Alexis A. Jourdain

Vitamins: a tool to exploit against cancer A research group at Unil has identified a new mechanism that exposes the vulnerability of tumor cells when they are deprived of vitamin B7.

🥜🦀 A research group @jourdainlab.bsky.social @dib-unil.bsky.social @fbm-unil.bsky.social @unil.bsky.social has identified a new mechanism that exposes the vulnerability of #tumor #cells when they are deprived of #vitamin B7, also known as #biotin.

Press release here 👉 www.unil.ch/news/en/1770...

Functional nutrient-genetic profiling reveals biotin and FBXW7 are essential to bypass glutamine addiction Lisci et al. present a unified model revealing how cells escape glutamine addiction, a metabolic vulnerability of several cancers. Combining systematic genetic and nutrient screens, they show that bio...

Our story on #FBXW7 and #biotin in #glutamine_addiction is now peer-reviewed and published in Molecular Cell! Heroic work led by the very first postdoc of the lab @miriamlisci.bsky.social. Have a look!

www.cell.com/molecular-ce...

Happy to share that the our manuscript "Cyclin CLB2 mRNA localization and protein synthesis link cell cycle progression to bud growth" is now finally out in its final form @natcomms.nature.com
www.nature.com/articles/s41...
Below a short🧵 with the key findings!

10 days left to apply! 👇

One month left to apply to the open postdoc position in our lab! 👇

Alexis Jourdain nommé EMBO Young Investigator Professeur assistant à la FBM, Alexis Jourdain a été sélectionné pour l’EMBO Young Investigator Programme. Cette distinction offre au spécialiste du métabolisme un soutien important pour consolider le...

👏 Bravo à Alexis Jourdain qui rejoindra l’EMBO Young Investigator Programme @embo.org au 1er janvier 2026. L’initiative européenne soutient des scientifiques en début de carrière dirigeant leur propre équipe de recherche.
🔗 www.unil.ch/news/fr/1764...

@jourdainlab.bsky.social @dib-unil.bsky.social

Thrilled and incredibly honored to be selected as an @embo.org Young Investigator! Still can’t quite believe it 🎉 Huge thanks to EMBO and to all the amazing mentors, colleagues, and collaborators who made this possible!

@fbm-unil.bsky.social
@unil.bsky.social
@snsf.ch

Uridine-sensitized screening identifies demethoxy-coenzyme Q and NUDT5 as regulators of nucleotide synthesis - Nature Metabolism A uridine-sensitized CRISPR-Cas9 screening identifies demethoxy-CoQ as an alternative electron acceptor in the absence of CoQ, and NUDT5 as a regulator of de novo pyrimidine synthesis via its interact...

Rich collections of papers on #mitochondrialdisease from the last 2 weeks! 📚
biomed.news/bims-mitdis/...
biomed.news/bims-mitdis/...

@biomednews.bsky.social @mitoscientist.bsky.social
@gavinmcstay.bsky.social

Demethoxy-CoQ and NUDT5 in nucleotide synthesis
www.nature.com/articles/s42...

An inherited mitochondrial DNA mutation remodels inflammatory cytokine responses in macrophages and in vivo in mice - Nature Communications Inherited mitochondrial DNA mutations can result in diverse clinical phenotypes. Here, the authors characterise a heteroplasmic tRNAAla mutation (m.5019A>G) in mice and demonstrate that macrophages...

Very excited to announce that the first paper from the lab is now live @natcomms.nature.com #mitochondria #immunometabolism

This work was led by postdoc Eloise marques with many important contributions from all of our co-authors.

Please check it out!

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

We are hiring a postdoc! 🧪
▶️ Project: nucleotide metabolism (genomics & biochemistry)
▶️ Start date: spring 2026 (flexible)
▶️ More info and application: tinyurl.com/3kjrbb2x
Please share 🌏

@fbm-unil.bsky.social @dib-unil.bsky.social @unil.bsky.social @snsf.ch

Good Sunday!. A wonderful selection of papers in #cancermetabolism and #mitochondrialbiology is waiting for you here: biomed.news/bims-camemi/... @biomednews.bsky.social #keepreading

"99.9 per cent of everything you think, and of everything you do, is for yourself—and there isn't one."
-Wei Wu Wei

Thank you :)

Ce gène qui sauve les chimiothérapies Des scientifiques du Département d’immunobiologie de l’Unil mettent en évidence un nouveau mécanisme susceptible de faire dérailler certains traitements du cancer.

🔦 Flash #Recherche

🧬🦀 Des scientifiques @dib-unil.bsky.social @unil.bsky.social identifient un nouveau #mécanisme susceptible de faire dérailler certains #traitements du #cancer. En jeu ? La perte du gène 𝘕𝘜𝘋𝘛5.
🔗 www.unil.ch/news/fr/1762...

@jourdainlab.bsky.social

That’s it, thanks for reading this long thread! 🙏

17/17

A cell-based degrader assessment platform facilitates discovery of functional NUDT5 PROTACs Targeted protein degradation (TPD) via PROTACs and molecular glues holds significant therapeutic promise but demands detailed mechanistic evaluation in live cells to fully understand compound behavior...

