Sjors Scheres @sjorsscheres.bsky.social · 1hThe method is based on cool ideas. In effect, it blurs the distinction between structure prediction and structure determination. That probably also means one should carefully rethink validation, i.e. how would one detect erroneous solutions? Exciting times! 😀 020
Sjors Scheres @sjorsscheres.bsky.social · 1hIn general, when optimising a difficult target we have a choice to use prior information to restrain the set of solutions, or to keep some of it aside for validation. This approach is a very interesting exercise in how far one can go with using the available prior information in AlphaFold. 110
Sjors Scheres @sjorsscheres.bsky.social · 10/10/2026One problem with this approach is that our main tool to detect issues, the quality of the map, is gone. That is especially important for weak SNR data sets, where Einstein will be happy to emerge from noise. 3190
Sjors Scheres @sjorsscheres.bsky.social · 06/10/2026The study with the organoids was spearheaded by Mehtap Bacioglu in Maria Grazie Spillantini's group. The work on primary cultures was led by Melissa Huang, who was previously in Will McEwan's group and who is now with us, in Michel Goedert's group. 000
Sjors Scheres @sjorsscheres.bsky.social · 06/10/2026Although #cryoEM structures of the seeded aggregates remain to be confirmed, STED microscopy reveals that different seeds lead to distinct morphologies of the seeded aggregates inside the cultures, which will be interesting for our future studies on the distinct downstream effects of tau strains. 120
Sjors Scheres @sjorsscheres.bsky.social · 06/10/2026These results confirm that also in murine primary cultures one can faithfully replicate the structure of the #AD seeds! The AAV system provides lots of flexibility in these seeding experiments. E.g. one can choose to overexpress either 3R or 4R human tau and seed with 3R or 4R tauopathies. 120
Sjors Scheres @sjorsscheres.bsky.social · 06/10/2026When using limited amounts of seeds, we could see density for the methionine at position 337, confirming that we had indeed solved the structure of the seeded aggregates. However, we could also solve the structure of the seeds when using more seeds. This is an important warning for future studies. 110
Sjors Scheres @sjorsscheres.bsky.social · 06/10/2026Because we worried about solving the structure of the seeds, we performed a control experiment where we overexpressed V337M mutant tau and solved the structure. We had previously shown that this mutant still forms PHFs in human brains. pubmed.ncbi.nlm.nih.gov/40044789/pubmed.ncbi.nlm.nih.govChecking your browser - reCAPTCHA 100
Sjors Scheres @sjorsscheres.bsky.social · 06/10/2026In murine primary cortical cultures, we need overexpression of full-length human tau to get sufficient tau aggregation within the life-span of the cells. But then we also see robust seeded aggregation. 100
Sjors Scheres @sjorsscheres.bsky.social · 06/10/2026The #cryoEM structure of the induced tau filaments reveals that the structure of the seeds in replicated faithfully in this experimental system. 110
Sjors Scheres @sjorsscheres.bsky.social · 06/10/2026Seeding wildtype human organoids with #Alzheimer brain-derived tau filaments, we see increasing tau pathology over a nine-month period. This does not happen when we do not seed, or we seed a tau-knockout organoid. 110
Sjors Scheres @sjorsscheres.bsky.social · 06/10/2026We have 2 new preprints on @biorxivpreprint.bsky.social that describe reconstitution of #Alzheimers paired helical filaments in experimental model systems: one in human brain organoids and one in murine primary cultures. www.biorxiv.org/content/10.6... www.biorxiv.org/content/10.6...biorxiv.orgTemplated seeding induces the formation of Alzheimer paired helical tau filaments in human brain organoidsThe prion concept postulates that seeded aggregation results in the recruitment of soluble protein monomers and their assembly into amyloid filaments with the same structures as those of the seeds. He... 14617
Sjors Scheres @sjorsscheres.bsky.social · 04/10/2026One practical step could be to limit CVs to a maximum of N papers, where the importance of each paper gets explained. N could vary for different purposes. 141
Sjors Scheres @sjorsscheres.bsky.social · 04/10/2026A cultural change in how we measure/perceive scientific productivity, away from numbers of papers, towards more meaningful measures, would be helpful for many aspects of science and how we organise it. 251
Reposted by Sjors ScheresWaggoner Lab @labwaggoner.bsky.social · 30/09/2026Fibrillized tau protein, a feature of neurodegenerative disorders, acts as a prion-like template to induce misfolding in healthy tau @nature.com @sjorsscheres.bsky.social www.nature.com/articles/d41... www.nature.com/articles/s41... 031
