Abstract:
:A common approach to design genetic circuits is to compose gene expression cassettes together. While appealing, this modular approach is challenged by the fact that expression of each gene depends on the availability of transcriptional/translational resources, which is in turn determined by the presence of other genes in the circuit. This raises the question of how competition for resources by different genes affects a circuit's behavior. Here, we create a library of genetic activation cascades in E. coli bacteria, where we explicitly tune the resource demand by each gene. We develop a general Hill-function-based model that incorporates resource competition effects through resource demand coefficients. These coefficients lead to nonregulatory interactions among genes that reshape the circuit's behavior. For the activation cascade, such interactions result in surprising biphasic or monotonically decreasing responses. Finally, we use resource demand coefficients to guide the choice of ribosome binding site and DNA copy number to restore the cascade's intended monotonically increasing response. Our results demonstrate how unintended circuit's behavior arises from resource competition and provide a model-guided methodology to minimize the resulting effects.
journal_name
ACS Synth Bioljournal_title
ACS synthetic biologyauthors
Qian Y,Huang HH,Jiménez JI,Del Vecchio Ddoi
10.1021/acssynbio.6b00361subject
Has Abstractpub_date
2017-07-21 00:00:00pages
1263-1272issue
7issn
2161-5063pii
10.1021/acssynbio.6b00361journal_volume
6pub_type
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