And a preprint from the same teams using NUDT5 degraders!
🔗 www.biorxiv.org/content/10.1...

16/17

A non-enzymatic role of Nudix hydrolase 5 in repressing purine de novo synthesis Folate metabolism is intricately linked to purine de novo synthesis through the incorporation of folate-derived one-carbon units into the purine scaffold. By investigating chemical and genetic depende...

Also from last week, a Kubicek & Huber paper on MTHFD1 & NUDT5 👇

🔗 www.science.org/doi/10.1126/...

15/17

NUDT5 regulates purine metabolism and thiopurine sensitivity by interacting with PPAT Cells generate purine nucleotides through de novo purine biosynthesis (DNPB) and purine salvage. Purine salvage represses DNPB to prevent excessive purine nucleotide synthesis through mechanisms that ...

Published last week a new paper from Ralph DeBerardinis with really cool #purinosome imaging 🧫✨

🔗 www.science.org/doi/10.1126/...

14/17

This year, a study from J. Yang links NUDT5 to thiopurine resistance in patients:

🔗 www.jci.org/articles/vie...

13/17

Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9 - Nature Biotechnology Genome-wide sgRNA libraries based on rules for on-target activity improve results of Cas9-based screens and facilitate a further refinement of on- and off-target prediction algorithms.

Same year, a screen by J. Doench & D. Root also found NUDT5 loss → 6-TG resistance:

🔗 www.nature.com/articles/nbt...

12/17

Derivation and differentiation of haploid human embryonic stem cells - Nature Haploid human embryonic stem cells have been derived from haploid oocytes, the cells maintain a normal haploid karyotype as pluripotent cells and, unexpectedly, as differentiated cells — loss-of-funct...

First, a 2016 screen by N. Benvenisty showed NUDT5 loss → 6-thioguanine resistance:

🔗 www.nature.com/articles/nat...

11/17

After our bioRxiv upload in March, THREE related #NUDT5 preprints appeared on-line! 🤯

We kept in touch with the authors and tried our best to coordinate publication. Here are some links, also to older relevant papers:

10/17

Our findings link fundamental nucleotide metabolism to clinical outcomes, highlighting #NUDT5 as a biomarker for predicting therapy efficacy in cancer, autoimmune, and viral diseases.

Huge thanks to all co-authors and funders! @snsf_ch

And now, some exciting related work 👇

9/17

This led us to propose a new mechanism ⚙️

Without NUDT5, hyperactive PPAT drains PRPP into purine synthesis, with two major consequences:
1️⃣ No PRPP left for pyrimidines synthesis
2️⃣ Nucleobase analogs can’t become toxic nucleotides 💥

8/17

Purines & pyrimidines share PRPP, the sugar for de novo synthesis. In NUDT5-KO cells, we found that PRPP levels were low ⚠️

Also, we found these cells are resistant to both purine & pyrimidine nucleoBASE analogs, but not nucleoside analogs, hinting at a key metabolic shift.

7/17

We then turned to #NUDT5, not previously tied to pyrimidine metabolism.

We found that NUDT5 binds and regulates #PPAT, the rate-limiting enzyme in #purine synthesis, and this regulation is independent of its catalytic activity!

6/17

This challenges the dogma that CoQ is required for pyrimidine synthesis! And it links to recent findings on #rhodoquinone, another CoQ-like molecule in mitochondrial electron transport.

5/17

#COQ7 is essential for CoQ synthesis, so why wasn’t it a hit? 🤔

Using lipidomics & modeling, we propose that #demethoxy-CoQ, which builds up when COQ7 is lost, can accepts e⁻ from DHODH, but not from OXPHOS complexes, thus ensuring pyrimidine synthesis!

4/17

Top hits were the 3 canonical pyrimidine synthesis enzymes + #CoQ genes 🧬

But two genes stood out: COQ7, conspicuous by its absence 👀, and NUDT5, the next strongest hit after the pyrimidine enzymes.

3/17

Genes for nucleotide synthesis are essential for cell growth, unless nucleosides for salvage are provided. This gave us an idea💡

To identify new players in pyrimidine synthesis, we ran a genome-wide CRISPR-Cas9 screen in media ± uridine, a #pyrimidine #nucleoside.
2/17

Uridine-sensitized screening identifies demethoxy-coenzyme Q and NUDT5 as regulators of nucleotide synthesis - Nature Metabolism A uridine-sensitized CRISPR-Cas9 screening identifies demethoxy-CoQ as an alternative electron acceptor in the absence of CoQ, and NUDT5 as a regulator of de novo pyrimidine synthesis via its interact...

Very excited to share the published version of our #uridine #CRISPR screen in naturemetabolism.bsky.social! 🎉

Led by Abigail Strefeler with @pagliarini-lab.bsky.social @zakbaker.bsky.social and team!

#NUDT5 #DMQ @dib-unil.bsky.social @fbm-unil.bsky.social

🔗 www.nature.com/articles/s42...
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