New preprint! In collaboration with the Akbey lab at UPitt, we solved the cryo-EM structure of FapB, an accessory functional amyloid in Pseudomonas biofilms. It forms a cross-β-solenoid closely related to the major fibril FapC, and the two cross-seed each other. doi.org/10.64898/202...
Jan-Hannes Schaefer
Jan-Hannes Schaefer
@jhschaef.bsky.social
Structural Biology to the rescue. Postdoc at Scripps Research. https://jhschaefer.de/ ❄️🔬 🎹⛳
471 followers503 following82 posts
Turns out it's "A hair in the Soup." Tailocins are recurrent contaminants in ex vivo amyloid extraction. We've updated the preprint and provided actionable recommendations to avoid overinterpreting contaminants. doi.org/10.64898/202...
Bacteriophage tails co-enrich with ex vivo amyloids from amyloidosis patients. Cryo-EM reveals Siphoviridae tail tube protein in ALys and AL amyloid extract. Do phages interact with human amyloids? @landerlab.bsky.social @nanigrotjahn.bsky.social & Kelly Lab #cryoEM #b3d doi.org/10.64898/202...
Transthyretin doesn't exclusively unfold the way we thought. Under lysosomal pH (4-5), or with certain mutations, it takes an alternative route through a more expanded tetrameric transition state. And kinetic stabilizers work less well on it. @scripps.edu doi.org/10.1073/pnas...
To resolve the 55 kDa Transthyretin, we used Docyl maltoside to overcome preferred orientation. A route established in @landerlab.bsky.social - doi.org/10.64898/202...
Transthyretin doesn't exclusively unfold the way we thought. Under lysosomal pH (4-5), or with certain mutations, it takes an alternative route through a more expanded tetrameric transition state. And kinetic stabilizers work less well on it. @scripps.edu doi.org/10.1073/pnas...
Jan-Hannes Schaefer reposted
Imaging large fields-of-view at high resolution in cryo-ET with square beam montaging https://www.biorxiv.org/content/10.64898/2026.08.27.747605v1
Thanks for highlighting our work. I hope it helps the community. Let me know if the Protocol works for you and what @cryosparc.bsky.social could improve.
Presenting the first article in our new 'Protocols' category: Helical reconstruction of amyloids in cryoSPARC #Amyloids #CryoEM #HelicalReconstruction doi.org/10.1107/S205...
Jan-Hannes Schaefer reposted
Jan-Hannes Schaefer reposted
Some questions for our structural biology community: What protocols do you think would be useful to have? Do you prefer to watch step-by-step videos, or follow written instructions? Of course, not everything has to be a video, but certain workflows are simply best documented on video #protocols
A new type of article for Acta F: Protocols The purpose of this new category is to provide to the reader procedures that are sufficiently detailed so other researchers can reproduce the described workflow. Find out more in 'Show me how it's done: introducing Protocols': doi.org/10.1107/S205...
Bacteriophage tails co-enrich with ex vivo amyloids from amyloidosis patients. Cryo-EM reveals Siphoviridae tail tube protein in ALys and AL amyloid extract. Do phages interact with human amyloids? @landerlab.bsky.social @nanigrotjahn.bsky.social & Kelly Lab #cryoEM #b3d doi.org/10.64898/202...
New paper out in @actacrystf.iucr.org! We benchmarked cryoSPARC for amyloid helical reconstruction: ease of use over RELION, but amyloid-specific development still needed & software interoperability remains a problem. @landerlab.bsky.social Kelly Lab @scripps.edu doi.org/10.1107/S205...
Jan-Hannes Schaefer reposted
We are pleased to release an update to this pre-print! Includes (1) proof-of-principle experiments on ultrasonic excitation during plunge vitrification, (2) cryo-ET characterisation of the effect, (3) and insights into grid/ice quality following ultrasonic excitation during vitrification.
Jan-Hannes Schaefer reposted
This is the kind of work, published today, that should be fully supported and prioritized at the highest level. Currently, there is no vaccine vs the Ebola Bundibugyo virus, the source of a major outbreak www.pnas.org/doi/10.1073/...
Jan-Hannes Schaefer reposted
Try this new online training game from Leandro F. Estrozi designed for newcomers in structural biology, with a focus on cryo-EM and cryo-ET map interpretation: rico.ibs.fr/helixplo...
In our new work from the Kelly, Ye & @landerlab.bsky.social , we link ATTR cardiomyopathy to microangiopathy. Increased capillary permeability exposes components of the vascular basement membrane to misfolded TTR. Work led by Joe Donnelly. #amyloidosis #cryoem #b3d doi.org/10.1161/JAHA...
We identified the maltoside detergent DM as an effective and easy solution to address preferred orientation in cryo-EM. Helped me switch from graphene grids. Special congrats to Maria Rafiq! @landerlab.bsky.social @nanigrotjahn.bsky.social @wisemanlab.bsky.social #cryoEM doi.org/10.64898/202...
Jan-Hannes Schaefer reposted
We're excited to announce the beta-release of #RELION-5.1! 🥳 This release has important updates on our #amyloid processing pipeline, as described in this preprint: doi.org/10.64898/202... There are also some tweaks for #teamtomo. #OpenSoftwareAcceleratesScience
Great to see one of my PhD projects out on bioRxiv. We report "A dual sensor regulates P-glycoproteins structural plasticity." Congrats to Michael Kamel for doing the heavy lifting from @arnemoeller.bsky.social & Urbatsch Lab. doi.org/10.64898/202... #b3d #cryoEM
For obvious reasons, we need a Paceometer! #endroadrage doi.org/10.1017/S193...
