Congratulations @jourdainlab.bsky.social !

Thank you for sharing! We’re lucky to have support from @ihieurope.bsky.social and @horizoneu.bsky.social - it’s the kind of open, collaborative funding that lets discoveries like this happen here in Oxford (and beyond!).

Thank you so much, @rjdlab.bsky.social! Great to see our independent studies complement each other so beautifully and deepen the picture of purine metabolism.

Thank you - much appreciated!

Thanks Jordan!

17/NUDT5 is having a moment – see excellent work from other labs reporting roles for NUDT5 in purine metabolism. These include papers by Kilian Huber and Stefan Kubicek, also out today (see link), and work by Alexis Jourdain and Jun Yang (see next posts)
www.science.org/doi/10.1126/...

JCI study underscores the role of NUDT5 in shaping patient response to thiopurines, pointing to opportunities for more individualised treatment.

www.jci.org/articles/vie...

Link to study from @jourdainlab.bsky.social lab:

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

Shout-out to complementary work from @rjdlab.bsky.social

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

Grateful to Stefan Kubicek & team @cemm.oeaw.ac.at for a fantastic collaboration. Big thanks also to
@ox.ac.uk
@ndm.ox.ac.uk
@cmd.ox.ac.uk
and funders
@horizoneu.bsky.social
@wellcometrust.bsky.social

🌍 Why it matters: This changes how we think about enzyme regulation, metabolism, and cancer-drug response - and shows the power of chemistry to reveal new biology.

🔬 Using proteomics, we discovered NUDT5 binds PPAT, the rate-limiting enzyme in de novo purine synthesis - a “handbrake” mechanism linking metabolism and disease.

🧪 What we did: Tested NUDT5 enzyme inhibitors (no effect) → built a selective NUDT5 degrader (dNUDT5).
Removing the protein revealed an entirely non-enzymatic scaffolding function. #gottaloveTPD

🧩 Motivation: In a CRISPR screen in a “folate trap” model, NUDT5 emerged as a rescue factor in MTHFD1-deficient cells - hinting at a deeper role in cellular metabolism.