lennarthilbert.bsky.social
Studying the cell nucleus in search of inspiration for future DNA computers. Systems Biology professor at Karlsruhe Institute of Technology, post opinions mine alone.
hilbertlab.org
366 posts
2,286 followers
906 following
Getting Started
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❤️
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We’ll advertise (hopefully soon) a quite explorative postdoc position. Might be outside your area, but you can keep an eye out :-)
Good luck 🍀 🤞
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Does German-speaking Germany also hold relevance?
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The DNA strands A and B were prepared in the same reaction, they are initially mixed. It is only upon addition of the two selectively associating and mutually repelling liquids A and B that they sort apart.
Sorry for channel crosstalk from liquid B to A (blue to magenta), sorry. Working on it :-)
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It is still not entirely safe to say the F word in public ;-)
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Broke the thread again 🤦♂️
bsky.app/profile/lenn...
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OK, gotta stop for today, it’s bed time. Let’s see when Incan come back to this great review paper 😃
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I might have to go back to thus classic. I missed the variability in Pol II-Mediator overlap!
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I am dying, our weird-a## zebrafish “let’s call Pol II clusters pastry items based on shape”-paper is cited in the same section as Eskiw et al. That paper to me is such a huge part of where our field originated, and it’s such a good paper! ☺️
I should read Castells-Garcia, not sure how I missed that
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Wasn’t there also actin? I worked on myosin-actin during my PhD, so I found this soooo confusing 😅
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Right. It’s kind of an obvious regulatory solution. No qualms with it.
But why do some people come and ask “oh, but what about regulatory specificity, huh? HUH???” Like it’s some hyper-intellectual gotcha, while the answer is, sorry, obvious :-/
(I’m intentionally trying to add some drama.)
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I wasn’t aware of this. How cool!
However, Ser5P and also generic Pol II clusters of this size (few complexes, count of tens or less) are likely short-lived, so the travel time to such a cluster might not be so functionally relevant?!
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I wasn’t aware of this. How cool!
However, Ser5P and also generic Pol II clusters of this size (few complexes, count of tens or less) are likely short-lived, so the travel time to such a cluster might not be so functionally relevant?!
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Box 1 is great, especially helpful to give these mini summaries separately from text for newcomers.
Box 2 is well done, fully correct. But I’ll skip it because it channels the year long, embarrassing, traumatizing discussions “is it really really phase separation, or does it only look like LLPS?” 😵💫
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I’d say that distinction hits the nail on the head. Thanks for that much-needed simplicity!
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So, what’s the difference between a transcription factory and a transcriptional condensate? If you’re only *transcriptional*, apparently, you lack a permanently associated gene? ;-)
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Interesting. All regulatory elements are depicted *on the surface* of the factory. It fits our data, existing published record, and also the 1990s papers.
Only problem: I didn’t get it for about two years, and-wasted two years of our lab chasing placement of genes *inside* factories. Oh well… 🤦♂️
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💗
Biologists who consider different views and terminology are valid? I thought spitting venom and trash-talking our colleagues online was the only acceptable way to settle this stuff?!?
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Sorry broke the thread…
bsky.app/profile/lenn...
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Very much agree. A picture where the factory is “liquid” can explain local concentration with a lack of consistent extractability. A new concept was needed to reconcile factories with dynamic structure, and intracellular liquid condensates offer that combination.
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These were the real OG studies. If you take the time to understand the techniques, pictures, and 40-years dated language: they already contain almost everything. Only our light microscopes and molecular techniques improved.
But I thought criticism was non-extractability of factories 🧐
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“we contrast historical work on transcription factories with recent findings on transcriptional condensates to better understand the architecture and functional
relevance of transcription compartments.” So reassuring. I wrote similar stuff, but was never 100% sure of “factories->condensates”. Phew!
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😅
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Excellent! This makes complete sense, once you put these different elements together, this outcome is only logical. Thanks for pointing to the Ext Data Fig 4, I did not go into the SI on first reading.
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Did you make this sketch now? It's great, I would very much agree with this scenario and explanation overall! For anyone not convinced yet, the might HP1-BRD4 construct might, indeed, be the best evidence to argue your point.
In the case of heterochromatin, is bulk chromatin also excluded?
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Only checked out the figures thus far, but already a looks great!
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I hope (and believe) there’s plenty left to discover and understand, still have quite a few years to fill till retirement 😅
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Already looking forward to reading with more time, just skimmed the figures for now. Not sure who else would be more well-positioned to debate this topic: you know the old factory as well as the new condensates community very well.
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*comes, probably thinking of ice cream too much 🍦
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Yeah that’s not meta stable. Meta stable cones, for me, cones from dynamical systems theory, and means: it’s a fixed point, probably even a stable one, but with a small basin of attraction, and there’s another stable fixed point with much larger basin of attraction. (And maybe energetically lower.)
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Equilibrium, at the microscopic scale, is a statistical property. A distribution into different states. In my understanding, at least.
So, speaking of one structure as *the* equilibrium structure is maybe why it is hard to answer that question?
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I have seen what you’re capable of :-p
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How can I motivate you to keep posting?
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Fantastic manuscript, had to read through it immediately!
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Is the lower / higher chromatin density after phase separation for euchromatin / heterochromatin also explicable by sparser / denser placement of the affinity polymer blocks in the respective regions? Maybe the attached sketch can explain what I mean :-)
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What is the reason for the non-wetting condensate size increase in absence of wetting condensates? Is it that specifically small wetting condensates stiffen the chromatin meshwork, thus exerting a stronger mechanical frustration of the non-wetting condensate formation?
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Thank you so much for preprinting! This is a real Brangwynne lab work, theory & experiment & clear logic. It can be used practically directly as teaching material for an advanced phase sep class (as I do). I'll post with some questions...
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Also need to appreciate the nod to chromatin-associated condensates as a mechanism with an ability for exceptionally rapid chromatin reorganization and, potentially, transcription control.
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The phase diagram is great. We can see how condensate liquid material and chromatin strands interact in a variety of nevertheless systematic outcomes.
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Amazing photographs, one can see the excitement on everyone's faces ❤️
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@sfuscience.bsky.social in Vancouver seeks world-leading applicants in strategic areas that include Biophysics (featuring an internationally recognized and highly collaborative group of researchers centered in @sfuphysics.bsky.social).