Researchers have created an improved method for turning genes on and off using electrical signals.
Researchers, led by experts from Imperial College London, have developed a new method that can precisely alter gene expression by supplying and removing electrons.
This could help control biomedical implants in the body or reactions in large “bioreactors” that produce drugs and other useful compounds. Current stimuli used to initiate such reactions are often unable to penetrate materials or pose a risk of toxicity – electricity holds the solution.
Gene expression is the process by which genes are “turned on” to produce new molecules and other effects downstream in cells. In organisms, it is regulated by regions of DNA called promoters. Some promoters, called inducible promoters, can respond to different stimuli, such as light, chemicals, and temperature.
The use of electricity to control gene expression opened a new field of research and although such electrogenetic systems had already been identified, they lacked precision in the presence or absence of electrical signals, limiting their apps. The newly proposed system, with engineered promoters, achieves such precision for the first time using an electrical stimulus in bacteria.
The research is published today in Scientists progress.
Co-lead author Joshua Lawrence said: “A major problem in synthetic biology is that it is difficult to control biological systems in the same way that we control artificial systems. If we want a cell to produce a chemical specific at a certain time, we can’t just change a setting on a computer, we have to add a chemical or change the lighting conditions.
“The tools we have created in this project will allow researchers to control gene expression and cell behavior with electrical signals instead without any loss in performance.
“We hope that by further developing these tools, we will truly be able to control biological systems at the flick of a switch.”
In this research, the PsoxThe S promoter has been redesigned to respond more strongly to electrical stimuli, delivered by electron delivery. The new PsoxS promoters were able not only to activate gene expression but also to repress it.
Electrically stimulated gene expression has so far been difficult to achieve in the presence of oxygen, which limits its use in real-world applications. The new method is viable in the presence of oxygen, meaning it can be replicated on different species of bacteria and used in applications such as medical implants and bioindustrial processes. Electrochemical tools can be adjusted for different tasks by setting them to a specific level, via a change in electrode potential.
Biomedical implants often use a stimulus to produce a certain drug or hormone in the body. Not all stimuli are suitable; light is unable to penetrate the human body, and ingestion of chemicals can lead to toxicity. Electrical stimuli can be administered via electrodes, giving direct and safe delivery.
For large (sometimes building-sized) bioreactors, which produce chemicals, drugs, or fuels, the large culture volume can be difficult to penetrate with light and expensive to power with chemical inducers, therefore electron delivery provides a solution.
For their proof-of-concept study, the researchers took the “glowing” jellyfish protein and used the new promoter and electrons to induce its expression in bacteria, causing cells to glow only when the system was “on.” In a different configuration of the system, the researchers created a bacterium that glowed when the system was “off” and stopped glowing when the system was “on.”
The project was born from an idea for blue skies during a synthetic biology student competition. Through strong dedication, years of hard work and a great team effort, that initial idea became a reality and we now have a variety of new technologies for using electricity to control the fate of cells.”
Dr Rodrigo Ledesma Amaro, Lecturer at Imperial College London and head of the RLAlab research group
The team now plans to develop different promoters that will act to induce different downstream factors, so that simultaneous electrical signals can express different genes, independently of each other. Building a larger library of promoters and downstream factors means that the current system can be adapted for use in yeast, plants and animals.
Dr Ledesma-Amaro, from Imperial’s Department of Bioengineering, supervised research by Joshua Lawrence, now at Cambridge University, and Yutong Yin, now at Oxford University. The research is the result of a wider collaboration of experts from Imperial’s Chemistry, Life Sciences and Bioengineering Departments, Imperial College Translation & Innovation Hub, University of Cambridge and the University of Milan.
Lawrence, J.M. et al. (2022) Synthetic Biology and Bioelectrochemical Tools for Electrogenetic Systems Engineering. Scientific advances. doi.org/10.1126/sciadv.abm5091.