HIGH-BANDWIDTH IDENTIFICATION AND COMPENSATION OF HYSTERETIC DYNAMICS

Ph.DDOCTOR OF PHILOSOPH

Robustness of networked systems to unintended interactions with application to engineered genetic circuits

A networked dynamical system is composed of subsystems interconnected through prescribed interactions. In many engineering applications, however, one subsystem can also affect others through "unintended" interactions that can significantly hamper the intended network's behavior. Although unintended interactions can be modeled as disturbance inputs to the subsystems, these disturbances depend on the network's states. As a consequence, a disturbance attenuation property of each isolated subsystem is, alone, insufficient to ensure that the network behavior is robust to unintended interactions. In this paper, we provide sufficient conditions on subsystem dynamics and interaction maps, such that the network's behavior is robust to unintended interactions. These conditions require that each subsystem attenuates constant external disturbances, is monotone or "near-monotone", the unintended interaction map is monotone, and the prescribed interaction map does not contain feedback loops. We employ this result to guide the design of resource-limited genetic circuits. More generally, our result provide conditions under which robustness of constituent subsystems is sufficient to guarantee robustness of the network to unintended interactions

Abstractions, Analysis Techniques, and Synthesis of Scalable Control Strategies for Robot Swarms

Tasks that require parallelism, redundancy, and adaptation to dynamic, possibly hazardous environments can potentially be performed very efficiently and robustly by a swarm robotic system. Such a system would consist of hundreds or thousands of anonymous, resource-constrained robots that operate autonomously, with little to no direct human supervision. The massive parallelism of a swarm would allow it to perform effectively in the event of robot failures, and the simplicity of individual robots facilitates a low unit cost. Key challenges in the development of swarm robotic systems include the accurate prediction of swarm behavior and the design of robot controllers that can be proven to produce a desired macroscopic outcome. The controllers should be scalable, meaning that they ensure system operation regardless of the swarm size. This thesis presents a comprehensive approach to modeling a swarm robotic system, analyzing its performance, and synthesizing scalable control policies that cause the populations of different swarm elements to evolve in a specified way that obeys time and efficiency constraints. The control policies are decentralized, computed a priori, implementable on robots with limited sensing and communication capabilities, and have theoretical guarantees on performance. To facilitate this framework of abstraction and top-down controller synthesis, the swarm is designed to emulate a system of chemically reacting molecules. The majority of this work considers well-mixed systems when there are interaction-dependent task transitions, with some modeling and analysis extensions to spatially inhomogeneous systems. The methodology is applied to the design of a swarm task allocation approach that does not rely on inter-robot communication, a reconfigurable manufacturing system, and a cooperative transport strategy for groups of robots. The third application incorporates observations from a novel experimental study of the mechanics of cooperative retrieval in Aphaenogaster cockerelli ants. The correctness of the abstractions and the correspondence of the evolution of the controlled system to the target behavior are validated with computer simulations. The investigated applications form the building blocks for a versatile swarm system with integrated capabilities that have performance guarantees

Principles for Designing Robust and Stable Synthetic Microbial Consortia

Engineering stable microbial consortia with robust functions are useful in many areas, including bioproduction and human health. Robust and stable properties depend on proper control of dynamics ranging from single cell-level to population-environment interactions. In this thesis, I discuss principles of building microbial consortia with synthetic circuits in two design scenarios. First, for one microbial population, strong disturbances in environments often severely perturb cell states and lead to heterogeneous responses. Single cell-level design of control circuits may fail to induce a uniform response as needed. I demonstrate that cell-cell signaling systems can facilitate coordination among cells and achieve robust population-level behaviors. Moreover, I show that heterogeneity can be harnessed for robust adaptation at population-level via a bistable state switch. Second, multi-pecies consortia are intrinsically unstable due to competitive exclusion. Previous theoretical investigations based on models of pairwise interactions mainly explored what interaction network topology ensures stable coexistence. Yet neglecting detailed interaction mechanisms and spatial context results in contradictory predictions. Focusing on chemical-mediated interaction, I show that detailed mechanisms of chemical consumption/accumulation and chemical-induced growth/death, interaction network topology and spatial structures of environments all are critical factors to maintain stable coexistence. With a two population-system, I demonstrate that the same interaction network topology can exhibit qualitatively different or even opposite behaviors due to interaction mechanisms and spatial conditions.</p

Architecture, Design, and Tradeoffs in Biomolecular Feedback Systems

A core pursuit in systems and synthetic biology is the analysis of the connection between the low-level structure and parameters of a biomolecular network and its high-level function and performance. Elucidating this mapping has become increasingly feasible as precise measurements of both input parameters and output dynamics become abundant. At the same time, cross-pollination between biology and engineering has led to the realization that many of the mathematical tools from control theory are well-suited to analyze biological processes. The goal of this thesis is to use tools from control theory to analyze a variety of biomolecular systems from both natural and synthetic settings, and subsequently yield insight into the architecture, tradeoffs, and limitations of biological network. In Chapter 2, I demonstrate how allosteric proteins can be used to respond logarithmically to changes in signal. In Chapter 3, I show how control theoretic techniques can be used to inform the design of synthetic integral feedback networks that implement feedback with a sequestration mechanism. Finally, in Chapter 4 I present a novel simplified model of the E. coli heat shock response system and show how the the mapping of circuit parameters to function depends on the network's architecture. The unifying theme of this research is that the conceptual framework used to study engineered systems is remarkably well-suited to biology. That being said, it is important to apply these tools in a way that is informed by the molecular details of biological processes. By combining structural and biochemical data with the functional perspective of engineering, it is possible to understand the architectural principles that underlie living systems.</p

Benelux meeting on systems and control, 23rd, March 17-19, 2004, Helvoirt, The Netherlands

Book of abstract

Design and analysis of DNA controllers

Reliable biochemical implementations of linear controllers can provide a large set of tools for the design and analysis of control in Synthetic Biology. Theoretical frameworks are now available to represent feedback control systems as chemical reaction networks which can be readily translated into equivalent nucleic acid-based chemistry. However, the development of tools for constructing and analysing such controllers is still in its infancy. Nucleic acid-based chemistry is a strong candidate framework for the construction of future synthetic biomolecular control circuits. The capacity of strand displacement reactions with Deoxyribonucleic Acid (DNA) to implement analogue signal processing in vitro and in vivo makes them a promising candidate to embed synthetic feedback control circuitry in biomolecular environments. However, little progress has so far been made in developing the requisite theoretical machinery to inform the systematic design of feedback controllers in this context. Here, the potential complexity of such controllers is extended significantly by showing how time-delays, numerical differentiation (to allow proportional-integral-derivative control), and state feedback may be implemented via chemical reaction network-based designs. This work also provides a number of foundational theoretical results on the equilibria, stability, and dynamics of nucleic acid controllers, and the analysis highlights the many interesting and unique characteristics of this important new class of feedback control systems. In particular, that the implementation of feedback controllers using DNA strand displacement reactions introduces additional nonlinear dynamics, even in the case of purely linear control designs, and a robust design of the linear system does not imply the robustness of its chemical implementation. The robustness of the controllers to experimental uncertainty is analysed with the structured singular value (µ) analysis tool, which is extended with a model of how parametric uncertainty in the system affects the location of its equilibrium. This framework provides more reliable results than sampled based statistical methods, where analysis via Monte Carlo simulation fails to uncover the worst-case uncertainty combination found by µ-analysis. The implementations of the examples and controllers in nucleic acid-based chemistry are simulated and checked using the Visual DSD simulation package, a bespoke software tool for simulating nucleic acid-based circuits