Sean Rudd

Macrophages say NO to nucleotide synthesis and salvage instead - Nature Metabolism Metabolic reprogramming is a well-established hallmark of macrophage activation, coordinating bioenergetic and biosynthetic pathways to support immune effector functions. A new study now reveals a pre...

Interesting paper and N&V from @ryanlab.bsky.social

www.nature.com/articles/s42...

www.nature.com/articles/s42...

On-target toxicity limits the efficacy of CDK11 inhibition against cancers with 1p36 deletions https://www.biorxiv.org/content/10.1101/2025.08.03.668359v1

Manipulation of the nucleotide pool in human, bacterial and plant immunity - Nature Reviews Immunology Modification of the nucleotide pool is emerging as key to innate immunity in animals, plants and bacteria. This Review explains how immune pathways conserved from bacteria to humans manipulate the nuc...

We wrote a review on the free nucleotide pool as a central playground in human, bacterial, and plant immunity – now out in Nature Reviews in Immunology

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

Was fun to write this piece with Dina Hochhauser!

Here is a thread to explain the premises

1/

Leveraging autophagy and pyrimidine metabolism to target pancreatic cancer - preLights Two is better than one: Pancreatic ductal adenocarcinoma cells can become resistant to treatment with autophagy inhibitors, but combination with pyrimidine analogues shows promise.

Two is better than one: Pancreatic ductal adenocarcinoma cells can become resistant to treatment with autophagy inhibitors, but combination with pyrimidine analogues shows promise.

New #preLight by Hannah Pletcher covers the #preprint of Suzanne Dufresne and colleagues. Have a look!

Better version of the meme.

Global inhibition of deadenylation stabilizes the transcriptome in mitotic cells In the presence of cell division errors, mammalian cells can pause in mitosis for tens of hours with little to no transcription, while still requiring continued translation for viability. These unique...

New preprint! We solve a mystery you didn't know existed. Mitotic cells lack new transcription but require ongoing translation. Interphase mRNA half life is only 2-4 hrs. So how do cells arrest in mitosis for hours without depleting their transcriptomes?

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

A novel, high-density CRISPR activation platform for mapping cancer dependencies and resistance pathways ex vivo and in vivo https://www.biorxiv.org/content/10.1101/2025.07.22.666069v1

these two threads complement each other spectacularly

1) 👇🏽 use of AI as an attack on expertise and evidence based thinking in resistance to authoritarianism

Deficiency in POLE exonuclease causes synthetic lethality in highly aneuploid cancer cells https://www.biorxiv.org/content/10.1101/2025.07.16.665237v1

Could AI slow science? Confronting the production-progress paradox

Fabulous post by @randomwalker.bsky.social & Sayash raising the same concern many of us have about whether we're on the right track with how we're using AI for science. Everyone should read it, take a deep breath & think through the implications.

www.aisnakeoil.com/p/could-ai-s...

Disorder meets its match Designed protein pockets recognize intrinsically disordered protein regions

Designed protein pockets recognize intrinsically disordered protein regions @science.org
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
www.statnews.com/2025/07/17/n...

From cooperation to conflicts – a complicated relationship between transcription and replication. A tight coordination between transcription and DNA replication is essential to maintain genome stability. Both excessive transcription and upregulated…

Our new review on how the initiation of DNA replication is coordinated with transcription is now online! Congratulations to @syedshahidmusvi.bsky.social!
www.sciencedirect.com/science/arti...

Peer review meltdown in one diagram.

Greater emphasis on glamour journals leads people to try their luck with mediocre papers. This drains the review pool (they often have to be re-reviewed elsewhere). That drops the accuracy of peer review, creating more incentive to submit mediocre papers…

This paper is absolutely bananas and a tour de force of structural bioinformatics. Some random tidbits:

Identification of RNF114 as ADPr-Ub reader through non-hydrolysable ubiquitinated ADP-ribose - Nature Communications Deltex E3s modify ADP-ribosylated targets with ubiquitin, creating a hybrid modification whose readers remains unknown. Here, the authors synthesise a non-hydrolysable probe that mimics the modificati...

A few years back we discovered a dual hybrid protein modification composed of ADP-ribose dinucleotide and ubiquitin (ADPr-Ub). Now we reveal that ADPr-Ub can be further ubiquitinated by the E3 ubiquitin ligase RNF114!
www.nature.com/articles/s41...

www.science.org/doi/10.1126/...

CDK-driven phosphorylation of TRAIP is essential for mitotic replisome disassembly and MiDAS Abstract. Disassembly of the replication machinery (replisome) from chromatin is an active process driven by two ubiquitin ligases Cul2LRR1 and TRAIP, whic

It is finally out 👍😀. Great job of the team (mostly absent from Bsky) and @m-saponaro.bsky.social

CDK-driven phosphorylation of TRAIP is essential for mitotic replisome disassembly and MiDAS url: academic.oup.com/nar/article/...

