Lennart Hilbert
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lennarthilbert.bsky.social
Lennart Hilbert
@lennarthilbert.bsky.social
2.4K followers 1K following 490 posts
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
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lennarthilbert.bsky.social
Greetings from the International Zebrafish & Medaka Course (IZMC)

Grüße vom Internationalen Zebrafisch & Medaka Kurs

👋🐟

Photo from teaching this morning for this week’s November German language edition. This FELASA-certificate course is offered via @ezrc.bsky.social at @kit.edu
November 24, 2025 at 12:51 PM
lennarthilbert.bsky.social
Excited to share our new Perspective Article in Advanced Functional Materials:

Integrative Approaches for DNA Sequence-Controlled Functional Materials

We jointly cover scale-bridging simulation, machine learning & experiments from several groups.

advanced.onlinelibrary.wiley.com/doi/10.1002/...
November 22, 2025 at 12:27 PM
lennarthilbert.bsky.social
Almost all hands on deck today in Hilbert lab meeting. Postdoc Ewa very small on Zoom, PhD student Nils substituted for a colleague for a talk; associated fellow Simon and Master student Georg not in the photo. I just felt super happy I can work with this group, so I am sharing selfie greetings 👋 😃
Most of the current Hilbert lab members and Master student interns in the weekly lab meeting.
November 17, 2025 at 9:35 PM
lennarthilbert.bsky.social
Next Tuesday Oct 28, great talks of invited and local speakers of our Synthetic Genomics Center, in Heidelberg and on Zoom!
October 24, 2025 at 1:57 PM
lennarthilbert.bsky.social
Last night Science Slam with a full house at Tollhaus, as part of @kit.edu Science Week. As one of four slammers, our PhD student Mona Wellhäusser @mofrawe.bsky.social entertained a huge audience, putting fish in jello for microscopy, (optically) slicing a pumpkin. Great show, fantastic atmosphere!
October 18, 2025 at 6:58 AM
lennarthilbert.bsky.social
Warming up for October start of KIT teaching by guest lecturing for @unistra.fr Cell Physics Master “Active Droplets”. First of three lectures today. 3:00 h sharp, start to finish 💪

Some travel impressions, including fancy and very white “Le Studium” on Strasbourg Central Campus 🤍

And, Gyoza 🥟
September 26, 2025 at 3:38 PM
lennarthilbert.bsky.social
It was a pleasure and an honor to walk this part of the path together, and amazing to look back at the achievements today. Also, two very smart oral examiners, Alexandra Chambony & Helmut Brandstätter, quite insightful and sharp questions! They’re here, right after the grade was announced.
September 23, 2025 at 9:18 PM
lennarthilbert.bsky.social
What a great doctoral defense by Tim Klingberg @fau.de

Based in the group of our collaborator @vasilyzaburdaev.bsky.social Tim decisively contributed to at least 3 of our own lab’s foundational projects, which he showed today at “Max Planck Zentrum Physik und Medizin”

Some impressions
September 23, 2025 at 9:18 PM
lennarthilbert.bsky.social
If you are at GBM compact "Focus on Condensate Biology", we will be happy to talk to you at our lab's posters:

Mona Wellhäuser, MC15 @mofrawe.bsky.social
Yuzhi Bao, CA03 @yuzhibao.bsky.social
Lennart Hilbert, MC06

Conference abstracts:

gbm-compact.org/abstracts.html

*sketch added as click bait
September 18, 2025 at 11:52 AM
lennarthilbert.bsky.social
Simulation of the formation of a chromatin-attached condensate, which is visited by a gene undergoing transcriptional activation.

Read more about it here:

