Suppressing variation in synthetic circuits

Abstract

Mol Syst Biol. 7: 520 One of the challenges in engineering biological devices is to precisely control the number of parts in each cell. Automobile engineers do not worry about control mechanisms for variation in the number of wheels on a car—if an engineer designs a car with four wheels, then all the cars roll off the assembly line with four wheels. But biology is dynamic, and biological circuits change continuously. Therefore, synthetic biologists are faced with the challenge that the number of DNA, RNA, and protein components of their devices may vary between cells, possibly by several folds. Are there simple methods for ensuring that stoichiometric changes do not affect the proper functioning of the device? In a recent Molecular Systems Biology article, Bleris et al (2011) address this question by identifying useful circuits that can make biological output insensitive to DNA dosage. Although the network of interactions between the components of a cell is dazzlingly complex, biological networks contain smaller, recurrent subnetworks called motifs (Milo et al , 2002). Motifs often convey useful properties, such as altering the response time or magnitude of a propagated signal. A particular motif found in many biological contexts is a three‐node motif called a Type I incoherent feed‐forward loop (I1‐FFL; Figure 1A …