Francis O'Reilly

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

Ever wondered how Pol II speed is controlled during productive elongation?
Our study reveals that the helicase RECQL5 triggers transcription braking, while the transcription-coupled DNA repair complex restores the elongation rate. #cryoEM #transcription

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

[werner herzog voice] the looney tunes are an abomination. the little bald man shoots the duck in the face but he lives. the coyote is crushed by many anvils, and yet he continues. these unnatural beings cannot die - and without death, what is the value of life itself?

To everyone in a similar scenario: the tactic my doctor's office has taught me is to ask, in writing, for:
1) the name, board specialty, and license number of the doctor making the determination the treatment was not medically necessary;

A multivalent adaptor mechanism drives the nuclear import of proteasomes Nuclear protein homeostasis, including the turnover of transcription factors, critically depends on nuclear proteasomes. After each cell division, proteasomes need to be re-imported into the newly for...

We are very excited to share our recent preprint on the nuclear import mechanism of the proteasome, driven by the multivalent adaptor AKIRIN2! www.biorxiv.org/content/10.1... 🧵 1/6

First paper of our lab today @natureportfolio.bsky.social by Nussi!

We provide a real-time movie on how #transcription and #translation cooperate using #single-molecule FM: we find long-range #ribosome/ RNAP communication mediated by #RNA looping!

@embl.org #RNAbiology #RNASky

t.co/a24Xxcxdo0

Happy Helium
Remembrance Day to all who celebrate! #NMRChat #ChemSky

Publishing the uncut blot