ABSTRACT

Biological systems often function reliably in diverse environments despite internal or external perturba-

tions. This behavior is often characterized as ‘‘robustness.’’ Based on extensive studies over the last

several decades, much of this robustness can be attributed to the control of gene expression through

complex cellular networks [1-4]. These networks are known to consist of various regulatory modules,

including feedback [5] and feed-forward [6] regulation and cell-cell communication [7]. With these

basic regulatory modules and motifs, researchers are now constructing artificial networks that mimic

nature to gain fundamental biological insight and understanding [8]. In addition, other artificial net-

works that are engineered with novel functions will serve as building blocks for future practical appli-

cations. These efforts form the foundation of the recent emergence of synthetic biology [3,9,10]. These

artificial networks are interchangeably called ‘‘synthetic gene circuits’’ or ‘‘engineered gene circuits.’’

Recent accomplishments in synthetic biology include engineered switches [11-14], oscillators [15,16],

logic gates [17-19], metabolic control [20], reengineered translational machinery [21], population control

[22] and pattern formation [23] using natural or synthetic [24] cell-cell communication, reengineered

viral genome [25], and hierarchically complex circuits built upon smaller, well-characterized

functional modules [26]. In addition to programming cellular dynamics, efforts have also been made

toward the construction of in vitro gene circuits using cell extracts [27,28].