scholarly journals Generating Synthetic Gene Regulatory Networks

2008 ◽  
pp. 237-249 ◽  
Author(s):  
Ramesh Ram ◽  
Madhu Chetty
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Synthetic Gene ◽  
Gene Regulatory

scholarly journals Synthetic gene-regulatory networks in the opportunistic human pathogenStreptococcus pneumoniae

2020 ◽  
Vol 117 (44) ◽  
pp. 27608-27619 ◽  
Author(s):  
Robin A. Sorg ◽  
Clement Gallay ◽  
Laurye Van Maele ◽  
Jean-Claude Sirard ◽  
Jan-Willem Veening
Keyword(s):  
Gene Expression ◽  
Virulence Factor ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Combinatorial Libraries ◽  
Regulatory Elements ◽  
Synthetic Gene ◽  
Expression Control ◽  
Gene Expression Control ◽  
Gene Regulatory

Streptococcus pneumoniaecan cause disease in various human tissues and organs, including the ear, the brain, the blood, and the lung, and thus in highly diverse and dynamic environments. It is challenging to study how pneumococci control virulence factor expression, because cues of natural environments and the presence of an immune system are difficult to simulate in vitro. Here, we apply synthetic biology methods to reverse-engineer gene expression control inS. pneumoniae. A selection platform is described that allows for straightforward identification of transcriptional regulatory elements out of combinatorial libraries. We present TetR- and LacI-regulated promoters that show expression ranges of four orders of magnitude. Based on these promoters, regulatory networks of higher complexity are assembled, such as logic AND gates and IMPLY gates. We demonstrate single-copy genome-integrated toggle switches that give rise to bimodal population distributions. The tools described here can be used to mimic complex expression patterns, such as the ones found for pneumococcal virulence factors. Indeed, we were able to rewire gene expression of the capsule operon, the main pneumococcal virulence factor, to be externally inducible (YES gate) or to act as an IMPLY gate (only expressed in absence of inducer). Importantly, we demonstrate that these synthetic gene-regulatory networks are functional in an influenza A virus superinfection murine model of pneumonia, paving the way for in vivo investigations of the importance of gene expression control on the pathogenicity ofS. pneumoniae.

scholarly journals Spatial-Stochastic modelling of synthetic gene regulatory networks

2019 ◽  
Vol 468 ◽  
pp. 27-44
Author(s):  
Cicely K. Macnamara ◽  
Elaine I. Mitchell ◽  
Mark A.J. Chaplain
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Stochastic Modelling ◽  
Synthetic Gene ◽  
Gene Regulatory
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