nyaspubs.onlinelibrary.wiley.com/doi/10.1111/...
September 9, 2025 at 6:40 AM
lennarthilbert.bsky.social
A coarse-grained simulation reproduces, again, the behaviors seen in our synthetic DNA experiments, and explains some effects of finite microscope resolution, as well as complex interactions of condensates and surface DNA strands.
Simulation of surface condensation in the presence of a model polymer chain. (A) Basic interaction rules in a system of diffusing particles result in liquid–liquid phase separation and surface condensation. 2D-projections of simulations show that for a low number of condensate-forming particles, droplets only form on interactive polymer sections. Only at higher numbers of condensate-forming particles can droplets form independently. (B) The association of particles into droplets is detected at lower particle concentrations in the presence of a condensation surface. (C) When increasing the bulk concentration of condensate-forming particles above the pre-wetting concentration, , a dense droplet phase appears in the presence of a condensation surface (top). Without a surface, a dense droplet phase forms only above the higher saturation concentration . Droplet phase concentration obtained using the convex hull around DBSCAN detected clusters. (D) Simulating the limited resolution of a microscope and implementing a quantification of condensate intensities similar to the analysis of microscopy images leads to a progressive increase of intensity above (in the presence of surface, top) or above (without surface, bottom). All values are mean SEM, independent simulations per condition.
September 8, 2025 at 1:50 PM
lennarthilbert.bsky.social
We took a short-cut, designed DNA-nanomotifs behaving similarly to the in vivo liquid phase, condensing in targeted fashion on long, repetitive DNA strands produced bz rolling circle amplification (RCA). Crucial behaviors of the surface condensate regime are reproduced! @xeniatschurikow.bsky.social
Use of synthetic DNA nanostructures to reconstruct the surface condensation process underlying transcription factory formation. (A) The condensed material of a transcription factory is mimicked using X-shaped nanomotifs made of short DNA oligomers. The nanomotifs have sequence-encoded binding sites for other nanomotifs (magenta) and for target areas located on DNA strands (green). These target areas enable the local formation of surface condensates, similar to the condensate formation at genomic control elements. (B) Two-color microscopy images showing nanomotifs (magenta), to which surfaces (green) were added or not added. Images are maximum intensity z-projections, intensity look-up tables were adjusted for each image individually to facilitate visual interpretation. For separate channel images, see Figure S1. (C) Number of condensates per volumetric stack, the nanomotif channel intensity within these condensates, and the nanomotif channel background intensity for increasing nanomotif concentration, in the presence or absence of added condensation surfaces. All values are mean with 95% confidence intervals, 500 bootstrap resamples, volumetric stacks per condition for condensate number and background intensity; for condensate intensity, is the total number of condensates pooled from 20 stacks per condition. For the middle and bottom intensity plots, the circle area is proportional to the number of detected condensates.
September 8, 2025 at 1:50 PM
lennarthilbert.bsky.social
The surface condensation regime holds very specific implications for the behavior of liquid-phase condensates: they are growth-limited by amount of available surface, and localize to these surfaces. The regime occurs at sub-saturated (C<C_sat) concentrations, also relevant for the in vivo regime.
Delineation of the surface condensation regime in contrast to canonical liquid–liquid phase separation (LLPS). Reliable operation of a computing system that uses properties and functions afforded by surface condensation can be expected within the inner regions of the surface condensation regime, above the pre-wetting concentration () and below the saturation concentration (). Blue and red lines in the bottom diagram represent stable concentrations that can be obtained by demixing into condensates via surface condensation or LLPS, respectively. Dashed lines are theoretical expectations and solid lines are expected observations considering a finite microscope resolution. Sketch based on simulations in our previous work.
September 8, 2025 at 1:50 PM
lennarthilbert.bsky.social
The gene-cluster visits can be attributed to liquid-phase mediated adhesion between genes (right side of the box) and condensates formed at super-enhancers (left side). The gene attaches via a liquid bridge, and detaches when losing liquid phase compatibility upon transcriptional activation.
Surface condensation as a process that underlies the formation of transcription factories and subsequent gene-factory visits. (A) Formation of the transcription factory by surface condensation on a regulatory genomic region. RNA polymerase II should be understood to also represent other molecular transcription machinery. (B) A combination of homotypic and surface-directed interactions is required for surface condensation. (C) The gene forms a liquid bridge with the transcription factory and breaks off from the factory after being activated. (D) Capillary forces can compact and zip together chromatin strands.
September 8, 2025 at 1:50 PM
lennarthilbert.bsky.social
The paper points out an intriguing analogy between stem cell-specific gene-cluster visits (see this image) and the von Neumann architecture, underlying (in its essence) the chip design of current electronic computers and computing devices (see above post for a sketch of the analogy).
Transcription factories as hubs of gene control. (A) Microscopic image of RNA polymerase II in the nucleus of a zebrafish embryo, obtained by STEDD super-resolution microscopy, sourced from Ref.38. (B) Sketch of the interaction of a super-enhancer (left) and a gene (right) for the control of transcription via touching of the promoter to the super-enhancer-associated condensate. (C) Sketch of image-based quantification of the distance from a given gene to the nearest polymerase cluster. (D) Algorithm-based sorting of microscopy images into pseudo-time series reconstructs the visit of genes to clusters.6 (E) Sketch of the main stages of the observed association, activation, and detachment of genes.
September 8, 2025 at 1:50 PM
lennarthilbert.bsky.social
"Chromatin-associated condensates as an inspiration for the system architecture of future DNA computers"

