Liam Faller

Protein language models reveal evolutionary constraints on synonymous codon choice Evolution has shaped the genetic code, with subtle pressures leading to preferences for some synonymous codons over others. Codons are translated at different speeds by the ribosome, imposing constrai...

This preprint from Helen Sakharova is one of the coolest things to come out of my lab: “Protein language models reveal evolutionary constraints on synonymous codon choice.” Codon choice is a big puzzle in how information is encoded in genomes, and we have a new angle. www.biorxiv.org/content/10.1...

A molecular switch at the yeast mitoribosomal tunnel exit controls cytochrome b synthesis Abstract. Mitochondrial gene expression needs to be balanced with cytosolic translation to produce oxidative phosphorylation complexes. In yeast, translati

In a new study by our @pelleeas.bsky.social, we reveal how Mrx4 organizes translational regulation of cytochrome b synthesis at the mitoribosomal tunnel exit. Thanks @kawresearch.bsky.social for funding and @stirlingchurchman.bsky.social for the fun collaboration! academic.oup.com/nar/article/...

Here, we show that bacterial ribosomes—often viewed as conserved drug targets—actually vary across species due to extensive sequence variation in their drug-binding residues. In some cases, this divergence may lead to intrinsic drug resistance in certain bacterial clades: doi.org/10.1016/j.ce...

I'm reading the report behind these headlines about glyphosate and it may be the most scientifically illiterate thing I've come across (although it's a close thing with the recent MAHA report). 1/n

The alternative initiation factor eIF2A regulates 40S subunit turnover in ribosome-associated quality control The noncanonical translation initiation factor eIF2A plays critical roles in diverse cellular processes, including the integrated stress response, neurodegeneration and tumorigenesis. However, the pre...

Identified in the 1970s, the precise molecular function of the alternative initiation factor eIF2A has remained unclear. Here, we map its interactome and uncover a surprising role in ribosome-associated quality control (RQC) upon ribosome stalling. 1/x

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

Translational activity of 80S monosomes varies dramatically across different tissues Abstract. Translational regulation at the stage of initiation can impact the number of ribosomes translating each mRNA molecule. However, the translational

Delighted to share paper on translational activity of 80S monosomes across different tissues in 🪰 in @narjournal.bsky.social thanks to fabulous team Albert Blandy Tayah Hopes Elton Vasconcelos @amy-turner96.bsky.social Bulat Fatkhullin Michaela Agapiou Juan Fontana academic.oup.com/nar/article/...

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Detecting ribosome collisions with differential rRNA fragment analysis in ribosome profiling data Abstract. It has become clear in recent years that ribosomes regularly stall during translation. Such translation impairment has many causes, including exp

New paper from the lab! Want to know if there is a difference in ribosome collisions between your samples? We show that you can detect this in the rRNA reads in your ribosome profiling data.

academic.oup.com/nargab/artic...

ZNF574 is a quality control factor for defective ribosome biogenesis intermediates Eukaryotic ribosome assembly is an intricate process that involves four ribosomal RNAs, 80 ribosomal proteins, and over 200 biogenesis factors that pa…

ZNF574 is a quality control factor for defective ribosome biogenesis intermediates

www.sciencedirect.com/science/arti...

m6A alters ribosome dynamics to initiate mRNA degradation m6A is a potent inducer of ribosome stalling and collisions that trigger YTHDF-mediated mRNA degradation, a process that highlights the ribosome as a critical sensor linking translation dynamics to m6...

Very interesting work from Samie Jaffrey's lab: m6A promotes ribosome collisions, with big effects on RNA stability. #RNASky

www.cell.com/cell/fulltex...

Translation dysregulation in cancer as a source for targetable antigens Aberrant peptides presented by major histocompatibility complex (MHC) molecules are targets for tumor eradication, as these peptides can be recognized…

Fantastic stuff by @yardenasamuels.bsky.social lab. The translational regulation of antigen presentation just gets more and more interesting! #RNAbiology #RNASky

www.sciencedirect.com/science/arti...

Ever wondered how several individual RBPs cooperate to repress translation?

Lead by @marcopayr.bsky.social and in great collaboration with @hennig-lab.bsky.social, we simultaneously tracked the binding of several proteins to single mRNA molecules in real-time!

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

Deciphering disordered regions controlling mRNA decay in high-throughput - Nature Using high-throughput functional profiling, how disordered regions control mRNA stability and translation is explored.

Will be taking a deep dive into this today. Congrats to Joe Lobel and Nick Ingolia! #RNAsky #RNAbiology

www.nature.com/articles/s41...

YouTube video by Antoni van Leeuwenhoek FacesofNKI: meet Liam Faller

We’ve loved having @liamfaller.bsky.social at the NKI! As he heads to the UK, we’re sharing this video about this outstanding and likable scientist, whose family inspired his dedication to cancer research.

Best of luck Liam, you will be missed! 💙
www.youtube.com/watch?v=ra88...

