Qualitative modeling, analysis, and control of synthetic regulatory circuits

International audienceQualitative modeling approaches are promising and still underexploited tools for the analysis and design of synthetic circuits. They can make predictions of circuit behavior in the absence of precise, quantitative information. Moreover, they provide direct insight into the relation between the feedback structure and the dynamical properties of a network. We review qualitative modeling approaches by focusing on two specific formalisms, Boolean networks and piecewise-linear differential equations, and illustrate their application by means of three well-known synthetic circuits. We describe various methods for the analysis of state transition graphs, discrete representations of the network dynamics that are generated in both modeling frameworks. We also briefly present the problem of controlling synthetic circuits, an emerging topic that could profit from the capacity of qualitative modeling approaches to rapidly scan a space of design alternatives

Predictive biology: modelling, understanding and harnessing microbial complexity

Predictive biology is the next great chapter in synthetic and systems biology, particularly for microorganisms. Tasks that once seemed infeasible are increasingly being realized such as designing and implementing intricate synthetic gene circuits that perform complex sensing and actuation functions, and assembling multi-species bacterial communities with specific, predefined compositions. These achievements have been made possible by the integration of diverse expertise across biology, physics and engineering, resulting in an emerging, quantitative understanding of biological design. As ever-expanding multi-omic data sets become available, their potential utility in transforming theory into practice remains firmly rooted in the underlying quantitative principles that govern biological systems. In this Review, we discuss key areas of predictive biology that are of growing interest to microbiology, the challenges associated with the innate complexity of microorganisms and the value of quantitative methods in making microbiology more predictable.Defence Threat Reduction Agency (Grant HDTRA1-15-1-0051