The mystery of turning genes on and off

When it comes to biological engineering systems, bioengineers need to strictly control the expression of an inducible gene. In such cases, leaky protein production must be avoided but without affecting the achievable range of expression.

To make this possible, bioengineers need to control when specific sets of genes are turned on and off to allow careful regulation of the biochemical processes involved.

Turning the genes on and off feels simple, but performing it on a living cell is a challenge. Every cell is slightly different, and the processes involved are not 100 percent reliable.

To address this problem, scientists from the University of Bristol were inspired by nature, where several processes control the emergency process at the same time.

In their study, scientists have shown how to use multiple types of controls simultaneously in living cells by making sure it does not develop exactly when needed.

They simultaneously controlled transcription and translation and showed how basal expression could reduce an educational system, with little effect on the highest level of emotion. Using this approach, they created several tight-feeling systems exhibiting a number of changes in their output after entry.

They have also shown how multi-level control can suppress transcription noise and create digital-like switches between ‘on’ and ‘off’ states.

The team showed that using this type of multilevel control could be some of the most high-performance mutations for gene expression built to date.

Professor Claire Grierson, co-author and Head of the Bristol School of Biological Sciences, said: “What was amazing about this project was how well it worked to make use of two of the key life-threatening processes present in every cell – transcription and translation. ”

Dr Thomas Gorochowski, senior author and Research Fellow of the University of the Royal Society of Bristol, said: “When we invent microbes, we often try to simplify our systems, thinking we have better control over what happens. But what we have shown is that incorporating some biological complexities may be the best way to unleash the potential for tomorrow’s high-tech biotechnologies. ”

Magazine Information:
  1. Greco, FV, Pandi, A., Erb, TJ, et al. Tuning the dogma in the middle for tight multi-level control of gene expression. Nat Commun 12, 1738 (2021). DOI: 10.1038 / s41467-021-21995-7