrsinn.bsky.social @fjoreilly.bsky.social www.nature.com/articles/s41...

DirectContacts2: A network of direct physical protein interactions derived from high-throughput mass spectrometry experiments Cellular function is driven by the activity proteins in stable complexes. Protein complex assembly depends on the direct physical association of component proteins. Advances in macromolecular structur...

We are excited to share our preprint describing DirectContacts2! Here we develop a machine learning model to discriminate between direct and indirect protein interactions. We use our model to construct a highly accurate wiring diagram of the human cell.

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

This in situ strategy opens the door to mapping dynamic macromolecular machines directly in their cellular context, and hints that much has been missed by previous AP-MS studies of the interactome.

Using PhIX-MS combined with cryo-EM and integrative modeling, we discovered how the ubiquitination enzyme UBE3C, the reductase TXNL1, and the assembly factor PSMD5 bind to the proteasome, providing important information on their functions.

Many proteasome binders are transient or low-affinity and are very difficult to visualize with conventional methods. To overcome this, we developed PhIX-MS (Photo-induced In situ Crosslinking Mass Spectrometry) to map native protein interactions directly inside cells.

Structures of dynamic interactors at native proteasomes by PhIX-MS and cryoelectron microscopy Proteasome function depends on a network of transient interactions that remain structurally and functionally unresolved. We developed PhIX-MS (Photo-induced In situ Crosslinking-Mass Spectrometry), a ...

‼️ Exciting new preprint from a close collaboration with Kylie Walters' group. Our study maps the binding sites of key regulators of the proteasome in situ.
www.biorxiv.org/content/10.1...

New preprint: In situ Architecture of #Plasmodesmata.

Using #cryoET, #AlphaFold & proteomics, we uncover the native organization of plant intercellular nanopores.

🔗 doi.org/10.1101/2025...

🧪🧵1/n
#teamtomo #PlantScience #Physcomitrium #Arabidopsis #cryoEM

A great lineup of speakers!

Time to get signed up for the next Symposium on Structural Proteomics! This time in beautiful Milan 6th-8th October.
ssp2025.squarespace.com

Human gut bacteria bioaccumulate per- and polyfluoroalkyl substances - Nature Microbiology Human gut bacteria bioaccumulate per- and polyfluoroalkyl substances (PFAS), commonly known as forever chemicals, in intracellular aggregates. Colonization of gnotobiotic mice with bioaccumulating bac...

Beautiful work from my friend @kiranrpatil.bsky.social . Gut bacteria can accumulate Forever chemicals and help us get rid of them! Happy we could contribute! www.nature.com/articles/s41...

Postdoctoral Scientist - Structural Studies - Dr Sjors Scheres - LMB 2640 - Cambridgeshire job with MRC Laboratory of Molecular Biology (LMB) | 12840844 Postdoctoral Scientist Starting Salary: £41,344 Fixed term: 3 years MRC Laboratory of Molecular Biology, Cambridge, UK We are looking for a postdoc...

We have a 3-year funded postdoc position to work on structures of #amyloid filaments. If you are an expert in protein biochemistry, structural biology or #cryoEM / #cryoET, this could be for you! Feel free to email me with any questions. Come join us! 🤩

www.nature.com/naturecareer...

Biblically accurate nitrogen

ERC grantee wins the Shaw Prize in Life Science and Medicine 2025 Shaw Prize honours ERC-funded research in molecular imaging

🎉 Congratulations to Wolfgang Baumeister @maxplanck.de, awarded the 2025 #ShawPrize in Life Science & Medicine for pioneering work in cryo-ET!

Learn more 👉 europa.eu/!JBXDBG
#FrontierResearch #ERCSyG #CryoET #StructuralBiology #shawprize2025

We've updated our AFESM website to now include biome filtering, allowing exploration of protein structures adapted to specific environments.
🌐 afesm.foldseek.com
Read more about the work in the skeetorial
🦋 bsky.app/profile/mart...
or our preprint
📄 www.biorxiv.org/content/10.1...

We are looking for a postdoctoral fellow to join us to explore telomerase regulation by histones. Please get in touch if this may interest you.

I’m excited to share my first paper in the Farnung lab, in which we report four cryo-EM structures of the human DNA replication machinery engaging with and progressing into a nucleosome.

Image of a world map showing the journey of Cuckoo Tom when he hitched a ride on a cruise ship. Arrows show the ships journey from West Africa to the Atlantic Ocean, across to the coast of South America, past Puerto Rico, the United States, up to Iceland and to the UK. A headshot of Cuckoo Tom features, alongside the wording: Tagged, Norfolk 2023. Current location: UK. Mode of transport: cruise ship. Outline of a cruise ship in white sits over the ocean. BTO logo features top right of the image.

One of our satellite-tagged Cuckoos has hitched a ride on a cruise ship and is now in the UK, the earliest one of our superstar Cuckoos has ever reached us! 😮🛥️🧵

A broad-spectrum lasso peptide antibiotic targeting the bacterial ribosome Nature - A new lasso peptide antibiotic exhibits broad-spectrum activity against Gram-negative and Gram-positive bacteria by interfering with bacterial protein synthesis, is unaffected by common...

The latest discovery from the lab and great colleagues at McMaster and U Illinois, Chicago. Lariocidin, a new lasso peptide antibiotic that inhibits the ribosome. rdcu.be/efdha

In a new Science study, cryo–electron tomography captures the in-cell architecture of the mitochondrial respiratory chain, illuminating how the coordinated action of molecular machines drives life’s fundamental energy conversion.

Learn more in this week's issue: scim.ag/3FA3Ygq

Grandpa Simpson bluthing himself

“You see, that was funny because no one could imagine one banana costing $10.”

Happy retirement to Francis Collins, a scientific and administrative hero. He was always a strong advocate for the importance of biological research and the results are obvious and impressive.

Out of the lab, into the wild: when @pauligroup.bsky.social's Andi Pauli puts on her @ox.ac.uk blue, you know it's business time! Austria's national broadcast ORF interviewed her on how #Vienna has become such an amazing place for life science research.

Foldseek-Multimer—now published in @naturemethods.bsky.social—our fast multimer search tool, enables complex comparisons against the full PDB in seconds. It comes with BFMD, a collection of 300K+ predictions gathered from community projects.
📄 nature.com/articles/s41...
🌐 search.foldseek.com