Marcin J. Suskiewicz

In memory of Professor Israel Silman (1935–2025) Click on the article title to read more.

I was saddened to hear (with delay) of Israel Silman ('Sili')'s passing. A kind and very intelligent protein biochemist whom I was lucky to briefly work with.

A near-complete map of human cytosolic degrons and their relevance for disease

We measured degron potency of >200,000 30-residue tiles from >5,000 human proteins, and trained a model to predict degrons from sequence

Led by @vvouts.bsky.social in @rhp-lab.bsky.social

doi.org/10.1126/scia...

I am excited to share a new review @cp-molcell.bsky.social written in collaboration with @tanjamittag.bsky.social , Mikayla Eppert, and Ambuja Navalkar where we review the current evidence for and against the role of density transitions in regulating transcription www.cell.com/molecular-ce...

New preprint from the lab! We identify the ZnF protein Mulberry as a condensation-dependent structural regulator of genome topology that organizes “multi-way regulatory hubs” in early Drosophila embryos.
www.biorxiv.org/content/10.6...

Absolutely! - and all the insights into the usefulness of evolutionary couplings for structure determination, as well.

When certain patterns are implicitly present in large high-quality human data, one should not give too much credit to the machine learning algorithm that mines these data for patterns.

And AlphaFold was only possible because a huge number of experimental structures from which one could generalise was produced and catalogued by scientists over the years (and similarly for protein sequences used for MSAs).

(Because keeping it ontological can also prevent you from excluding any human who doesn't [yet] manifest a given quality in a way we want it to be manifestable, as I tried to argue under the previous post).

A part of it is whether the term is going to be demeaning/insulting. Even then, I can see the force of your objection, but I would still stand by the fact that keeping categories ontological and thus ammenable to being protected by the mimicry objection is a double-edged sword with a positive side.

I, personally, think that something that is more technical and focuses on operation would be better than any already widely used, 'casual' term. People do not object to 'efficient' or 'useful'. Perhaps one can say more than that, but in a similar vein.

This might be interesting:

Me later, 2011-2018. It would be easier to make everyone agree if we (or Turing) took a new term with less ontological and emotional baggage. I think you cannot just decide a term that is widely (and diversely) used to be easily definable.

One last thing I would add. We cannot escape the fact that our knowledge of humans (and perhaps other animals by extension) is largely through introspection. So it is not only the 'opaque' knowledge of how brain works. And we can have reasonable doubts this is extendable to LLMs.

(By the way, it seems we were both at the IMP at some point @giorgio.gilest.ro . Thanks for the discussion!)

My answer is in later posts, where I argue for the need to define this as an ontological capacity that might not be (yet) manifested - as in trainees, which is why they are trainees. Human beings developing in time is very different from a machine that you might want to benchmark at a specific point

I think freezing 'intelligence' as operational/measurable in any other way could be dangerous too, as is, in my view, extending it to machines that, as we know, were actually deliberately designed to mimic manifestation of intelligence without its ontological underpinnings.

... as there in principle rather than only when manifested, knowing that manifestation is contingent on lacks of obstacles and presence of supporting factors etc. The ellusive nature of the definition is a guardrail - just like any attempts to freeze it before ('IQ' etc.) had an effect of excluding.

And the Phillis Wheatley example is, I think, dangerous. Making certain commitments ontological might make them more difficult to extend - but it also prevents using them to exclude. I do think there is a certain robustness (and truth) in acknowledging a shared 'ontological' human capacity...

I think anyone trying using LLMs knows that a little 'push' in the right direction from a human operator at each step makes all the difference in almost any slightly more complex process - I don't think that's an illusion.

My counterargument would be that, perhaps, the moving goal post phenomenon is not dishonesty, but rather trying to name a certain reality that is difficult to put into words but is genuine, and is neither sentience nor consciousness per se, but is indeed about navigating intellectual questions.

Precise control of transcription condensates across S phase balances linker histone expression with DNA replication, ensuring genome stability Marmolejo et al. uncover transcription condensate dynamics at histone locus bodies across the cell cycle. These dynamics are governed by cell cycle (DDK and CDK1/2) and checkpoint (ATR-CHK1) kinases t...

I am excited to share the first paper from the Saldivar lab! A special thank you to all who contributed.

Precise control of transcription condensates across S phase balances linker histone expression with DNA replication, ensuring genome stability: Molecular Cell www.cell.com/molecular-ce...

Filament-driven activation of the Kongming antiviral system by deoxyinosine triphosphate Recently, the Kongming system has been identified as a bacterial anti-phage defense system relied on nucleobase-modified nucleotides for immune signaling. Zhen et al. determine a series of cryo-EM structures of this system, revealing that dITP binding induces filament assembly of KomBC, which elucidats the activation mechanism of the Kongming system.

Online Now: Filament-driven activation of the Kongming antiviral system by deoxyinosine triphosphate Online now:

Check out our new review in Nature Reviews Genetics on de novo emerged genes and proteins. How they emerge, are lost and persist - and how de novo emerged proteins relate to randomized proteins! @bornberglab.bsky.social www.nature.com/articles/s41...

The filamentous ultrastructure of the PopZ condensate is required for its cellular function Nature Structural & Molecular Biology, Published online: 02 February 2026; doi:10.1038/s41594-025-01742-yScholl et al. show that PopZ forms filamentous condensates driven by its helical domain and inhibited by its disordered region. Phase-dependent conformations modulate client interactions and disruption of filamentation or condensation impairs cellular function and growth.

New online: The filamentous ultrastructure of the PopZ condensate is required for its cellular function

DNA-protein cross-links promote cGAS-STING–driven premature aging and embryonic lethality DNA-protein cross-links (DPCs) are highly toxic DNA lesions that block replication and transcription, but their impact on organismal physiology is unclear. We identified a role for the metalloprotease...

Our Science paper is out! 😃

www.science.org/doi/10.1126/...

I was struck, in Sweden, by people having no curteins in their windows. This must have cultural/religious roots, I guess. But it's separate from huge windows.

I do think that using for imitating machines the kind of language that has been traditionally used for humans is dehumanising.

Being a lone young philosopher in such a setting, publishing manifestos read by millions, not peer-reviewed arguments, having a financial conflict of interest, all this cannot be that good for a sober philosophy.

It's not to the credit of a philosophical school that, as soon as a more impressive imitating machine turned up, some fell for it, where what was needed was clarity & regulation. History occasionally tests philosophical schools on moral grounds. And 7 yrs in Sill. Vall. is not that few.

The successes of protein structure prediction are widely known. However, its limitations and failures are less known, especially among non-experts.

Most telling are the failures to predict structure types absent from the training data.
⬜️ This is a distinct machine-learning failure, in ...

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