About our grants As a not-for-profit publisher, The Company of Biologists uses surplus income to benefit biology and the biological community. A key way in which we do this is through our grants, which support and encourage the sharing of knowledge throughout the community by facilitating international collaboration, event attendance and the organisation of scientific meetings, conferences and workshops. We offer the following grants: Scientific Meeting Grants Small Meeting Grants Grants from our Fund for Innovations in Sustainable Conferencing Travelling Fellowships DMM Conference Travel Grants JCS-FocalPlane Training Grants JEB Grants for junior faculty staff Development’s Pathway to Independence programme In addition, the British Society for Developmental Biology, British Society for Cell Biology and the Society for Experimental Biology offer travel grants as part of the funding we give them.

They are a REMARKABLE supporter of scientists and the community. In addition to their five journals, they support dozens of scientific meetings each year, and provide travel grants and other support 2/n
www.biologists.com/grants/

Small molecule OPA1 inhibitors amplify cytochrome c release and reverse cancer cells resistance to Bcl-2 inhibitors OPA1 inhibitors from large-scale screening and chemical optimization restore cancer cell sensitivity to apoptosis-inducing drugs.

Small molecule OPA1 inhibitors amplify cytochrome c release and reverse cancer cells resistance to Bcl-2 inhibitors | Science Advances www.science.org/doi/10.1126/...

Quite a milestone from the Scorrano lab!!!

An unexpected career in cancer metabolism Nature Cancer - Ralph DeBerardinis obtained an MD and PhD from the University of Pennsylvania, then trained in Pediatrics and Medical Genetics at Children’s Hospital of Philadelphia. He moved...

Thanks Nature Cancer for the chance to reflect on some factors that led me to study cancer metabolism. For the trainees and other young scientists: the critical events that shape your career might not be obvious while they are happening. Keep an open mind and trust your instincts.

rdcu.be/evi4I

The Meselson and Stahl experiment demonstrated in 1958 that DNA replicated semi-conservatively.

Meaning, each of the two strands of DNA serves as a template for a new copy to made of the complementary strand.

Foundational finding, elegant experimental design.

High-resolution cryo-EM structures of small protein-ligand complexes near the theoretical size limit https://www.biorxiv.org/content/10.1101/2025.06.30.662489v1

Check out this new review (with animations, natch) of mechanisms of licensing origins of DNA replication - a wonderful (and continuing!) collaboration with Bruce Stillman @cshlnews.bsky.social and John Diffley @crick.ac.uk! www.nature.com/articles/s41...

Congrats to Chris - PhD student in the group - who shared his work on targeting the dNTPase SAMHD1 and was awarded a prize for best talk 💪

I'll be chairing the next meeting in 2027 in Stockholm 🇸🇪. If it sounds like something you'd be interested in, get in touch and I'll keep you posted.

Collage of photos taken during PP25 conference. Includes fireworks, Barcelona scenery, and poster/oral presentations.

And that's a wrap on another Purine and Pyrimidine Society meeting. Held every 2 years - this one in Barcelona - an excellent meeting for those interested in nucleotide metabolism. Lots of discussions between folks at all career stages.

Check out the program here - ppsociety.org/symposium/

#PP25

MetaboList – June 2025 Cystine / Glutathione SLC7A11 is an unconventional H+ transporter in lysosomes Nan Zhou, Jingzhi Chen, Meiqin Hu, Na Wen, Weijie Cai, Ping Li, Liding Zhao, Yaping Meng, Dongdong Zhao, Xiaotong Yang…

Interesting articles on cancer metabolism - and ocassionally, just metabolism- published last month
metabolist.wordpress.com/2025/07/03/m...

Cell enlargement causes mitotic errors and aneuploidy in cells that evade senescence after CDK4/6 inhibition CDK4/6 inhibitors (CDK4/6i) arrest the cell cycle in G1 leading to cellular overgrowth and p53-dependent senescence. They are used to treat metastatic HR+/HER2- breast cancer, but resistance is common...

Delighted to share our latest work showing how cells that evade #senescence after CDK4/6 inhibition are primed to become aneuploid because of their increased size (due to defects in cohesion and the mitotic checkpoint). Great work by fab PhD student Aanchal Pareri 👏🧪

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

Cell enlargement causes mitotic errors and aneuploidy in cells that evade senescence after CDK4/6 inhibition https://www.biorxiv.org/content/10.1101/2025.07.01.662622v1

How chemotherapy shapes hematopoietic stem cells - Nature Genetics Two complementary studies used whole-genome sequencing of single cell-derived hematopoietic colonies to show that chemotherapy results in a marked decrease in hematopoietic stem and progenitor cell (H...

Cancer chemotherapy does a number (as in mutations) to blood cells
2 new reports using single-cell sequencing show the deleterious effects of these drugs, yet another reason for better therapeutic approaches
www.nature.com/articles/s41...
www.nature.com/articles/s41...
www.nature.com/articles/s41...

This is crazy !

A career in science requires a thick skin | EMBO reports EMBO Press is an editorially independent publishing platform for the development of EMBO scientific publications.

Good read. My fav: "If I could distill my scientific life into five words, they would read: “I regret to inform you”"... www.embopress.org/doi/full/10....