James A. Letts

Finding one mutation that improves a protein is hard. Finding five that work together is exponentially harder.

Today in @science.org, Hsu and Konermann labs present MULTI-evolve, a lab-in-the-loop framework that does it in just one machine learning-guided round.

Cryogenic electron tomography by the numbers: Charting underexplored lineages in structural cell biology pubmed.ncbi.nlm.nih.gov/41706896/ #cryoEM

New paper from my group in @science.org : "A small polymerase ribozyme that can synthesise itself and its complementary strand" www.science.org/doi/10.1126/...
Outstanding work by @edogia.bsky.social

Long in the making, but happy to present the Chlamydomonas chlororibosome!
Cryo-ET🔬reveals a large new domain on the small subunit, built from multiple extensions in conserved ribosomal proteins.
bioRxiv 📖: shorturl.at/q44tG
This suggests greater chlororibosome diversity than expected!
1/n 🧵

Very happy to contribute a short section to this Methods in Molecular Biology regarding Eugleozoa. We describe large-scale Paradiplonema papillatum cultivation using carboys.
Great work by postdoc Dong Woo Shin and a game changer for biochemical and structural work!
link.springer.com/book/10.1007...

Thank you @mollyherring.bsky.social for the stunning showcase 😍

Like what you see? Come ExM with us! Let’s flood the internet with microbial marvels 🦠

#ProtistsOnSky #MicroEvoSky 🧪🔬🌍

@dudinlab.bsky.social @centriolelab.bsky.social @moorefound.bsky.social @embl.org @erc.europa.eu @embo.org

Zombosomes, large vesicles with cell-like qualities, can spread alpha-synuclein protein clumps from astrocytes to other astrocytes, neurons, and lab-grown brain tissues.

Learn more: https://scim.ag/4qSd1vP

Expansion Microscopy Has Transformed How We See the Cellular World | Quanta Magazine How physically magnifying objects using a key ingredient in diapers has opened an unprecedented view of the microbial world.

Expansion microscopy may be the hi-res hero that many biologists have been craving.

LAST CALL! Come join me at Glasgow University for evolutionary structural biology! We have fully positions.

Computational Postdoc:
www.jobs.gla.ac.uk/job/research...

Structural Postdoc:
www.jobs.gla.ac.uk/job/research...

Technician:
www.jobs.gla.ac.uk/job/technici...

Check out our new preprint! We uncover the full molecular mechanism of rotavirus membrane penetration and cytosolic escape using cryo-ET, live-cell imaging, and single-molecule assays. (1/3)

🔗 biorxiv.org/content/10.6...

🚀 CryoSPARC v5.0 BETA is here!

We’re excited to deploy another major #CryoSPARC release to help enable and accelerate #cryoEM data analysis. v5 has a redesigned underlying software system and many new features - highlights in thread!

Full changelog: cryosparc.com/updates/v5.0.0

Single-cell genomics reveals complex microbial and viral associations in ciliates and testate amoebae - Nature Communications Protist microbiomes are poorly understood. Here, the authors analysed single protist cells to profile their microbiomes and viromes showing that these tiny eukaryotes serve as environmental hubs for hidden bacterial symbionts and diverse giant viruses.

Single-cell genomics reveals complex microbial and viral associations in ciliates and testate amoebae

#Symbiosis #Protists #GiantViruses

Atomic resolution cryo-EM at 200 keV Atomic resolution in cryo-electron microscopy was first demonstrated six years ago. This was accomplished using 300 kV electron microscopes equipped with new hardware that provided narrower energy spr...

👀 👀

Atomic-resolution #cryoEM at 200 keV.
www.biorxiv.org/content/10.6...

Comparison of the cytoskeletal architectures of Toxoplasma and Chromera flagellates using ExM.

Isadonna Tengganu and Ke Hu develop transfection and ExM protocols for Chromera velia, enabling direct comparisons with its parasitic apicomplexan relative, Toxoplasma gondi.
journals.biologists.com/jcs/article/...

Scientists have gotten good at blocking enzymes to treat disease. Now can they speed them up? - News Enzymes are the molecular machines that power life; they build and break down molecules, copy DNA, digest food, and drive virtually every chemical reaction in our cells. For decades, scientists have d...