Structurally heterogeneous ribosomes cooperate in protein synthesis in bacterial cells - Nature Communications Cells can simultaneously produce structurally dissimilar ribosomes, suggesting functional specialization of distinct ribosome populations. Here, the authors show that distinct ribosomes cooperate rath...

New cryo-EM/ET story - a brilliant collaboration with Sergey Melnikov's lab in Newcastle @sergeymelnikov.bsky.social and Stefan Pfeffer's lab in Heidelberg @pfeffercryolab.bsky.social. Great work in particular by Karla Helena-Bueno and @sophiekopetschke.bsky.social

www.nature.com/articles/s41...

Message to my 11 followers in Bluesky:

We are pleased to announce that registrations for the International EMBO workshop Ribosome Synthesis: from Mechanisms to Therapy 13th Edition are now open!

Details and registration: www.eventsforce.net/hg3/frontend...

The Organizing Committee

Our genome encodes > 7000 microproteins that have been previously ignored in genome annotations. How do these microproteins impact tissue function? Here, we use an in vivo single-cell CRISPR screen to systematically explore microprotein function in the mouse epidermis. 1/9

Great to see this! Congrats Kathrin!

The first paper from the Leppek lab is published today at @embojournal.org!! 🎉
We designed and evaluated a versatile toolbox for determining IRES activity in cells and embryonic tissues.
www.embopress.org/doi/full/10....

Calibrated ribosome profiling assesses the dynamics of ribosomal flux on transcripts - Nature Communications Ribosome profiling faces issues with rRNA contamination and measurements of ribosome numbers on transcripts. Here, the authors develop Ribo-FilterOut and Ribo-Calibration, methods which can be used to...

"these approaches estimate the number of ribosomes on a transcript, the translation initiation rate, and the overall number of translation events before its decay, all in a genome-wide manner" #rnasky #ribosome www.nature.com/articles/s41...

A potent and selective TNKS2 inhibitor for tumor-selective WNT suppression Hyperactive WNT signaling is a potent cancer driver, but clinical translation of WNT inhibitors has been hampered on-target toxicities. WNT signaling can be constrained through inhibition of the PARP ...

New preprint time!!

This one has been brewing in the lab for ~8 years describes a strategy for tumor selective WNT suppression. It was led by an amazing (then) grad student, Jill Zimmerman, with help from a host of lab members and collaborators along the way.

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

A subcellular map of translational machinery composition and regulation at the single-molecule level Millions of ribosomes are packed within mammalian cells, yet we lack tools to visualize them in toto and characterize their subcellular composition. In this study, we present ribosome expansion micros...

Incredible stuff (as always) from the Barna lab:
A subcellular map of translational machinery composition and regulation at the single-molecule level | Science www.science.org/doi/10.1126/...

Philosophical Transactions of the Royal Society B: Biological Sciences: Vol 380, No 1921

Excited to see issue on ribosome heterogeneity and specialisation out @royalsociety.org Philosophical Transactions B. Thanks to authors & co-editors @liamfaller.bsky.social @andershlund.bsky.social Maria Barna. Wonderful cover Bulat Fatkhullin! #ribosomes royalsocietypublishing.org/toc/rstb/202...

High-throughput approaches for the identification of ribosome heterogeneity | Philosophical Transactions of the Royal Society B: Biological Sciences Recent advances in the fields of RNA translation and ribosome biology have demonstrated the heterogeneous nature of ribosomes. This manifests not only across different cellular contexts but also withi...

New review from the lab looking at high throughput methods of identifying ribosome heterogeneity.
Great work from @ferhatalkan.bsky.social, Edwin Kyei-Baffour, and Qi Chang Lin!
royalsocietypublishing.org/doi/10.1098/...

📌 Very cool! Congrats!

On this #InternationalDayofWomenandGirlsinScience we proudly present to you: our roving scientist! She supports women scientists during their maternity leave, which often happens during a crucial phase in their careers.
Read more ➡️ www.nki.nl/news-events/...

The Roving Scientist program was spearheaded by the NKI DEI committee, and we are very grateful to the @nkinl.bsky.social for their support for this and other initiatives. With the on-going assault on such efforts, it is crucial that scientists and their institutions take a stand for what is right.

Science is highly competitive, and contracts are short, so time taken off for parental leave can be very costly for someone's career. We hope to lessen that burden with the Roving Scientist, and to help alleviate the stress from what is already a difficult (but wonderful!) time.

Roving Scientist at NKI_ENGsub This is "Roving Scientist at NKI_ENGsub" by Antoni van Leeuwenhoek on Vimeo, the home for high quality videos and the people who love them.

I am a day late, but to celebrate International Women and Girls in Science Day, @nkinl.bsky.social has launched our Roving Scientist program! This initiative aims to ensure that experiments don't stop when someone takes parental leave.

vimeo.com/1055578665/6...
#WomeninSTEM

🚨Thanks to generous support from @cancerresearchuk.org, we have multiple postdoctoral positions available in our lab (www.mardakhehlab.info) @oxfordbiochemistry.bsky.social to study ribosomes synthesis in cancer. Get in touch if you’re interested + RT and spread the word! 📣 #cancer #RNA 🚨