Erik van Nimwegen

Rapid fluctuations drive complex gene regulation in bacteria Bacteria respond to environmental factors such as antibiotics by inducing regulatory proteins that switch their target genes on or off. Researchers led by Prof. Erik van Nimwegen have discovered that ...

🧪 Gene regulation in bacteria: The team led by @erikvannimwegen.bsky.social discovered that environmental stimuli cause rapid fluctuations in the concentration of regulatory proteins, leading different target genes to respond differently to the same stimulus. www.biozentrum.unibas.ch/news/detail/...

Four panels show different states of the LexA regulon with either high or low concentration of LexA and a target promoter either bound by the LexA repressor, or unbound and active. The figure also indicates the typical rates of transition between these four states. While transitions from bound to unbound always occur at a rate of about 1 per minute, rebinding is very fast when LexA is high (i.e. 1 second) and very slow when LexA is low. Therefore, expression bursts only occur when LexA levels are low. Switches to the low LexA state happen roughly once an hour when DNA damage occurs, but only last on the order of 1 minute because DNA is repaired quickly. Because this is roughly the same rate as the unbinding rate, expression bursts occur stochastically during the short time periods of low LexA levels.

Paper link and graphical abstract:
journals.aps.org/prxlife/abst...

Different Bacterial Genes Have Different Turn-Ons Not all genes respond in the same way to regulation by the same molecule—a property that might enable cells to produce complex genetic responses.

Because of a lack of separation of the time scales for TF binding/unbinding and fluctuations in active TF levels, non-equilibrium gene regulation may be common in bacteria.
Check out this nice piece by ‪@philipcball.bsky.social‬ on our new publication in PRX Life.
physics.aps.org/articles/v18...

PRX Life on X: "Different target genes controlled by the same regulator respond to DNA damage with highly distinct expression responses when fluctuations in transcription factor levels match the timescale of their binding and unbindingfrom DNA. Read the paper: https://t.co/HVwQL3pj1l https://t.co/qVSsqzrTah" / X Different target genes controlled by the same regulator respond to DNA damage with highly distinct expression responses when fluctuations in transcription factor levels match the timescale of their binding and unbindingfrom DNA. Read the paper: https://t.co/HVwQL3pj1l https://t.co/qVSsqzrTah

Levels of active TFs can fluctuate on the same time scale as individual binding and unbinding events to the DNA, causing 'non-equilibrium' gene regulatory responses.
We believe this may be pervasive in bacterial gene regulation.
Check out our new work in PRX Life:
x.com/PRX_Life/sta...

Probabilistic clustering of sequences: Inferring new bacterial regulons by comparative genomics | PNAS Genome-wide comparisons between enteric bacteria yield large sets of conserved putative regulatory sites on a gene-by-gene basis that need to be cl...

Not sure if this is what you mean, but if you want partition any set of sequences into clusters under the assumption that sequences in each cluster derive from a common PSWM, this does so rigorously:
www.pnas.org/doi/10.1073/...

Our paper demonstrating that within-species warfare interactions are ecologically important on human skin is now published in Nature Micro! www.nature.com/articles/s41...

Mostly about the literature I’d say.

No. I don't care if they eventually choose to be a sculptor or a real estate agent. I only expect that if somebody comes to do a PhD with me, that they want to do science and want to learn how to do science, i.e. not demand from me that I should prepare them for how it is going to be in industry.

All valid points Claus. But I'm not concerned about the students. I'm concerned about the science. How it comes under pressure from masses of PhD students that aren't really interested in doing science. Most scarily, the article is arguing that we should adapt 'what a PhD is' to cater to this.

I don't know what to do with questions like this. Obviously some science is done in pharma/biotech. But there are also very strong boundary conditions that will often conflict with 'doing science'. As an academic scientist, we should not adapt our teaching to cater to such boundary conditions.

The majority of La Masia students don't become professional soccer players. Is that an argument to change the education at La Masia to focus more on teaching the skills needed as a gym teacher, sports coach, scout, or sport analyst?

No it isn't. I completely disagree. I'm very happy that the skills acquired during PhD training are also of great value outside academia. Great! But we are in no way shape or form obliged to adapt the PhD to cater to other jobs that students might end up in.

No, academics don't think that at all. Academics merely presume that somebody that chooses to do a PhD wants to learn how to become a scientist. And if they change their mind.. fine.. go do something else.. but don't insist that a PhD education must then also cater to this something else.

Yeah, that's why picked that example ;-)

What industry wants to hire is their business. It is not our job to redefine what a PhD is based on demand. This is terrible logic of the kind: There's too many PhDs in molecular biology and too few plumbers, therefore mol biol professors should teach their PhD students plumbing.

That is not to say that we shouldn't select more stringently. I think there are far too many PhD students. I agree that the balance 'jobs in science'/'PhD students hired' is completely off. But the solution is not redefining a PhD to be something else.

Dont be silly. Does FC Barcelona only take 11 kids in their youth selection? Does music conservatory only take as many piano students as there are new concert pianists per year? I said ambition.

No Torsten. If students do not have the ambition for a career in science, then they should not do a PhD. There are plenty of other educational options.
Can we please stop watering down academic education?

Bonsai: Tree representations for distortion-free visualization and exploratory analysis of single-cell omics data Single-cell omics methods promise to revolutionize our understanding of gene regulatory processes during cell differentiation, but analysis of such data continues to pose a major challenge. Apart from...

Agree. We have been working hard to deal with exactly these problems. Maybe you will find this work helpful:
www.biorxiv.org/content/10.1...

across strains of a bacterial species (which are at similar genomic distances in orthologous regions) so this may be very relevant for us. Thanks

Very interesting. Is it possible to give an intuitive summary of what kind of biases were happening and why the new strategy (which I understand is demanding that reads from both strains map reciprocally to the genomes of species) avoids these biases? We've started doing gene expression comparisons

Is this some sort of Goedel sentence?

Not all persister bacteria are dormant! 🦠

Single-cell imaging of over a million #EColi shows that many antibiotic-resistant persisters were actively growing before drug exposure. Persistence appears to be more dynamic than once thought.
buff.ly/04T4L1k

Diabolus Ex Machina This Is Not An Essay

Amazing account of ChatGPT's sycophancy and confabulation on steroids.

amandaguinzburg.substack.com/p/diabolus-e...

The microbiome of the human facial skin is unique compared to that of other hominids | mSystems Understanding how and why human skin bacteria differ from our closest animal relatives provides crucial insights into human evolution and health. While we have known that human facial skin hosts disti...

Our work on the facial skin microbiome of non-human primates is out in mSystems!

We show there is no close relative of Cutibacterium on the faces of gorillas and chimps at the Lincoln Park Zoo, furthering the mysterious origin of the dominant human skin colonizer.

journals.asm.org/doi/10.1128/...

Truly inmates running the asylum.

One problem we face today is how few people understand the science that helps us all. Some scientists are able to explain the importance of their work. @baym.lol of Harvard University is one of them. Science is for everyone, and benefits us all more than most people know.

Time for a short thread! We developed HiddenFoot, a biophysics-inspired approach to decode single-molecule footprinting data and infer TF, nucleosome, and RNA Pol II binding profiles on individual DNA molecules. One molecule at a time! www.biorxiv.org/content/10.1...

1/6

Great. I think you might find it fun to check what genes are markers of different clades. For example, I checked which genes distinguish the two clades of cells that are annotated as G2M at the top left and bottom left. Below you can see the expression of the top marker (CDK1) on the tree.

But I would suggest you first try Bonsai as is on a dataset that you think has this character, and see what you get.