MSGID: 1:317/3 62735333   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    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   
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   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.   
      
      
      
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   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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