Highly conceptual Perspective article, supported by fresh data & simulations from our group. Containing my now 40 years of accumulated "wisdom".

nyaspubs.onlinelibrary.wiley.com/doi/10.1111/...
An analogy between the architectures of electronic computers and transcription factories. (A) Von Neumann computer architecture, in which a CPU is connected to different blocks in a working memory. (B) A transcription factory centrally stores the molecular transcription machinery and can selectively access genes. (C) The operation principle of a CPU-memory architecture based on synthetic DNA nanostructures.
September 8, 2025 at 1:50 PM
lennarthilbert.bsky.social
And here some of the actual electron micrographs, where we mostly see RNA-dense structures, after the chromatin was bleached (as far as I understand the method). With a bit of imagination, you can see the chromatin-decorating RNA transcripts, and also RNA speckles ("granules"). Fascinating!
August 31, 2025 at 3:41 PM
lennarthilbert.bsky.social
And, as I am a great fan of pseudo-time assessment of dynamic processes, here a few snapshots of RNP (ribonucleoprotein) granules transitioning through nuclear pores. So, yes, they even already did pseudo-time :-)
August 31, 2025 at 3:41 PM
lennarthilbert.bsky.social
Fine structural organization of the interphase nucleus in some mammalian cells, Monneron & Bernard, 1969

Gotta love these classic papers about nuclear architecture. In hindsight, all that we understand and discover today was already contained in their images.

www.sciencedirect.com/science/arti...
August 31, 2025 at 3:41 PM
lennarthilbert.bsky.social
Nice paper showing how gene / TSS CpG-hypomethylation can allow long-range regulatory interactions, hypermetyhlation repress these interactions.

"Increased enhancer–promoter interactions during developmental enhancer activation in mammals"

www.nature.com/articles/s41...

@evgenykvon.bsky.social
August 31, 2025 at 1:13 PM
lennarthilbert.bsky.social
Here also cool microscopy assessment of how chromatin compaction (DAPI) in the center and chromatin accessibility (ATAC-seq & H3K9me3 ChIP-seq) at the periphery diverge with progressing differentiation.
August 26, 2025 at 12:06 PM
lennarthilbert.bsky.social
Paused Polymerase II in genome hyper compartmentalization in chicken terminally differentiated adult red blood cells (aRBC), see screenshot.

Excellent paper recommendation from @mariekeoudelaar.bsky.social Thanks!

Andrés Penagos-Puig, ... Mayra Furlan-Magaril

www.nature.com/articles/s41...
August 26, 2025 at 12:06 PM
lennarthilbert.bsky.social
Our first expansion microscopy results. Imaged today on "normal" Zeiss LSM 900, revealing chromatin and RNA polymerase II clusters at an unreal level of detail.

Our PhD student @mofrawe.bsky.social learned the protocol from amazing @mpownall.bsky.social 🙏

Months of preparation are paying off now!
August 14, 2025 at 6:28 PM
lennarthilbert.bsky.social
Role to be filled with best-fitting candidate, 30-day application window. Become part of our vibrant community of research groups at KIT (see photograph), and shape the future of DNA-based synthetic information systems with us! Feel free to reach out with informal enquiries & please spread the word!
July 29, 2025 at 6:24 AM
lennarthilbert.bsky.social
We are hiring! "Researcher in DNA-Based Information Processing Systems" (PhD or postdoc level). Co-supervision by Prof. Ralf Reussner (KIT computer science) and myself (biological systems). Combination of experiments and computational work. Please Apply / Repost!

www.pse.kit.edu/english/karr...
July 29, 2025 at 6:24 AM