Tomas Pascoa

Figure 1. Cryo-EM of abundant protein complexes in native membranes.

Figure 2. Cryo-EM of membrane proteins in vesicles.

Figure 3. 3D reconstruction of V-ATPase in native synaptic vesicle membranes.

Figure 4. Generation of membrane vesicles for structure determination of proteins in their native lipid bilayer.

I've written a review on what I think is an extremely exciting direction in cryo-EM:

Cryo-EM of endogenous membrane proteins in their native lipid bilayer

Open access in Quarterly Reviews of Biophysics:
doi.org/10.1017/S003...

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 🧵

Check out this cool thread on the latest preprint by Gaurav Kumar, @james-r-barrett.bsky.social, @phaips.vd.st from our lab and colleagues, dissecting the physics of Rubisco condensates!

You're in for some stunning #cryoET of the pyrenoid - in Chlamy, of course 😉

Congrats to all involved!

Please share!
My group at @zmbp-tuebingen.bsky.social is offering a post-doctoral position (4 years). We look for a structural biologist with experience in Cryo-EM/Cryo-ET to investigate the mechanisms of host invasion by pathogenic fungi. Deadline February 28th!
uni-tuebingen.de/universitaet...

LLOMe has long been used to study lysosomal damage, yet how it works has remained a mystery.
Using cryo-electron tomography, we show it forms amyloid structures inside lysosomes that mechanically rupture membranes – revealing a new paradigm for lysosomal failure.

🔗 doi.org/10.64898/202...

#CryoET

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

We are thrilled to share our new pre-print on the molecular anatomy of nuclear proteasome in human sperm cells! #In-cellcryo-ET + #SPA + #LM! @piotrkolata.bsky.social @a-dsantos.bsky.social, @tomdendooven.bsky.social!! doi.org/10.64898/202...

IsoNet2 determines cellular structures at submolecular resolution without averaging https://www.biorxiv.org/content/10.64898/2025.12.09.693325v1

Happy to share our fun team-up with @centriolelab.bsky.social & @stearnslab.bsky.social to reveal the architecture of the mammalian centriole’s Distal Ring 🛟. Very cool multiscale integration of #UExM 📏🔬with #CryoET ❄️🔬. Congrats to @ebertiaux.bsky.social & @computingcaitie.bsky.social #TeamTomo 🧪

CryoET of microbes inside an animal organ? Yes it’s possible! Check out our new preprint showing how we did it! What an amazing collaboration with amazing scientists who made this possible!

Prohibitins aren’t hanging out just anywhere in the membrane — they prefer the 💁‍♀️💎✨VIP section💅🪩🥂

Lab all-star @mmedina300kv.bsky.social maps these microdomains using cryo-ET + surface morphometrics.

s/o to #teamtomo #cryoET co-authors
@hamid13r.bsky.social
@attychang.bsky.social
@baradlab.com

Icecream: High-Fidelity Equivariant Cryo-Electron Tomography Cryo-electron tomography (cryo-ET) visualizes 3D cellular architecture in near-native states. Recent deep-learning methods (CryoCARE, IsoNet, DeepDeWedge, CryoLithe) improve denoising and artifact cor...

Our colleagues Vinith Kishore and Valentin Debarnot from the @ivandokmanic.bsky.social lab have come up with an amazing deep learning tool for denoising and filling the missing wedge in #cryoET data. I'm pleased to introduce Icecream🍧

Hey #TeamTomo …would you like to try some 🍦ICECREAM!? Our @unibas.ch colleagues over at the @ivandokmanic.bsky.social lab have developed a stunningly effective tool to de-noise and de-wedge your tomograms. The contrast and details will give you brain freeze! 🍨❄️🤯

Please try, we need feedback 🧪🧶🧬🔬

Check out our new preprint on an integrated pipeline combining in situ #cryo-ET with MALDI #MSImaging for single-cell identification and classification from previously analysed EM-grids.
Link: www.biorxiv.org/content/10.1...

Amyloid reconstructions from cryoSPARC

Helical Reconstruction of Amyloids in cryoSPARC?
We present guidelines, limitations & future perspectives for processing amyloids in cryoSPARC @structurabio.bsky.social.
Great collaboration of the Kelly Lab and @landerlab.bsky.social #cryoEM #amyloid www.biorxiv.org/content/10.1...

Streptophyte algae go #TeamTomo with @thanahartmann.bsky.social!

Time for a thread!🧵 How different is the molecular organization of thylakoids in “higher” plants🌱? To find out, we teamed up with @profmattjohnson.bsky.social to dive into spinach chloroplasts with #CryoET ❄️🔬. Curious? ..Read on!

