Combinatorial Synthesis of Genetic Networks
C
lin C. Guet,13
Michael B. Elowitz,3
Weihong Hsing,1
Stanislas Leibler123*
A central problem in biology is determining how genes interact as
parts of functional networks. Creation and analysis of synthetic networks, composed of well-characterized genetic elements, provide a
framework for theoretical modeling. Here, with the use of a combinatorial method, a library of networks with varying connectivity was generated in Escherichia coli. These networks were
composed of genes encoding the transcriptional regulators LacI, TetR,
and lambda CI, as well as the corresponding promoters. They displayed phenotypic behaviors resembling binary logical circuits, with two
chemical "inputs" and a fluorescent protein "output." Within this simple system, diverse computational functions arose through changes in network connectivity. Combinatorial synthesis provides an
alternative approach for studying biological networks, as well as an
efficient method for producing diverse phenotypes in vivo.
1 Howard Hughes Medical Institute, Department
of Molecular Biology,
2 Department of Physics,
Princeton University, Princeton, NJ 08544, USA.
3 The Rockefeller University, 1230 York Avenue, New
York, NY 10021, USA.
*
To whom correspondence should be addressed. Laboratory for
Living Matter, The Rockefeller University, 1230 York Avenue, New York,
NY 10021, USA.