Jan-Hannes Schaefer reposted
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...
Jan-Hannes Schaefer reposted
Jan-Hannes Schaefer reposted
Since last year, I've been making a RELION GUI that supports viewing, navigating and running jobs in a way completely compatible with the original RELION pipeline. Now it's working nicely for both SPA and tomography! Please try it out - github.com/hanjinliu/hi...
Thanks, I guess we all needed this.
Our new paper (with @biotay.bsky.social) is out and on the cover story of @currentbiology.bsky.social !!!! Veronika, a Carinthian mountain cow flexibly uses a “multi-purpose tool” to scratch herself. A video and more information will follow in the comments. www.cell.com/current-biol...
In our new preprint, we show how fibril-dynamics of signaling component TIRAP supports sensitive & fast sensing of endotoxin LPS. Congrats to co-lead @arthurfelker.bsky.social. @piehlerlab.bsky.social @arnemoeller.bsky.social #TLR #cryoEM #blender doi.org/10.64898/202...
Thanks to @actacrystf.iucr.org for highlighting our smart 2D selection tool CryoSift. You can test it yourself here cryosift.org
New interview alert! We had a chat with Mike Cianfrocco, Scott Stagg and Jan-Hannes Schäfer about their CryoSift tool – details in the thread. www.youtube.com/watch?v=ROlc...
Jan-Hannes Schaefer reposted
Jan-Hannes Schaefer reposted
Just installed Doppio on our Linux machine. This is awesome work making relion more accessible and easy to run. I haven't tried submitting jobs yet but it is already making our live easier! I met Matt Iadanza at the CZI but I guess he doesn't have bluesky to tag!
At some point, Doppio will replace relion's gui. Already you can do more in Doppio than in relion! 🤩
CryoSift is now out @actacrystf.iucr.org doi.org/10.1107/S205... Thanks to all involved. Happy processing!
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
Jan-Hannes Schaefer reposted
Lauren Alexandrescu et al.: `Mix-it-up': accessible time-resolved cryo-EM on the millisecond timescale #ElectronMicroscopy #CryoEM #TimeResolvedStudies ... #IUCr https://journals.iucr.org/paper?S2052252525008838
Jan-Hannes Schaefer reposted
Excited to share a new chapter of my scientific journey in Chris Russo's group — developing a way to freeze proteins faster than they diffuse, paving the way for cryo-EM without air–water interface damage.
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
Jan-Hannes Schaefer reposted
🚀 Introducing fully automated data processing for repeat-target #cryoEM. Using new tools in #CryoSPARC, it is now possible to obtain resolutions & map quality equal to or better than manual processing, with zero user intervention. Preprint: www.biorxiv.org/content/10.1...
Thanks @odedrechavi.bsky.social. Even without explicit coverage of structural biology, it did a great job as Reviewer #0 on my latest preprint. Highly recommend www.qedscience.com
BIG ANNOUNCEMENT📣: I haven’t been this excited to be part of something new in 15 years… Thrilled to reveal the passion project I’ve been working on for the past year and a half!🙀🥳 (thread 👇)
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...
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...
Jan-Hannes Schaefer reposted
We had a fantastic time hosting the first Functional Amyloid Meeting @ DESY! #FFFatDESY2025 #FunctionalFibrilFriends landaulabcssb.bsky.social
Jan-Hannes Schaefer reposted
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.
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.
Jan-Hannes Schaefer reposted
❄️ 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
Overcoming Preferred Orientation in Cryo-EM With Ultrasonic Excitation During Vitrification https://www.biorxiv.org/content/10.1101/2025.09.14.676144v1
Jan-Hannes Schaefer reposted
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?
Improved cryo-EM reconstruction of sub-50 kDa complexes using 2D template matching www.biorxiv.org/content/10.1101/2025.09.11.675606v1 #cryoEM
A great resource. One highlight for me is: "One of the best things about structural biology is visualizing what you are discovering."
Structural bioinformatics is incredibly powerful on its own or when paired with theory or experiment. One of the PDB's superpowers isn’t from one structure, but comparing many to uncover folds, binding sites, and subtle conformational shifts. chemrxiv.org/engage/chemr...
Jan-Hannes Schaefer reposted
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
High-resolution ab initio reconstruction enables cryo-EM structure determination of small particles https://www.biorxiv.org/content/10.1101/2025.09.08.674935v1
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!
Exited to share my first PostDoc contribution! Like Magellan explored the globe, you can explore your cryoEM data with Magellon. Congrats to all involved. Scott Stagg Lab & Michael Cianfrocco Lab @landerlab.bsky.social www.biorxiv.org/content/10.1... 🌎❄️🔬
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/...
New preprint. Mechanistic Plasticity of the RabGEFs Mon1-Ccz1 and Fuzzy-Inturned. Showing how TLD-RabGEFs adapt to different cellular functions. Congrats to first author @stephanwilmes.bsky.social from the Kümmel Lab. #cryoEM #openscience @arnemoeller.bsky.social doi.org/10.1101/2025...
Jan-Hannes Schaefer reposted
Jan-Hannes Schaefer reposted
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...
Jan-Hannes Schaefer reposted
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...
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
Jan-Hannes Schaefer reposted
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...