#TeamTomo #PlantScience 🧪 🧶🧬 🌾
elifesciences.org/articles/105...
1/🧵

We have a preprint of a book chapter for you: Structural Analysis of Membrane Proteins in Cell-Derived Microvesicles.

We describe how to image membrane proteins in mid-sized vesicles using cryo-electron tomography

zenodo.org/records/1717...

These results are truly impressive! But I do worry that #cryoEM is moving into a phase where progress is made by optimizing parameter settings for black box programs. The devil is often in the details, and I am not sure how this could be implemented in #relion, as stated, without more info.

Sub-cellular chemical mapping in bacteria using correlated cryogenic electron and mass spectrometry imaging

Congrats Hannah Ochner and authors on this important paper! Strong collaboration with @kiranrpatil.bsky.social

www.biorxiv.org/cgi/content/...
@mrclmb.bsky.social @wellcometrust.bsky.social

Leopard-EM: An extensible 2DTM package to accelerate in situ structural biology The ability to generate high-resolution views of cells with cryogenic electron microscopy (cryo-EM) can reveal the molecular mechanisms of biological processes in their native cellular context. The re...

First pre-print from the Lucas Lab led by Matthew Giammar and @joshdcryoem.bsky.social online today! We develop a new, extensible Python implementation of 2DTM and apply it to build pixel size optimization, constrained search and characterize molecular motions in situ www.biorxiv.org/content/10.1...

If you are thinking about the future of structural biology, we are too! Our two cents (Jürgen Plitzko and I) just got published online here: authors.elsevier.com/sd/article/S...

Optimal tilt-increment for cryo-ET Cryo-electron tomography (cryo-ET) enables high-resolution, three-dimensional imaging of cellular structures in their native, frozen state. However, image quality is limited by a trade-off between ang...

More great cryo-ET benchmarking work from my colleagues Maarten Tuijtel, Tomáš Majtner, Beata Turoňová, & @becklab.bsky.social: Systematic study of how tilt increment choice affects downstream TM & STA. Preprint has the optimally balanced tilt increment. #TeamTomo www.biorxiv.org/content/10.1...

🚨 Imagine a bacterium that refuses to follow the textbook:
It grows as tangled filaments, divides unevenly, reshapes its own membranes… and even builds grappling hooks.
Meet Litorilinea aerophila — and here’s why it blew our minds.

New preprint: In situ Architecture of #Plasmodesmata.

Using #cryoET, #AlphaFold & proteomics, we uncover the native organization of plant intercellular nanopores.

🔗 doi.org/10.1101/2025...

🧪🧵1/n
#teamtomo #PlantScience #Physcomitrium #Arabidopsis #cryoEM

hot (well, cold) off the press! ❄️

well done @glynnca.bsky.social & @michaelgrange.bsky.social & fabulous co-authors 👏🏼

#teamtomo #cryoET

A practical look at cryo-electron tomography image processing: Key considerations for new biological discoveries Cryo-electron tomography (cryo-ET) enables 3D visualization of complex biological environments without the need for purification, thereby preserving t…

Happy to say that my Current Opinion in Structural Biology article came out today. I hope it helps to guide to you in using cryo-ET to make new biological discoveries!

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

CryoET tomogram with the gap junction (green), ribosomes (cyan) and microtubules (pink)

In our latest preprint on bioRxiv, we present the in situ structure of
the human gap junction at 14 Å resolution using cryo-ET.

The structure provides a blueprint for investigating how connexin
regulation shapes intercellular communication in health and disease.

Structural and functional analysis of the Mycobacterium tuberculosis MmpS5L5 efflux pump presages a pathway to increased bedaquiline resistance Bedaquiline, an antitubercular drug that targets ATP-synthase, is a key component of a new oral drug regimen that has revolutionized the treatment of multi drug resistant tuberculosis. Clinical bedaqu...

Bedaquiline resistance driven by the MmpS5L5 efflux pump is threatening the drug regimens used to treat MDR-TB.

In our new preprint, we used structural and genetic approaches to better understand how MmpS5L5 effluxes bedaquiline and how future resistance may evolve. 🧵🔽

#TBsky #MicroSky #TB

Interactions between TTYH2 and APOE facilitate endosomal lipid transfer - Nature The Tweety homologue TTYH2 is identified as the lipid transfer mediator for APOE-containing lipoproteins.

Interesting new structure of the Tweety protein TTYH2 complexes with delipidated ApoE
www.nature.com/articles/s41...