James Davies

Fungal-derived cellobiose metabolic pathway fuels T cells to bypass intratumoral glucose competition Solid tumors harbor immunosuppressive microenvironments that inhibit tumor-infiltrating lymphocytes (TILs) through the voracious consumption of glucos…

"Nobody will care about your work about sugar metabolism and transporters in Neurospora crassa"

Nobody can predict what can happen with your work.

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

*one of the bottlenecks

CH•••S hydrogen bonds drive molecular recognition of ergothioneine by the microbial transporter Alkyl CH•••S hydrogen bonding interactions enable selective transport of the antioxidant ergothioneine into bacterial cells.

#microsky

Transporters matter and they’re always fun to work with

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

Eukaryogenesis in light of an expanded catalogue of Asgard genomes. a, Simplified, scaled timeline spanning from before the Last Asgard archaea Common Ancestor (LAsCA) to today. Thin bands mark predicted time ranges of relevant events (for example, GOE), thicker bands represent processes (for example, eukaryogenesis), and brackets indicate the period shown in b. The timeline further highlights milestones, including potential early eukaryotic fossils60 and the modern-day co-occurrence of Heimdallarchaeia and Alphaproteobacteria observed in this study (interaction likely originated earlier).

Fig. 1 | Expanded genomic diversity of Asgard archaea. a, Maximum-likelihood phylogeny based on 47 non-ribosomal markers (NM47)using the WAG + C10 + R4 model with 100 nonparametric bootstrap pseudoreplicates, including 869 Asgardarchaeota MAGs and 309 outgroup genomes. The blue branches (lower right) indicate the new Asgardarchaeota classes, Ranarchaeia, and the recently proposed Asgardarchaeia4. The concentric rings denote (in to out): the predicted genome size, metabolic guilds based on Pfam clustering, sampling locations, and black stars on the outside mark MAGs added by this study. Asgard, Asgardarchaeia; Atabey, Atabeyarchaeia; Baldr, Baldrarchaeia; Frey/Jord, Frey/Jordarchaeia; Gerd, Gerdarchaeales; Heimdall, Heimdallarchaeaceae; Hel, Helarchaeales; Hermod, Hermodarchaeia; Hod, Hodarchaeales; Kari, Kariarchaeaceae; Loki, Lokiarchaeales; Njord, Njordarchaeales; Odin, Odinarchaeia; Ran, Ranarchaeia; Sif, Sifarchaeia; Thor, Thorarchaeia; Wukong, Wukongarchaeia. b, SR4-recoded phylogeny of the same genome set inferred with the model GTR + C60 + G and 100 nonparametric bootstrap pseudoreplicates (Methods). This updated catalogue constitutes a large increase in the medium- to high-quality publicly available genomes (completeness >50% and contamination and redundancy <10%) with 65.3% from the Guaymas Basin and 34.7% from the Bohai Sea. The encircled numbers represent MAGS added by this study. The scale bars in bothsubpanels represent the average number of substitutions per site.Map created in BioRender; Appler, K. https://biorender.com/147ieoc(2025).

Our work is published today: ‘Oxygen metabolism in descendants of the archaeal-eukaryotic ancestor’. This was a huge effort lead by @katyappler.bsky.social. Extremely grateful to have been a part of this amazing project! 😊🦠🧬

Links: www.nature.com/articles/s41...
www.nature.com/articles/s41...

I’ve officially started my lab at Monash University! 🎉

We’re diving into #cellgrowth and #lysosome biology, through the lens of molecular #structure and mechanism.

I’m thrilled to say that PhD student scholarships are available—so please share widely and get in touch if you’re interested. 🤩

A tour de force!

The Biochemical Society 2025 Awards. International Award, Professor Renae Ryan, University of Sydney. Includes photo of Prof Ryan and Biochemical Society awards logo.

Internationally renowned as one of the leaders in neurotransmitter transport research, don't miss Professor Renae Ryan (@renaeryan.bsky.social) present her #BiochemSoc International Award Lecture at Membrane #Proteins Conference 2026! 🧪

Beginning 2026 with a flipping good paper🚀 OSCA/TMEM63 proteins do double duty: they’re ion channels and mechanically activated lipid scramblases helping reshape membranes and survive mechanical stress. 👏 @yiechanglin.bsky.social @charlesdcox.bsky.social doi.org/10.1038/s414...

Countdown to Lorne Proteins 🏖️ Session 6: Invited speakers Nieng Yan, Tsinghua University, on the structural pharmacology of Voltage-gated sodium channels; closing with Simon Newstead, University of Oxford, on plasma membrane polyamine transporters in chronic pain.

