Abstract:
:Gene expression circuitries, which enable cells to detect precise levels within a morphogen concentration gradient, have a pivotal impact on biological processes such as embryonic pattern formation, paracrine and autocrine signalling, and cellular migration. We present the rational synthesis of a synthetic genetic circuit exhibiting band-pass detection characteristics. The components, involving multiply linked mammalian trans-activator and -repressor control systems, were selected and fine-tuned to enable the detection of 'low-threshold' morphogen (tetracycline) concentrations, in which target gene expression was triggered, and a 'high-threshold' concentration, in which expression was muted. In silico predictions and supporting experimental findings indicated that the key criterion for functional band-pass detection was the matching of componentry that enabled sufficient separation of the low and high threshold points. Using the circuitry together with a fluorescence-encoded target gene, mammalian cells were genetically engineered to be capable of forming a band-like pattern of differentiation in response to a tetracycline chemical gradient. Synthetic gene networks designed to emulate naturally occurring gene behaviours provide not only insight into biological processes, but may also foster progress in future tissue engineering, gene therapy and biosensing applications.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Greber D,Fussenegger Mdoi
10.1093/nar/gkq671subject
Has Abstractpub_date
2010-10-01 00:00:00pages
e174issue
18eissn
0305-1048issn
1362-4962pii
gkq671journal_volume
38pub_type
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