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Sjors Scheres

@sjorsscheres.bsky.social
3.6K followers 910 following 479 posts

Joint Head of Structural Studies at @mrclmb.bsky.social. We develop & use #cryoEM to study amyloids in neurodegeneration. #tau, #alphasynuclein, #opensoftware, #RELION. All opinions my own.

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Sjors Scheres @sjorsscheres.bsky.social · 1h
The 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! 😀
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Sjors Scheres @sjorsscheres.bsky.social · 1h
In 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.
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Sjors Scheres @sjorsscheres.bsky.social · 10/10/2026
One 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.
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Sjors Scheres @sjorsscheres.bsky.social · 06/10/2026
The 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.
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Sjors Scheres @sjorsscheres.bsky.social · 06/10/2026
Although #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.
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Sjors Scheres @sjorsscheres.bsky.social · 06/10/2026
These 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.
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Sjors Scheres @sjorsscheres.bsky.social · 06/10/2026
When 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.
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Sjors Scheres @sjorsscheres.bsky.social · 06/10/2026
Because 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.gov
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Sjors Scheres @sjorsscheres.bsky.social · 06/10/2026
In 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.
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Sjors Scheres @sjorsscheres.bsky.social · 06/10/2026
The #cryoEM structure of the induced tau filaments reveals that the structure of the seeds in replicated faithfully in this experimental system.
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Sjors Scheres @sjorsscheres.bsky.social · 06/10/2026
Seeding 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.
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Sjors Scheres @sjorsscheres.bsky.social · 06/10/2026
We 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.org
Templated seeding induces the formation of Alzheimer paired helical tau filaments in human brain organoids
The 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...
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Sjors Scheres @sjorsscheres.bsky.social · 04/10/2026
One 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.
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Sjors Scheres @sjorsscheres.bsky.social · 04/10/2026
A 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.
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Waggoner Lab @labwaggoner.bsky.social · 30/09/2026
Fibrillized 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...
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Sjors Scheres @sjorsscheres.bsky.social · 01/10/2026
I agree. Oligomers have been a distraction for too long.
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MRC Laboratory of Molecular Biology @mrclmb.ac.uk · 30/09/2026
How 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 🧪
Alzheimer's and corticobasal degeneration tau filaments induce distinct pathologies in mouse brains, with corresponding cryo-EM images and structural models.
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Sjors Scheres @sjorsscheres.bsky.social · 30/09/2026
Our 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. 🥳
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Sjors Scheres @sjorsscheres.bsky.social · 24/09/2026
Over 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.
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TW @twesq.bsky.social · 20/09/2026
this is fantastic and I learned something new
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Sjors Scheres @sjorsscheres.bsky.social · 21/09/2026
A lot has happened in amyloid structural biology since 2015...
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Sjors Scheres @sjorsscheres.bsky.social · 15/09/2026
Michel 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.com
Postdoctoral Scientist | Neurobiology | Dr Michel Goedert | LMB 2842 - Cambridgeshire job with MRC Laboratory of Molecular Biology | 12864505
Postdoctoral 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...
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Sami Chaaban @sami-c.bsky.social · 10/09/2026
Excited to share that the Chaaban Lab will be opening in January at the Crick!
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Sjors Scheres @sjorsscheres.bsky.social · 30/08/2026
The 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.
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Sjors Scheres @sjorsscheres.bsky.social · 30/08/2026
The 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.
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Sjors Scheres @sjorsscheres.bsky.social · 27/08/2026
🥳
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Sjors Scheres @sjorsscheres.bsky.social · 25/08/2026
This should be fun for the computer-minded among us who find joy in supporting science . 😍
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Sjors Scheres @sjorsscheres.bsky.social · 19/08/2026
We are now developing agents to execute #relion workflows, but to get those expert user decisions in non-linear workflows right is not so easy!
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Sjors Scheres @sjorsscheres.bsky.social · 19/08/2026
I 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?
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Sjors Scheres @sjorsscheres.bsky.social · 18/08/2026
Not a problem: a bonus! This is why #OpenSoftwareAcceleratesScience. Are there plans to maintain your interface in the long run?
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Bronwyn Lucas @bronwynalucas.bsky.social · 12/08/2026
Now 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.org
A fast diagonalization algorithm to enable singular value decomposition of large matrices for efficient template matching
Many 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...
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Sjors Scheres @sjorsscheres.bsky.social · 01/08/2026
Good luck Morgan! We shall expect great things.
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MRC Laboratory of Molecular Biology @mrclmb.ac.uk · 30/07/2026
Congratulations 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
Chris Russo
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Sjors Scheres @sjorsscheres.bsky.social · 27/07/2026
Where is all the money going? Every day we read about massive cuts by @ukri.org, but their budget wasn't cut.
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Sjors Scheres @sjorsscheres.bsky.social · 27/07/2026
I 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.com
AstraZeneca 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
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Bronwyn Lucas @bronwynalucas.bsky.social · 25/07/2026
New 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.org
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...
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Sjors Scheres @sjorsscheres.bsky.social · 25/07/2026
With half of Europe on fire, can our politicians finally get serious about the climate crisis? Burnham could look to the Spanish PM for inspiration.
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Joe Greener @jgreener64.bsky.social · 24/07/2026
I 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
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Sjors Scheres @sjorsscheres.bsky.social · 24/07/2026
Some 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.com
The ICC is far from perfect – but it can hold the likes of Trump, Putin and Netanyahu to account | Steve Bloomfield
The US threat to shut down the international criminal court is chilling: actions must have consequences, says Steve Bloomfield, former international editor of the Observer
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Sjors Scheres @sjorsscheres.bsky.social · 08/07/2026
Sorry, 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.google
Count 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
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MRC Laboratory of Molecular Biology @mrclmb.ac.uk · 03/07/2026
LMB 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
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Sjors Scheres @sjorsscheres.bsky.social · 02/07/2026
With 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? 🤔
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Sjors Scheres @sjorsscheres.bsky.social · 28/06/2026
And 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.
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Sjors Scheres @sjorsscheres.bsky.social · 28/06/2026
Now, 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...
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Sjors Scheres @sjorsscheres.bsky.social · 28/06/2026
I 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.
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Sjors Scheres @sjorsscheres.bsky.social · 28/06/2026
Another 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.
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Sjors Scheres @sjorsscheres.bsky.social · 25/06/2026
I'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? 🤔
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Toula Drimonis @mtltoula.bsky.social · 15/06/2026
Ten years after Brexit. The front page of @theindependent.bsky.social
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Sjors Scheres @sjorsscheres.bsky.social · 06/06/2026
Still a thing! 😉
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Sjors Scheres @sjorsscheres.bsky.social · 06/06/2026
I wear a lot of orange! 🧡
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