The most profound insights are often also the most simple:
growth-rate, by setting the dilution rate of intra-cellular molecules, controls the sensitivity of gene regulatory circuits. In retrospect it seems crazy that this effect seems to have been overlooked so far.
https://www.science.org/doi/10.1126/sciadv.adu9279
growth-rate, by setting the dilution rate of intra-cellular molecules, controls the sensitivity of gene regulatory circuits. In retrospect it seems crazy that this effect seems to have been overlooked so far.
https://www.science.org/doi/10.1126/sciadv.adu9279
Comments
The O'Shea lab later confirmed a critical influence of growth rates in experiments: http://dx.doi.org/10.1126/science.1230996
But I think if you make an insinuation like this it is up to you to provide a reference for exactly what it is 'people like Jonathan Warner' thought of.
and they are strongly growth rate regulated
so maybe they thought of this new idea
I think, but of course can't find an
Either there is a concrete reference so we can judge whether it was...or there isn't.
of course the Khorana lab and PCR is the well known counter, but that is one example
Since many molecules, including those involved in signaling and gene regulation, are stable relative to the doubling time of the cell, their intra-cellular dilution rate is set by the growth-rate and simple theoretical
for the behavior of gene regulatory circuitry.
For example, through the coupling to growth-rate, a simple positive feedback loop, i.e. an auto-activating operon, becomes a regulatory switch that switches from uninduced at high growth-rate to
often dramatically. In general, the theory predicts that fast growing cells effectively ‘mute’ external signals when growing fast, and become highly sensitive to alternative nutrients or stresses when growth is slow or arrested.
We tested this
using the 'hydrogen atom of gene regulation': the lac operon of E. coli. We predict that the critical inducer concentration to induce the lac operon should decrease quadratically with doubling time.
And indeed it does! Simple batch culture
I find it almost astonishing
https://www.biorxiv.org/content/10.1101/2025.02.10.637566v3.abstract