PT  - JOURNAL ARTICLE
AU  - John P. Marken
AU  - Fangzhou Xiao
AU  - Richard M. Murray
TI  - A geometric and structural approach to the analysis and design of biological circuit dynamics: a theory tailored for synthetic biology
AID  - 10.1101/2020.02.18.953620
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.02.18.953620
4099  - http://biorxiv.org/content/early/2020/02/19/2020.02.18.953620.short
4100  - http://biorxiv.org/content/early/2020/02/19/2020.02.18.953620.full
AB  - Much of the progress in developing our ability to successfully design genetic circuits with predictable dynamics has followed the strategy of molding biological systems to fit into conceptual frameworks used in other disciplines, most notably the engineering sciences. Because biological systems have fundamental differences from systems in these other disciplines, this approach is challenging and the insights obtained from such analyses are often not framed in a biologically-intuitive way. Here, we present a new theoretical framework for analyzing the dynamics of genetic circuits that is tailored towards the unique properties associated with biological systems and experiments. Our framework approximates a complex circuit as a set of simpler circuits, which the system can transition between by saturating its various internal components. These approximations are connected to the intrinsic structure of the system, so this representation allows the analysis of dynamics which emerge solely from the system’s structure. Using our framework, we analyze the presence of structural bistability in a leaky autoactivation motif and the presence of structural oscillations in the Repressilator.