Sjors Scheres @sjorsscheres.bsky.social · 01/10/2026I agree. Oligomers have been a distraction for too long. 010
Reposted by Sjors ScheresMRC Laboratory of Molecular Biology @mrclmb.ac.uk · 30/09/2026How does neurodegeneration spread across the brain? 🧠 @sjorsscheres.bsky.social, Michel Goedert & Masata Hasegawa’s groups have demonstrated that human misfolded tau filaments act as a molecular template for prion-like propagation in the mouse brain. mrclmb.ac.uk/news-events/... #LMBResearch 🧪 02313
Sjors Scheres @sjorsscheres.bsky.social · 30/09/2026Our adventures into #proteinfolding: GuideFlip designs flexible molecular interactions by discrete flow matching to design sequence & structure together! Grateful for funding by Love Tito's (@titosvodka.bsky.social) and the @ukri.org. 🥳 02513
Sjors Scheres @sjorsscheres.bsky.social · 24/09/2026Over the last week I have had separate discussions with three people being disillusioned by how bad their colleagues are at their job. Large organizations seem worse. I wonder whether having line managers work together with their people, instead of just leading from above, is a good solution. 282
Reposted by Sjors ScheresTW @twesq.bsky.social · 20/09/2026this is fantastic and I learned something new 563232436
Sjors Scheres @sjorsscheres.bsky.social · 21/09/2026A lot has happened in amyloid structural biology since 2015... 041
Sjors Scheres @sjorsscheres.bsky.social · 15/09/2026Michel Goedert and myself are looking for two postdocs to work on #cryoEM and #masspec of #alphasynuclein filaments from neurodegenerative disease. Come join our bubbly and friendly team at the @mrclmb.ac.uk in lovely Cambridge, UK. www.nature.com/naturecareer...nature.comPostdoctoral Scientist | Neurobiology | Dr Michel Goedert | LMB 2842 - Cambridgeshire job with MRC Laboratory of Molecular Biology | 12864505Postdoctoral Scientist Salary £42,694 per annum Fixed term, 3 years MRC Laboratory of Molecular Biology, Cambridge, UK To work in the group of Dr M... 01728
Reposted by Sjors ScheresSami Chaaban @sami-c.bsky.social · 10/09/2026Excited to share that the Chaaban Lab will be opening in January at the Crick! 77514
Sjors Scheres @sjorsscheres.bsky.social · 30/08/2026The skills needed will change. I find AI helpful to focus on what you want to write, not how. The thinking process of finding the best story (which remains critical) becomes a conversation with AI instead of iteratively rewriting text that got stuck in a local minimum. 120
Sjors Scheres @sjorsscheres.bsky.social · 30/08/2026The use of AI should not be conflated with letting AI write nonsense. Using AI to improve a text is great, especially for inexperienced writers. We all hate the slop. Detection of AI is not the problem to solve. 100
Sjors Scheres @sjorsscheres.bsky.social · 25/08/2026This should be fun for the computer-minded among us who find joy in supporting science . 😍 021
Sjors Scheres @sjorsscheres.bsky.social · 19/08/2026We are now developing agents to execute #relion workflows, but to get those expert user decisions in non-linear workflows right is not so easy! 150
Sjors Scheres @sjorsscheres.bsky.social · 19/08/2026I struggle to see the novelty here. Isn't the agent just trying out available workflows? How much long-horizon reasoning and expert decision-taking is required for those? 130
Sjors Scheres @sjorsscheres.bsky.social · 18/08/2026Not a problem: a bonus! This is why #OpenSoftwareAcceleratesScience. Are there plans to maintain your interface in the long run? 110
Reposted by Sjors ScheresBronwyn Lucas @bronwynalucas.bsky.social · 12/08/2026Now on Arxiv: arxiv.org/abs/2608.10029 Led by grad student Matthew Giammar and collaborator Alex Strang, we provide a fast algorithm to calculate a low rank approximation to large (>100 million row) matrices with high fidelity that will accelerate template matching.arxiv.orgA fast diagonalization algorithm to enable singular value decomposition of large matrices for efficient template matchingMany computational problems possess the following three features: (1) the problem could be solved efficiently if a linear operator could be diagonalized, (2) direct diagonalization is infeasible due t... 2228
Sjors Scheres @sjorsscheres.bsky.social · 01/08/2026Good luck Morgan! We shall expect great things. 000
Reposted by Sjors ScheresMRC Laboratory of Molecular Biology @mrclmb.ac.uk · 30/07/2026Congratulations to Chris Russo, Group Leader in the LMB’s Structural Studies Division, who has been awarded the 2026 K. H. Kuo Award for Distinguished Scientist in Biological Electron Microscopy. www.bsc.org.cn/KuoSymposium... #LMBintheNews 0243
Sjors Scheres @sjorsscheres.bsky.social · 27/07/2026Where is all the money going? Every day we read about massive cuts by @ukri.org, but their budget wasn't cut. 151
