Bioengineers learn the secrets of precisely turning genes on and off

In a recent study led by the University of Bristol, scientists demonstrated how they can simultaneously use multiple forms of regulation in living cells to tightly control gene expression and open new avenues for improved biotechnologies.

Developed microbes are increasingly being used to enable the sustainable and clean production of chemicals, medicines and much more. 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.

Their findings are reported today in the journal Nature Communications

Veronica Greco, lead author and a Royal Society-funded Ph.D. student at the School of Biological Sciences in Bristol, said: “While turning a gene on or off sounds simple, getting a living cell to do it on command is a real challenge. the processes involved are not 100 percent reliable. “

To solve this problem, the team took inspiration from nature, where important events are often managed by multiple processes at the same time.

Veronica Greco added, “If you look at a Venus flycatcher, you can see that a trap only closes when multiple hairs are triggered at the same time. This helps reduce the chance of a trap accidentally closing. We wanted to do something similar in controlling it. of the expression of a gene in a cell, which adds multiple levels of regulation to ensure that it is only activated when we want it to. “

Professor Claire Grierson, co-author and head of the School of Biological Sciences in Bristol, added: “What was great about this project was how well it worked to harness two of the core processes present in each cell and the whole life support – transcription and translation. “

The team showed that using this kind of multi-level regulation, they were able to create some of the best performing gene expression switches to date.

Additionally, in collaboration with Dr. Amir Pandi and Prof Tobias Erb from the Max Planck Institute for Terrestrial Microbiology in Bristol, take it one step further. They showed that even when used outside of living cells, these multi-level systems afforded some of the strictest controls over gene expression to date.

Dr. Thomas Gorochowski, senior author and a Royal Society University Research Fellow in Bristol, said: “When we develop microbes, we often try to simplify our systems as much as possible because we think we have more control over what happens. has shown that embracing some of the inherent complexities of biology could be key to unlocking its full potential for tomorrow’s high-precision biotechnologies. ”