Scientists engineer new tools to electronically control gene expression
Date:
May 4, 2022
Source:
Imperial College London
Summary:
Researchers have created an improved method for turning genes on
and off using electrical signals.
FULL STORY ========================================================================== Researchers have created an improved method for turning genes on and
off using electrical signals.
========================================================================== Researchers, led by experts at Imperial College London, have developed
a new method that allows gene expression to be precisely altered 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 risk of toxicity -- electricity holds the solution.
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.
Using electricity to control gene expression has opened a new field of
research and while such electrogenetic systems have been previously
identified they have lacked precision during the presence or absence
of electrical signals, limiting their applications. The newly proposed
system, with engineered promoters, allows such accuracy to be obtained
for the first time using electrical stimulus in bacteria.
The research is published today in Science Advances.
========================================================================== Co-lead author Joshua Lawrence said: "A major issue in synthetic biology
is that it is hard to control biological systems in the way we control artificial ones. 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 behaviour of cells with electrical
signals instead without any loss in performance.
"We hope that by further developing these tools we really will be able to control biological systems with a flick of a switch." In this research,
the PsoxS promoter was redesigned to respond more strongly to electrical stimuli, provided by the delivery of electrons. The newly engineered
PsoxS promoters were able not only to activate gene expression but also
repress it.
Electrically stimulated gene expression has so far been difficult
to conduct in the presence of oxygen, limiting its use in real-life applications. The new method is viable in the presence of oxygen,
meaning it can be replicated across different species of bacteria
and used in applications such as medical implants and bioindustrial
processes. Electrochemical tools can be adjusted for different tasks by
tuning them to a specific level, via change in electrode potential.
========================================================================== Biomedical implants often use a stimuli to produce a certain drug or
hormone in the body. Not all stimuli are suitable; light is unable
to penetrate the human body and chemical ingestion can lead to
toxicity. Electric stimuli can be administered via electrodes, giving
direct and safe delivery.
For large bioreactors (sometimes the size of a building), that produce chemicals, drugs or fuels, the large volume of culture can be difficult
to penetrate with light and expensive to feed with chemical inducers,
so delivery of electrons provides a solution.
For their proof-of-concept study, the researchers took the 'glowing'
protein from jellyfish, 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."
The team are 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.
Dr Ledesma-Amaro, from the Department of Bioengineering at Imperial,
supervised the research that was carried out by Joshua Lawrence, currently
at the University of Cambridge and Yutong Yin, currently at the University
of Oxford.
The research is the result of a larger collaborations of experts
from across Imperial's Departments of Chemistry, Life Sciences and Bioengineering, the Imperial College Translation & Innovation Hub,
Cambridge University and the University of Milan.
========================================================================== Story Source: Materials provided by Imperial_College_London. Original
written by Ayesha Khan.
Note: Content may be edited for style and length.
========================================================================== Journal Reference:
1. Joshua M. Lawrence, Yutong Yin, Paolo Bombelli, Alberto Scarampi,
Marko
Storch, Laura T. Wey, Alicia Climent-Catala, Geoff S. Baldwin, Danny
O'Hare, Christopher J. Howe, Jenny Z. Zhang, Thomas E. Ouldridge,
Rodrigo Ledesma-Amaro. Synthetic biology and bioelectrochemical
tools for electrogenetic system engineering. Science Advances,
2022; 8 (18) DOI: 10.1126/sciadv.abm5091 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/05/220504144527.htm
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