With Cryo-ET/EM, the macromolecules we study (and biological questions we ask) are SNR-limited. Here, we share Nilas, a low-voltage milling method named after thin sea ice. Nilas produces thin (sub 50 nm in places!), minimally damaged lamellae. biorxiv.org/content/10.64898/2026.07.21.739890v1

Optimized cryo-FIB milling strategy to generate thin, minimally damaged biological lamellae

Focused ion beam (FIB)-milling has been adapted to thin frozen cells for visualization of macromolecular structures in situ with cryogenic electron microscopy. However, only a few large and abundant c...

biorxiv.org

XLPP in practice www.biorxiv.org/content/10.6...

High Accuracy Fluorescence Guided Focused Ion Beam Milling https://www.biorxiv.org/content/10.64898/2026.05.11.724418v1

MissAlignment is out!!! Our new software that improves reference-free tilt series alignment by mimicking human intuition. Check out Dimitry's beautiful thread for a quick summary! And the preprint for more details: www.biorxiv.org/content/10.6... The program: github.com/warpem/miss-...

Dimitry Tegunov@dtegunov.bsky.social · 3mo ago

We're super excited to share MissAlignment: a new ML-based approach to reference-free tilt series alignment, spearheaded by @martenchaillet.bsky.social. We think it's going to make your cryo-ET life a lot better. Preprint: www.biorxiv.org/content/10.6... Code: github.com/warpem/miss-... 🧶 Thread:

📣 Physicists and engineers: apply your experimental skills to biology! Join the group of Katerina Naydenova @imprs-lm.bsky.social for a #PhD to develop new technologies that enable answering fundamental biological questions. Apply NOW!

Now out in full form. Again, a big thanks to #teamtomo and @alisterburt.bsky.social for developing the infrastructure to build this on. journals.iucr.org/d/issues/202...

Leopard-EM: an extensible 2D template-matching package to accelerate in situ structural biology

In situ cryo-EM coupled with 2D template matching (2DTM) holds the potential to visualize the cellular structureome in context, but further developments are required to make this a reality. We describ...

journals.iucr.org

Chris Russo and Anastasiia Gusach have developed a new method to prepare #cryoEM samples that avoids protein damage during freezing Read more: www2.mrc-lmb.cam.ac.uk/a-new-method... #LMBResearch

We are happy to announce that we will have two new scientific groups led by Andrija Sente and Katerina Naydenova soon! If you are interested to join their lab as a PhD Student apply at our @imprs-lm.bsky.social www.imprs-lm.mpg.de/index.php/jo...

Improved cryo-EM reconstruction of sub-50 kDa complexes using 2D template matching www.biorxiv.org/content/10.1101/2025.09.11.675606v1 #cryoEM

Happy for this to be out! We have documentation and tutorials here. Please give it a try and let us know what you think. lucaslab-berkeley.github.io/Leopard-EM/

Bronwyn Lucas@bronwynalucas.bsky.social · 11mo ago

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...

Pulsed-electron illumination does not reduce beam damage for imaging biological macromolecules www.biorxiv.org/content/10.1101/2025.07.29.667395v1 #cryoEM

@joshdcryoem.bsky.social will also be giving a talk about his prior work as a PhD student with Chris Russo developing strategies to take advantage of the reduced radiation damage at liquid Helium temperatures for cryo-EM. You can find their paper here: www.pnas.org/doi/abs/10.1...

Reducing the effects of radiation damage in cryo-EM using liquid helium temperatures | PNAS

The physical limit in determining the atomic structure of biological molecules is radiation damage. In electron cryomicroscopy, there have been num...

pnas.org

If you are going to M&M, also see postdoc @joshdcryoem.bsky.social's poster about tilted vs untilted data collection for in situ structural biology www.sciencedirect.com/science/arti....

To tilt or not to tilt? Strategies for in situ cryo-EM data collection

Recent breakthroughs in single-particle cryogenic electron microscopy (cryo-EM) and protein structure prediction have transformed our ability to resol…

sciencedirect.com

Check out our recent review discussing the merits of tilt series vs single micrographs for in situ cryo-EM! www.sciencedirect.com/science/arti...

To tilt or not to tilt? Strategies for in situ cryo-EM data collection

Recent breakthroughs in single-particle cryogenic electron microscopy (cryo-EM) and protein structure prediction have transformed our ability to resol…

sciencedirect.com

At the 2024 IMC meeting, Richard Henderson laid down a challenge. Design a #TEM single-particle #cryoEM lens with 1mm Cc at 100kV. I'm thrilled to reveal our new Arxiv preprint delivering a fully retrofittable pole-piece swap out for the @jeoleurope.bsky.social 1400 TEM. arxiv.org/abs/2505.11458

In the Bay Area? Love computational cryo-EM/ET? Come join us for the first edition of FrostByte - a meeting for the local computational cryo-EM methods community! Details and registration at frostbyte-cryoem.github.io Thanks to @joshdcryoem.bsky.social and Ariana Peck for help organizing!

For a shorter read, @mrclmb.bsky.social and @science.org also have articles about the helium story. www.science.org/content/arti...

Ultracool microscopy yields a sharper look at proteins

After years of frustration, researchers learn how to sharpen molecular images with liquid helium

science.org

MRC Laboratory of Molecular Biology@mrclmb.ac.uk · last yr.

A colder frontier in cryo-EM 🧪🔬 Chris Russo’s group, inc. Joshua Dickerson, adapted #cryoEM to work at liquid helium temperatures (13 kelvins), where every frame captured contains more information than the equivalent using liquid nitrogen (81 kelvins). Read more: tinyurl.com/mwwcunkc #LMBResearch

After years parked at a Polara, I’m excited to share that my PhD work is finally out! We figured out why imaging at liquid helium temperatures wasn’t working—and how to fix it. 🔗 www.pnas.org/doi/10.1073/...

Reducing the effects of radiation damage in cryo-EM using liquid helium temperatures | PNAS

The physical limit in determining the atomic structure of biological molecules is radiation damage. In electron cryomicroscopy, there have been num...

pnas.org

Exploring shaped focused ion beams for lamella preparation https://www.biorxiv.org/content/10.1101/2025.04.01.646235v1

In-Situ High-Resolution Cryo-EM Reconstructions from CEMOVIS https://www.biorxiv.org/content/10.1101/2025.03.29.646093v1

Foam film vitrification for cryo-EM https://www.biorxiv.org/content/10.1101/2025.03.10.642366v1

I've been wanting to see a paper using off-axis electron holography for low-dose biological imaging since the start of my PhD. Spatially resolved charge measurements👌

cryoEM papers@cryoempapers.bsky.social · 2y ago

Off-axis electron holography of unstained bacteriophages: Toward electrostatic potential measurement of biological samples pubmed.ncbi.nlm.nih.gov/39818354/

Kexin Zhang et al.: A new statistical metric for robust target detection in cryo-EM using 2D template matching #3DReconstructionAndImageProcessing #SingleParticleCryoEM #Imaging @umassboston...#IUCr https://journals.iucr.org/paper?S2052252524011771

A new statistical metric for robust target detection in cryo-EM using 2D template matching

A novel statistical metric for 2D template matching (2DTM), the 2DTM p-value, has been developed to improve the detection of targets in cryo-EM images under various imaging and sample conditions, particularly for smaller and aspherical targets.

journals.iucr.org

Laser Flash Melting Cryo-EM Samples to Overcome Preferred Orientation biorxiv.org/cgi/content/short/2024.11.21.624652v1