In the past several years, the technology for de novo creating biomolecular systems and for measuring key quantities has come to a point in which quantitative analysis and design of biological networks is now possible. While a modular approach to analyze and design networked dynamical systems has proven critical in most control theory applications, it is still subject of intense debate whether a modular approach is viable in biological networks. The dynamics of these networks are nonlinear and therefore addressing this question requires the use of tools from nonlinear control theory. In this talk, we present a theoretical framework to quantify the extent of modularity in biomolecular networks and to establish modular analysis and design techniques. Specifically, we address the fundamental question of modularity by demonstrating that loading effects are found in biomolecular systems, just like in many engineering systems. These effects, which we call retroactivity, can be severe and alter the behavior of a module upon interconnection, undermining modular behavior. We introduce a system concept to explicitly model retroactivity and determine interconnection rules that account for retroactivity by calculating equivalent network descriptions, just like Thevenin's theorem does for linear electrical circuits. By using singular perturbation techniques, we further provide an approach that exploits the distinctive structure of biomolecular networks to design biomolecular insulating amplifiers. These devices attenuate retroactivity by solving a disturbance rejection problem, thus restoring modular behavior and enabling a bottom-up design approach in synthetic biology. We provide experimental demonstrations of our theory and illustrate a concrete biological realization of an insulating amplifier in living cells.
Domitilla Del Vecchio received the Ph. D. degree in Control and Dynamical Systems from the California Institute of Technology, Pasadena, and the Laurea degree in Electrical Engineering from the University of Rome at Tor Vergata in 2005 and 1999, respectively. From 2006 to 2010, she was an Assistant Professor in the Department of Electrical Engineering and Computer Science at the University of Michigan, Ann Arbor. In 2010, she joined the Department of Mechanical Engineering and the Laboratory for Information and Decision Systems (LIDS) at the Massachusetts Institute of Technology (MIT), where she is currently an associate professor. She is a recipient of the Donald P. Eckman Award from the American Automatic Control Council (2010), the W. M. Keck Career Development Professorship, MIT (2010), the NSF Career Award (2007), the Crosby Award, University of Michigan (2007), the American Control Conference Best Student Paper Award (2004), and the Bank of Italy Fellowship (2000). Her research interests include nonlinear control theory with application to biological and transportation networks.
