Jan-Hannes Schaefer

I'll try and keep you updated. The story continues.

@maxewilkinson.bsky.social fun little cryo-EM puzzle. I am still pushing the resolution to let ModelAngelo do its magic. My guess was either a common amyloid binder like SAP or an intermediate of Lysozyme-amyloids...

Thanks @olibclarke.bsky.social I must have overlooked that one and should give it a go.

Reprocessed ALys Amyloids from EMPIAR-11785 Fändrich Lab

GitHub - schaefer-jh/CS-amyloids: Amyloid-processing with cryo-SPARC Amyloid-processing with cryo-SPARC. Contribute to schaefer-jh/CS-amyloids development by creating an account on GitHub.

CS workflow for easy testing: github.com/schaefer-jh/...

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...

‪We had a fantastic time hosting the first Functional Amyloid Meeting @ DESY! #FFFatDESY2025 #FunctionalFibrilFriends
landaulabcssb.bsky.social

Initial attempt at replicating in relion (parameters in next post). This is for Aca2-RNA, using a 100k subset of the 2D-classified particles (no prior 3D cleanup).

A 1-class ab initio in relion, then local refinement in relion (1.8deg searches+blush) gives a nominally 3.3Å map; 3.5 Å w/out blush.

❄️ NEW PRE-PRINT ❄️ Happy to see our latest work online. Here we present a super simple solution to the preferred orientation problem in single particle cryo-EM: the use of ultrasonic excitation during vitrification! Details in the 🧵 below... #cryoEM #structuralbiology

Another successful approach to the same problem as HR-HAIR! 🤩 I wonder if a combo might be worth a try - use one frequency band to get perfectly centered particles using 2DTM, then re-estimate orientations using HR-HAIR with a non-overlapping frequency band?

A great resource. One highlight for me is: "One of the best things about structural biology is visualizing what you are discovering."

This one is a bit of a departure from the usual and definitely a work in progress!

We found that by using ab initio reconstruction at very high res, in very small steps, we could crack some small structures that had eluded us - e.g. 39kDa iPKAc (EMPIAR-10252), below.

Read on for details... 1/x

Congrats @olibclarke.bsky.social, great work. I've tried PKA and failed. SPA processing is still an art and lesson in persistence.

Magellon has taken off to explore your cryo-EM data! Now out in @iucrj.iucr.org doi.org/10.1107/S205... Congrats to all involved!

I often go back to this striking study: doi.org/10.1126/scie...

Uninspired while making figures? Search no more. #science #art

Thanks for sharing @olibclarke.bsky.social. I wonder if many more "hollow" complexes are co-purified with binding-partners. Let's all put more datasets on EMPIAR to revisit processing with new creative approaches like Oli's.

Congrats @olibclarke.bsky.social and team. Such a great idea! Would you share some more CS parameters for the processing-geeks? Maybe via a CS workflow .json?

Our work on "Mechanistic adaptation of the metazoan RabGEFs Mon1-Ccz1 and Fuzzy-Inturned" is now out in Science Advances! Congrats to all involved. www.science.org/doi/10.1126/...

Was lucky to see this presented at the NYC cryoEM meeting earlier this year - super cool stuff!

Covalently constrained ‘Di-Gembodies’ enable parallel structure solutions by cryo-EM - Nature Chemical Biology Disulfide-based dimerization of modified identical and heterologous nanobody scaffolds enables higher-order assembly for high-resolution cryo-electron microscopy structure determination that is widely...

Di-Gembodies (dimerized nanobodies) for improved and duplexed CryoEM of small and challenging targets!

A collaboration of @cmd.ox.ac.uk, STRUBI, @diamondlightsource.bsky.social, @rosfrankinst.bsky.social

Out now in Nature Chemical Biology @natchembio.nature.com

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

Thanks Oli, absolutely. Maybe using a resolvability metric like the Q-score? The EMDB auto-validation Q-score could be more visible and added to the RCSB PDB report along with the clashscore.

Good eye. Re-processed AP2 EMPIAR-11604.

Thanks for highlighting this great story! @landerlab.bsky.social and I wrote a PREreview about the preprint: prereview.org/reviews/1581...

Lithium deficiency and the onset of Alzheimer’s disease - Nature Lithium has an essential role in the brain and is deficient early in Alzheimer’s disease, which can be recapitulated in mice and treated with a novel lithium salt that restores the physiological level.

New @nature.com
The possibility that lithium deficiency is a driver of Alzheimer's disease. Experimental model shows Li depletion impedes amyloid clearance, and repletion in humans could be achieved with low doses
nature.com/articles/s41...

CryoSift – An accessible and automated CNN-driven tool for cryo-EM 2D class selection

Check out our new preprint from the @landerlab.bsky.social, Stagg-Lab and Cianfrocco-Lab: CryoSift - An accessible and automated CNN-driven tool for cryo-EM 2D class selection www.biorxiv.org/content/10.1...
Happy testing: cryosift.org #cryoEM #CNN

Sub-3 Å resolution protein structure determination by single-particle cryo-EM at 100 keV Cryoelectron microscopy (cryo-EM) has transformed structural biology by providing high-resolution insights into biological macromolecules. We report s…

Now out in Structure: Paper on high-resolution #cryoEM using the 100 kV Tundra cryo-TEM by Dimple Karia, Adrian Koh, @abhaykot.bsky.social, @lingboyu.bsky.social, @landerlab.bsky.social and many others. Happy to have contributed to this effort. Check it out:
www.sciencedirect.com/science/arti...

Frontiers | Effect of Brisk Walking on Health-Related Physical Fitness Balance and Life Satisfaction Among the Elderly: A Systematic Review Background: Although the elderly frequently engages in brisk walking as a form of exercise, little has been reported in the literature about the effect of br...

Great! Quantity matters, but quality seems to be important too: Short but brisk walking for all the office folks. doi.org/10.3389/fpub...

AlphaFold - A practical guide AlphaFold - A practical guide

Recently I learnt that EMBL-EBI has a free online course about AlphaFold — how it works, strengths and limitations, how to use it — and it's very good!

There are also little quizzes and interactives.
www.ebi.ac.uk/training/onl...

Yet another great case study! Maybe most symmetric assemblies are not? And helical assemblies next @structurabio.bsky.social ?