For decades, scientists have designed drugs to slow down or block enzymes, but Tarun Kapoor wondered if tackling some diseases requires the opposite approach.

We spoke with Kapoor about why speeding up an enzyme is so difficult, and how his team is cracking this problem.

See the full Q&A here:

It is so exciting to see our LEA proteins playing a role in solving this insane structure. Amazing work to the authors!

The #ChlamyDataset is on the cover of @cp-molcell.bsky.social 🖼️🥰!

Read @lifeonthewedge.bsky.social's great thread🧵 for the inside scoop🍨 on all the #TeamTomo developments already made possible since these 1829 tomos hit EMPIAR 🧪 🧶🧬

For more, here's the old preprint thread:
bsky.app/profile/cell...

This was a really fun and interesting Molecule of the Month to do! Check out the article to see even more elaborate RNA-only structures.

Medina, Chang et al. of the @nanigrotjahn.bsky.social lab introduce a new method based on the Surface Morphometrics pipeline to measure global and local thicknesses of organellar #membranes from cellular cryo-electron tomography data. rupress.org/jcb/article/...

#CryoET

New preprint out! Using ~75k environmental OTUs + 77 fossil calibrations, we reconstructed a Proterozoic timeline of eukaryote evolution. Our results show crown eukaryotes were already diversifying >1.6 Ga, long before the first undisputed fossils (~1.05 Ga).
🔗 DOI: www.biorxiv.org/content/10.6...

A free, open-access library of high-quality organism illustrations for science communication We create vector graphics of model organisms and emerging biological research organisms to enhance our publications. We’re sharing these editable graphics under a CC0 license for other scientists to...

A free, open-access library of high-quality organism illustrations for science communication

It’s out! Using cryo-ET in Dicty cells, we take a fresh in situ look at vaults. Surprisingly, we uncover vaults associated with ER and NE membranes, and find that many vaults enclose ribosomes in defined orientations, opening new avenues to their cellular function! www.biorxiv.org/lookup/conte...

A Divergent Cytochrome c in Malaria Parasites with an Anomalously Low Redox Potential Eukaryotic cytochrome (cyt) c is a highly conserved mitochondrial protein central to cellular respiration, featuring a covalently attached hexacoordinate heme whose redox potential is tuned by axial H...

Happy to share a new preprint exploring the unusual biochemistry of a "weirdly" diverged cytochrome c in malaria parasites that exemplifies a lineage common to many apicomplexan parasites. @uofubiochem.bsky.social @uuhsresearch.bsky.social @uofutahcihd.bsky.social
www.biorxiv.org/content/10.6...

Finally, we’ve solved a long-standing mystery: what tintinnid shells are actually made of:
A new class of biomaterial formed by remarkable structural proteins unique to tintinnids.
A major milestone after 3 years of work! Read about it in our preprint: doi.org/10.64898/202...
#ProtistsOnSky

Final version is out! Our large-scale cryo-ET dataset 🔬 of Chlamydomonas reinhardtii 🦠 is now published in @cp-molcell.bsky.social

Huge collaborative effort! So glad to see the community already using it to develop new resources & tools.

Check it out here: shorturl.at/z4i4c
#CryoEM #CryoET

New @jgp.org study from Lopez-Mateos, Narang, & @vyy-sf.bsky.social @ucd-physiology.bsky.social reveals potential of #DeepLearning methods to model multiple states of human voltage-gated sodium channels and their interactions with β-subunits and calmodulin. rupress.org/jgp/article/...

#IonChannels

Just on time for the holidays! Happy to share the published version of the discovery of leptophytes, a new deep-branching and widespread group of microalgae based on plastid MAGs (ptMAGs). Now with additional support from a mitochondrial MAG (mtMAG) of leptophytes.
www.nature.com/articles/s41...

very unusual - a tRNA regulated anion channel

Our latest paper on the molecular mechanisms of XPF-ERCC1 recruitment to SLX4-dependent DNA repair pathways has been published! Congratulations to first author Junjie Feng, and a heartfelt thank you to all our collaborators for their contributions to this study!
www.nature.com/articles/s41...

AlphaFold predictions are valuable hypotheses and accelerate but do not replace experimental structure determination - Nature Methods An analysis of AlphaFold protein structure predictions shows that while in many cases the predictions are highly accurate, there are also many instances where the predicted structures or parts of pred...

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