Genetically encoded manipulation of ATP/ADP ratio in human cells uncovers proteomic and physiological signatures of energy stress Ekvik et al. genetically introduced an exogenous ATP-consuming enzyme into human cells in order to study the direct effects of energy stress in vivo. This genetic approach offers flexibility and specificity inaccessible through conventional drug-based models of energy stress. The intervention produced well-established as well as unexplored energy stress responses.

Genetically encoded manipulation of ATP/ADP ratio in human cells uncovers proteomic and physiological signatures of energy stress #chembiol

Few people are aware of how much progress has been made against cancers.

Leukemia is probably the most striking example.

Before the 1970s, most children affected by leukemia would soon die from it.

Now, most children in rich countries survive.
ourworldindata.org/childhood-le...

5-Azacytidine incorporation into mRNAs disrupts translation and induces ribosome collisions www.biorxiv.org/content/10.64898/2026.03...

Image of News in focus article from Nature entitled "How bioRxiv changed the way biologists share ideas - in numbers"

The impact of bioRxiv in numbers

@richardsever.bsky.social

Non-canonical role for glutahtione in supporting tumours by acting as a reservoir of amino acids @nature.com @fabiohecht.bsky.social @uofr.bsky.social
www.nature.com/articles/s41...

In Cells and Outside of Them

What goes on in a collection of assays in purified proteins can be very different from what happens in a living well. Case in point:

Proteomic profiling reveals pleiotropic antimetabolite activity of triciribine in acute lymphoblastic leukemia www.biorxiv.org/content/10.64898/2026.03...

Microscope images of Ryugu samples collected from the first and second touchdown sites of the Hayabusa2 mission, respectively. Credit: JAXA / JAMSTEC

The complete set of nucleobases found in terrestrial DNA and RNA — adenine, guanine, cytosine, thymine and uracil — have been detected in samples returned from the asteroid Ryugu, according to research in Nature Astronomy. go.nature.com/3P9A9YN 🔭 🧪

Inference of Cancer Drug Cross Resistance Using Only Single-Drug Exposure Data www.biorxiv.org/content/10.64898/2026.03...

Macrophage-specific Ak4 regulates mtDNA synthesis, through which it controls mitochondrial biogenesis and mtROS levels and, subsequently, bacterial killing
rupress.org/jem/article/... @jem.org

FEBS Press Cytarabine is a key therapy for acute myeloid leukaemia (AML), but its efficacy is limited by the dNTPase SAMHD1, which hydrolyses its active metabolite. Screening nucleotide biosynthesis inhibitors ...

Happy to share the second paper from the group this year, out in @moloncology.bsky.social

Another story about the dNTPase & drug resistance factor SAMHD1 and our attempts to find ways to suppress its activity in cancer cells 👇

febs.onlinelibrary.wiley.com/doi/10.1002/...

@scilifelab.se @ki.se

FEBS Press Cytarabine is a key therapy for acute myeloid leukaemia (AML), but its efficacy is limited by the dNTPase SAMHD1, which hydrolyses its active metabolite. Screening nucleotide biosynthesis inhibitors ...

Happy to share the second paper from the group this year, out in @moloncology.bsky.social

Another story about the dNTPase & drug resistance factor SAMHD1 and our attempts to find ways to suppress its activity in cancer cells 👇

febs.onlinelibrary.wiley.com/doi/10.1002/...

@scilifelab.se @ki.se

With Eugene Koonin, we propose a concept of “the selfish ribosome”, under which evolution of life is viewed as a ribosomal takeover, where the ribosome evolved to consume most of the cell’s resources, while other cellular componentry ensures the propagation of the ribosome. arxiv.org/abs/2602.23268

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...

This is correct

My objection to LLMs is not about form but substance: writing is about the only thing a PI actually produces. LLM coaching makes writing yet another task where we're managers instead of makers. It's the final victory of the managerial model – same reason why I'm also against outsourcing research

This is absolutely the opposite of how I understand academic writing

Allosteric targeting with antiviral nucleotide analogues allows fine-tuning of SAMHD1 dNTPase activity SAMHD1 is a deoxyribonucleoside triphosphate (dNTP) hydrolase that controls intracellular dNTP pools and plays diverse roles in human health and disease. Notably, this enzymatic activity also confers ...

Excited to share the latest research from the group!

We have a new paper out in @asbmbjournals.bsky.social led by our first PhD student!