🔗 www.lorneproteins.org

First inhibitor of a bacterial two-partner secretion system. Two-partner secretion system transporter proteins (TpsB) are widely conserved across Gram-negative pathogens. TpsB family proteins secrete exoprotein virulence factors that perform a myriad of functions such as adhesion and immune modulation. Despite their incredible importance in bacterial infectious disease, TpsB inhibitors have not yet been discovered. Here, we describe a potent inhibitor of FhaC, a TpsB protein produced by Bordetella spp . FhaC secretes the exoprotein FhaB that is essential for the establishment of whooping cough. We designed a peptide called P1 that we predicted would prevent substrate binding and lock FhaC in a secretion-inactive state. Simulations and biochemical assays supported our hypothesis and identified interactions important for P1 binding to FhaC. Strikingly, we observed that the peptide strongly inhibited FhaB secretion from clinical isolates and broadly reduced correlates of virulence. Together, this work provides a strong case for further development of a novel class of anti-TpsB anti-virulence compounds. ### Competing Interest Statement The authors have declared no competing interest. National Institute of Allergy and Infectious Diseases, R21AI180112

💊 We are excited to share our preprint that describes an inhibitor of the widespread and highly conserved Two-Partner Secretion (TPS) system that is critical for Gram-negative pathogens to export a multitude of diverse virulence factors.

(1/6)

www.biorxiv.org/content/10.6...

⛔ Defined how the bronchodilator ipratropium binds OCTN2 and inhibits Na⁺-dependent carnitine transport.

Big thanks to the team who made this work possible: Jack Zeng, Chelsea Briot, Simon Brown, @renaeryan.bsky.social , and Alastair Stewart.

🧂 Identified an unusual Na⁺ binding site in an aqueous cavity separate from the carnitine site.

🧬 Mapped known SPCD variants onto the structures to rationalise how mutations can impair substrate binding, gating, and Na⁺ coupling.

Using cryo-EM and electrophysiology, we:

🧊 Captured three key conformational states: inward-facing ligand-free, carnitine/Na⁺-bound occluded, and inward-facing ipratropium-bound.

⚡ Showed that transport is electrogenic and Na⁺-dependent, consistent with Na⁺-coupled carnitine uptake.

OCTN2 mediates carnitine uptake across the plasma membrane. Carnitine is essential for importing long-chain fatty acids into mitochondria for energy production. Variants cause systemic primary carnitine deficiency (SPCD), a rare disorder that can lead to serious metabolic and cardiac complications.

Structural basis of sodium ion-dependent carnitine transport by OCTN2 Nature Communications - Carnitine uptake by OCTN2 supports fatty acid metabolism. Here, authors report cryo-EM structures of human OCTN2, revealing the mechanism of sodium ion-dependent carnitine...

Our paper on the human carnitine transporter OCTN2 (SLC22A5) is out in @natcomms.nature.com! We solved structures of OCTN2 in multiple states and explored how carnitine transport is Na⁺-dependent, providing a framework for understanding SPCD disease causing variants and drug interactions.

🚨My lab is hiring a postdoc!🚨
If you’re interested in working out the mechanism and physiological impact of bacterial lipid transport processes then please apply!

Job advert is here: tinyurl.com/4swddfda

Get in touch by email (c.mulligan@kent.ac.uk) for informal enquiries

Please repost!
Thanks!

Thrilled to announce a new @natcomms.nature.com paper led by Alastair Stewart and team @victorchang.edu.au with contributions from @mcdevittlab.bsky.social
Using #cryoEM we discovered unique features of the #Pseudomonas aeruginosa ATP synthase including an unexpected role for #zinc in the complex 🦠🔬

Congratulations to first author Michael Newton-Vesty and thanks to all of our collaborators across New Zealand, Australia, and Italy who made this possible.

This work extends our understanding of TRAP transporters beyond sialic acid systems, revealing how these sodium-coupled machines recognise and move a different class of substrates.

Functional assays show that the system is Na⁺-driven, and that transport relies on a partner substrate-binding protein (IseP) for delivery and specificity. The membrane transporter alone does not efficiently transport isethionate, so binding is effectively outsourced to its soluble partner.

Structural basis of isethionate transport by a TRAP transporter from a sulfate-reducing bacterium Newton-Vesty et al. used a megabody fiducial to determine the cryo-EM structure of an isethionate TRAP transporter, revealing the substrate and Na+-binding sites. Transport is dependent on Na+ and the...

Check out our new paper:
🔗 www.cell.com/structure/fu...

We explored how sulfate-reducing bacteria import isethionate, a sulfur-containing molecule found in the environment and produced by microbes in the human gut. We captured a structure of the IseQM TRAP transporter in a substrate-bound state.

Structural basis of isethionate transport by a TRAP transporter from a sulfate-reducing bacterium Newton-Vesty et al. used a megabody fiducial to determine the cryo-EM structure of an isethionate TRAP transporter, revealing the substrate and Na+-binding sites. Transport is dependent on Na+ and the...

#microsky finally a TRAP transporter that is *not* the Neu5Ac-transporting SiaPQM ;-)

www.cell.com/structure/fu...