title: A molecular noise generator.
abstract: Recent studies have demonstrated that intracellular variations in the rate of gene expression are of fundamental importance to cellular function and development. While such 'noise' is often considered detrimental in the context of perturbing genetic systems, it can be beneficial in processes such as species diversification and facilitation of evolution. A major difficulty in exploring such effects is that the magnitude and spectral properties of the induced variations arise from some intrinsic cellular process that is difficult to manipulate. Here, we present two designs of a molecular noise generator that allow for the flexible modulation of the noise profile of a target gene. The first design uses a dual-signal mechanism that enables independent tuning of the mean and variability of an output protein. This is achieved through the combinatorial control of two signals that regulate transcription and translation separately. We then extend the design to allow for DNA copy-number regulation, which leads to a wider tuning spectrum for the output molecule. To gain a deeper understanding of the circuit's functionality in a realistic environment, we introduce variability in the input signals in order to ascertain the degree of noise induced by the control process itself. We conclude by illustrating potential applications of the noise generator, demonstrating how it could be used to ascertain the robust or fragile properties of a genetic circuit.
authors.affiliation: Department of Electrical Engineering, Princeton University, J-319 E-quad, Princeton, NJ 08544-5263, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Lu
authors.forename: Michael
authors.initials: M
authors.lastname: Ferry
authors.forename: Ron
authors.initials: R
authors.lastname: Weiss
authors.forename: Jeff
authors.initials: J
authors.lastname: Hasty
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D008957:Models, Genetic; D014176:Protein Biosynthesis / Q000235:genetics / Q000502:physiology; D015202:Protein Engineering / Q000379:methods*; D012333:RNA, Messenger / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013269:Stochastic Processes
chemical_list: D012333:RNA, Messenger; D004247:DNA