An engineering design approach to systems biology

Abstract

Measuring and modeling the integrated behavior of biomolecular-cellular networks is central to systems biology. Over several decades, systems biology has been shaped by quantitative biologists, physicists, mathematicians, and engineers in different ways. However, the basic and applied versions of systems biology are not typically distinguished, which blurs the separate aspirations of the field and its potential for real-world impact. Here, we articulate an engineering approach to systems biology, which applies educational philosophy, engineering design, and predictive models to solve contemporary problems in an age of biomedical Big Data. A concerted effort to train systems bioengineers will provide a versatile workforce capable of tackling the diverse challenges faced by the biotechnological and pharmaceutical sectors in a modern, information-dense economy.

Fig. 1

Workflows for systems biology and systems bioengineering. (A) The scientific method applied to systems biology. (B) Engineering design approach applied to systems bioengineering. The gray text provides example case studies^, selected from Arkin and Schaffer, 2011.

Fig. 2

Representative operational elements of engineering. In electrical engineering, Ohm’s Law states that current (I) is proportional to voltage (V) according to the resistance (R) of the element. In mechanical engineering, Hooke’s Law states that displacement (x) is proportional to applied force (F) according to the spring constant (k) of the element. In chemical engineering, the vapor-liquid equilibrium equation relates pressure (P) to the mole fraction of the i^th component in the liquid (x_i) and vapor (y_i) phases based on its fugacity coefficient (φ_i), activity coefficient (γ_i), and vapor pressure (p_i^vap). In systems bioengineering, the law of mass action is required to describe the conversion of substrate (S) to product (P) catalyzed by an enzyme (E) and involving an enzyme-substrate intermediate (ES). The kinetics of the reaction involve a system of differential equations with rate parameters describing reversible ES formation (k₁, k₋₁) and catalytic conversion (k_cat).

Fig. 3

Different intersections of biology and engineering. (A) Bottom-up approach of synthetic biology. (B) Top-down and middle-out approaches of systems biology.