Sjors Scheres @sjorsscheres.bsky.social · 27/07/2026I am quite happy taking medicines that I know were tested rigourously for efficacy and safety at the speed that takes... www.theguardian.com/business/202...theguardian.comAstraZeneca boss urges western drugmakers to move at ‘Chinese speed’Europe and US risk being outpaced on innovation, as happened in the car industry, warns Pascal Soriot 020
Reposted by Sjors ScheresBronwyn Lucas @bronwynalucas.bsky.social · 25/07/2026New preprint from the lab! Led by graduate student @lainahall.bsky.social we show a new method to thin cells for cryo-EM imaging with minimal damage. www.biorxiv.org/content/10.6...biorxiv.orgOptimized cryo-FIB milling strategy to generate thin, minimally damaged biological lamellaeFocused 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... 14517
Sjors Scheres @sjorsscheres.bsky.social · 25/07/2026With half of Europe on fire, can our politicians finally get serious about the climate crisis? Burnham could look to the Spanish PM for inspiration. 2122
Reposted by Sjors ScheresJoe Greener @jgreener64.bsky.social · 24/07/2026I have often seen Microsoft software spread within organisations due to IT and procurement people being "captured" by effective lobbying and sales pitches. Microsoft software is not particularly good, safe or cheap, and researchers benefit from having choice over what they use. @ukri.org 061
Sjors Scheres @sjorsscheres.bsky.social · 24/07/2026Some inside the @ukri.org wish to push @microsoft.com software too far down into research. This is a risk that didn't work out well for the ICC! @ukri.org should focus on funding good science rather than homogenise for the sake of homogenisation. www.theguardian.com/commentisfre...theguardian.comThe ICC is far from perfect – but it can hold the likes of Trump, Putin and Netanyahu to account | Steve BloomfieldThe US threat to shut down the international criminal court is chilling: actions must have consequences, says Steve Bloomfield, former international editor of the Observer 060
Sjors Scheres @sjorsscheres.bsky.social · 08/07/2026Sorry, I usually don't do politics on here, but this is so funny. You have to give it to the Brits: their sense of humour can be very powerful. share.google/oaD90DqioZAe...share.googleCount Binface on Clacton byelection: ‘I didn’t know old Farage was going to self-detonate’‘Perhaps it’s all a fever dream,’ suggests parody candidate, expected to be Reform leader’s only challenger for seat 1100
Reposted by Sjors ScheresMRC Laboratory of Molecular Biology @mrclmb.ac.uk · 03/07/2026LMB spinout company @trimtechtx.bsky.social has now raised $47M in seed funding. Building on research by Leo James and @w-mcewan.bsky.social, TRIMTECH Therapeutics will utilise targeted protein degradation to develop novel neurodegeneration treatments. Read more here: shorturl.at/LeTaZ #LMBintheNews 052
Sjors Scheres @sjorsscheres.bsky.social · 02/07/2026With all this talk about decentralisation in UK politics this week, I wonder when @ukri.org will be up. Wouldn't it be great to devolve power to the research councils, whose expert staff care deeply about their area of science? 🤔 131
Sjors Scheres @sjorsscheres.bsky.social · 28/06/2026And once one of these systems becomes the norm, my trainees will want to write papers that maximise that score, so the influence of such a system on the literature will be immense. I just think AI is nowhere near where it needs to be to have such large effects on the scientist enterprise. 170
Sjors Scheres @sjorsscheres.bsky.social · 28/06/2026Now, I am comfortable with such arguments being part of a healthy scientific discussion between scientists, but AI-generated slop is taken as given truth by way too many people... 150
Sjors Scheres @sjorsscheres.bsky.social · 28/06/2026I suspect everyone will be happy about positive reviews, but negative reviews will be more difficult. I put in one of our papers and it identified major "gaps" that I fundamentally disagree with, but which rest on arguments others have published on multiple occasions. 140
Sjors Scheres @sjorsscheres.bsky.social · 28/06/2026Another thing that worries me is that this "oracle of preprints" will be biased towards those who publish more. Science is not a democracy, and the less prolific voices may turn out to be right. I suspect that an AI-average of the literature will find it hard to make those independent judgements. 140
Sjors Scheres @sjorsscheres.bsky.social · 25/06/2026I'm worried authors will quickly adapt how they claim novelty in their papers to get good AI-generated scores. I have always loved a beautifully understated paper. Will we see even less of those? 🤔 281
Reposted by Sjors ScheresToula Drimonis @mtltoula.bsky.social · 15/06/2026Ten years after Brexit. The front page of @theindependent.bsky.social 42634253