A synthetic oscillatory network of transcriptional regulators.
Networks of interacting biomolecules carry out many essential functions in living cells, but the 'design principles' underlying the functioning of such intracellular networks remain poorly understood, despite intensive efforts including quantitative analysis of relatively simple systems. Here we present a complementary approach to this problem: the design and construction of a synthetic network to implement a particular function. We used three transcriptional repressor systems that are not part of any natural biological clock to build an oscillating network, termed the repressilator, in Escherichia coli. The network periodically induces the synthesis of green fluorescent protein as a readout of its state in individual cells. The resulting oscillations, with typical periods of hours, are slower than the cell-division cycle, so the state of the oscillator has to be transmitted from generation to generation. This artificial clock displays noisy behaviour, possibly because of stochastic fluctuations of its components. Such 'rational network design may lead both to the engineering of new cellular behaviours and to an improved understanding of naturally occurring networks.
Elowitz
M B
MB
Department of Molecular Biology and Physics, Princeton University, New Jersey 08544, USA. melowitz@princeton.edu
Leibler
S
S
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001683:Biological Clocks; D004268:DNA-Binding Proteins; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins; D005583:Fourier Analysis; D005798:Genes, Bacterial; D049452:Green Fluorescent Proteins; D056968:Lac Repressors; D008164:Luminescent Proteins / Q000096:biosynthesis; D008957:Models, Genetic; D010957:Plasmids; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D013269:Stochastic Processes; D014158:Transcription, Genetic; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D056968:Lac Repressors; C539064:LacI protein, E coli; D008164:Luminescent Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins; C034811:tetracycline resistance-encoding transposon repressor protein; D049452:Green Fluorescent Proteins