Researchers Achieve Electrochemically Activated Gene Expression

A research team led by experts at Imperial College London have developed a new method that allows gene expression to be precisely altered by supplying electrical signals. The advance could help control biomedical implants in the body or reactions in bioreactors that produce drugs and other useful compounds. Current stimuli used to initiate such reactions are often unable to penetrate materials or pose risk of toxicity.

 “A major issue in synthetic biology is that it is hard to control biological systems in the way we control artificial ones,” says coauthor Joshua Lawrence with the Department of Biochemistry at University of Cambridge. “If we want to get a cell to produce a specific chemical at a certain time we can’t just change a setting on a computer—we have to add a chemical or change the light conditions. The tools we’ve created as part of this project will enable researchers to control the gene expression and behavior of cells with electrical signals instead without any loss in performance.”

Gene expression is the process by which genes are activated to produce new molecules and other downstream effects in cells. In organisms, it is regulated by regions of the DNA called promoters. Some promoters, called inducible promoters, can respond to different stimuli, such as light, chemicals and temperature. Electrogenetic systems have already been explored as a means to control gene expression, but so far have lacked precision. The newly proposed system, described in a recent issue of Science Advances, allows accuracy to be obtained for the first time using electrical stimulus in bacteria.

The research team redesigned the PsoxS promoter to respond more strongly to electrical stimuli provided by the delivery of electrons. The responses included both activation and repression of gene expression. To prove their concept, they then took a protein from jellyfish that produces a glow and used the new promoter and electrons to induce its expression in bacteria—making the cells glow only when the system was “on.” In a different configuration of the system, researchers created a bacteria that was glowing when the system was “off” and stopped glowing when the system was “on.”

Dr. Rodrigo Ledesma Amaro, lecturer at Imperial College London and leader of the RLAlab research group said the project originated as a blue sky idea during a synthetic biology student competition. “Thanks to strong dedication, years of work and a great team effort, that initial idea was turned into a reality and we now have a variety of new technologies to use electricity to control the fate of cells,” Dr. Amaro adds.

The team is now planning on developing different promoters that will act to induce different downstream factors so that simultaneous electrical signals can express different genes, independent of one another. Building a larger library of promoters and downstream factors means the current system can be adapted for use in yeast, plants and animals, the team adds.