Here we look at the enzyme SAMHD1, a key player in dNTP metabolism and chemotherapy resistance

www.jbc.org/article/S002...

cc @scilifelab.se @ki.se

🧵

20 new Technology Development Projects funded as call strengthens collaboration across and beyond SciLifeLab SciLifeLab recently decided on 20 Technology Development Projects (TDPs) for funding in the latest TDP call. TDPs are projects aimed at developing new technologies, methods or workflows, often as…

20 new Technology Development Projects funded as call strengthens collaboration across and beyond SciLifeLab. 🧪

A goal of the TDPs is that the developed technologies will eventually be offered as new services to the user community.

More & list of projects ↓

Large-scale mapping of environmental-genetic interactions illustrates the dynamic nature of cell-cycle and DNA repair regulation To date, genetic interaction (GI) maps in the context of environmental perturbations have been limited to yeast studies. Herken et al. present five human GI maps that reveal how the landscape of genes...

This work shows that gene function is not fixed but dynamically shaped by a cell’s environment, and that mapping those shifts can reveal biology invisible to single-condition screens.

Download the full paper: www.cell.com/molecular-ce...

Congratulations to Sonomi Yamaguchi for her paper at @nature.com. Sonomi discovered Clover defense and explained how nucleotide signals control each step of viral sensing, immune regulation, and viral restriction – named for her beautiful "four-leaf" structures 🍀

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

A Pan-Cancer Ex Vivo Drug Screen Atlas for Functional Precision Oncology www.biorxiv.org/content/10.64898/2026.02...

Recognizing dUTPase as a mitotic factor essential for early embryonic development www.biorxiv.org/content/10.64898/2026.01...

Can check out the full paper here (there is a couple more interesting things in there...)

👇👇👇
www.jbc.org/article/S002...

Very grateful to the team & collaborators

And of course the funders - particularly Cancerfonden and Barncancerfonden - together with doctoral funding from @ki.se

Cheers!

Model from the paper. In the presence of GTP analogues, SAMHD1 forms homotetramers that are catalytically competent, but display reduced catalytic activity with distinct kinetic profiles compared to those containing the endogenous activator GTP

We think this differential activity can be largely explained by distinct kinetic profiles that deviate from the usual with this enzyme

But what we're quite excited about is the implication that we can fine-tune activity of SAMHD1 via non-natural allosteric site ligands

Figure from the paper showing SAMHD1 dNTPase activity against different dNTPs when activated with GTP or GTP analogues acyclovir-/ganciclovir-triphosphate. Activity towards different dNTPs differ greatly. In particularly, dCTP hydrolysis is abolished.

We found these analogues can activate SAMHD1, binding to the allosteric site with a higher affinity than the physiological ligand GTP, and promote formation of a catalytically-competent tetramer

However, these tetramers have vastly (!) different activity profiles...

Figure from the paper detailing the allosteric activation of SAMHD1, which requires nucleotide binding at two distinct allosteric sites to generate the active tetramer. The first allosteric site is specific for guanine nucleotides. Also shown are the chemical structures of GTP and GTP-analogues acyclovir- and ganciclovir-triphosphate

SAMHD1 is allosterically regulated by nucleotides with one of the allosteric sites being specific for the guanine nucleotide GTP

So here we asked how analogues of GTP - specifically the active metabolites of anti-viral agents acyclovir and ganciclovir - work as allosteric effectors

Cartoon showing bio-activation of a nucleoside analogue cancer drug into its triphosphate metabolite, which is subsequently hydrolysed by the enzyme SAMHD1, rendering it ineffective.

SAMHD1 is a dNTP hydrolase that we've previously shown can deactivate a bunch of cancer drugs whose active metabolites mimic dNTPs (i.e., nucleoside analogues)

So one thing we are looking at in the lab is how we can control the activity of this enzyme with small molecules

Allosteric targeting with antiviral nucleotide analogues allows fine-tuning of SAMHD1 dNTPase activity SAMHD1 is a deoxyribonucleoside triphosphate (dNTP) hydrolase that controls intracellular dNTP pools and plays diverse roles in human health and disease. Notably, this enzymatic activity also confers ...

Excited to share the latest research from the group!

We have a new paper out in @asbmbjournals.bsky.social led by our first PhD student!

Here we look at the enzyme SAMHD1, a key player in dNTP metabolism and chemotherapy resistance

www.jbc.org/article/S002...

cc @scilifelab.se @ki.se

🧵

We carried out a mechanistic study on how the PCBP1 protein destabilizes i-motifs. Understanding these interactions helps clarify fundamental mechanisms that control genome function.
Grateful for the long-term support we have received! @kawresearch.bsky.social @mbb-umu.bsky.social
rdcu.be/e2pIv