Research Overview

This page contains a brief summary of my group's current research activities, broken up into the two main areas. More information is available on the individual project pages below and also in the recent publications from my group.

Analysis and Design of Biomolecular Feedback Systems

Feedback systems are a central part of natural biological systems and an important tool for engineering biocircuits that behave in a predictable fashion. The figure at the right gives a brief overview of the approach we are taking in the area of synthetic biology. There are three main elements to our current research:

• Synthetic cells - Advances in synthetic biology and molecular sciences have substantially advanced our ability to produce genetically-programmed synthetic cells from molecular components. These e↵orts provide techniques for the bottom-up construction of cell-like systems that can provide scientists with new insights into how natural cells work and harness the power of biology to create nanoscale, biomolecular machines. Work in the US through the Build-A-Cell consortium and similar e↵orts in other countries have established communities of researchers interested in pursuing the construction of synthetic cells, and these activities are an exciting pathway for exploration of the rules of life. The long term goal of our research is to create genetically-programmed synthetic cells consisting of multiple subsystems operating in an integrated fashion. Unlike more traditional synthetic biology approaches, synthetic cells are non-living: they make use of genetic elements provided by biology, but they do not replicate, mutate, or evolve. Applications range from synthesis of bio-compatible materials, to environmental monitoring and remediation, to self-assembly of complex multi-cellular machines. Pursuing this goal requires fundamental research in biological engineering, aimed at moving from creation of clever biomolecular devices to systematic specification, design, integration, and testing of circuits, subsystems, cells, and multi-component systems.

• Biocircuit modeling and design tools - Current approaches in synthetic biology rely on tuning of devices and circuits to work in a specific set of conditions, including the host organism, growth conditions, genetic context, and many other factors. The consequence of this approach is that a device, circuit, or pathway that works in one chassis or environmental context is not likely to work in a different chassis or set of environmental conditions without redesign and tuning. Depending on this application, the lack of robustness for the desired function can slow or even prevent the deployment of synthetic biology technologies, especially in those situations where robustness to context is required by the application. We are tackling this challenge by making use of tools from control and dynamical systems to provide design rules and a computational framework that allows designers to assess robustness of their designs and to evaluate compensation mechanisms designed to enhance robustness. These techniques will build on existing modeling and design tools (e.g. BioCRNpyler), but will integrate representations of biological context to allow distributions of responses to be computed as used as a means of assessing whether a device or circuit will function robustly across chassis and environmental contexts.

• Soil synthetic biology - We are developing an "open source" toolkit for soil synthetic with the goal of bootstrapping a larger effort that would enable the use of engineered microbes to understand and modulate the complex dynamics of the rhizosphere. We are identifying and characterizing genetically tractable microbes capable of long-term persistence; creating a toolbox of genetic parts for gene circuits and pathways in soil conditions; and designing, building, and testing stimulus-response circuits operating in soil. Long-term applications include engineering microbial communities to optimize nutrient uptake and improve survival against environmental hazards such as drought, toxins, or pathogens.

Current projects:

• Center for Harnessing Microbiota from Military Environments (CHARMME) (ARO)
• Rules of Composition in Synthetic Biology Across Scales of Complexity: Theory and Tools (AFOSR)
• Multi-Layer, Composable and Programmable Biomolecular Circuits for Microbial Consortia (Army Research Office)
• Deciphering the Rules of Nucleus Architecture with Synthetic Cells and Organelles (NSF)
• Engineering Reliable Genetic Circuits for Characterization and Remediation of Soil Ecologies (Army Research Office)
• Developing Standardized Cell-Free Platforms for Rapid Prototyping of Synthetic Biology Circuits and Pathways (NSF)

Recent journal papers:

• BioCRNpyler: Compiling chemical reaction networks from biomolecular parts in diverse contexts (William Poole, Ayush Pandey, Zoltan Tuza, Andrey Shur, Richard M. Murray, PLoS Computational Biology, 18(4), e1009987, 2022)
• Layered Feedback Control Overcomes Performance Trade-Off in Synthetic Biomolecular Networks (Chelsea Hu, Richard M. Murray, Nature Communications 13(1):1-13, 2022)
• Robustness guarantees for structured model reduction of dynamical systems with applications to biomolecular models (Ayush Pandey, Richard M. Murray, International Journal on Robust and Nonlinear Control (IJRNC), 1-29, 2022)
• A MATLAB toolbox for modeling genetic circuits in cell-free systems (Vipul Singhal, Zoltan A. Tuza, Zachary Z. Sun, Richard M. Murray, Synthetic Biology, 6(1):ysab007, 2021)
• Control Theory for Synthetic Biology: Recent Advances in System Characterization, Control Design, and Controller Implementation for Synthetic Biology (Victoria Hsiao, Anandh Swaminathan, and Richard M. Murray, IEEE Control Systems Magazine, 38(3):32-62 , June 2018)
• Cell-free and in vivo characterization of Lux, Las, and Rpa quorum activation systems in E. coli (Andrew Halleran, Richard M. Murray, ACS Synthetic Biology, 7(2):752–755, 2017)
• Recursively constructing analytic expressions for equilibrium distributions of stochastic biochemical reaction networks (X. Flora Meng, Ania-Ariadna Baetica, Vipul Singhal, Richard M. Murray, Royal Society Interface, 14(130), 2017)
• Biophysical Constraints Arising from Compositional Context in Synthetic Gene Networks (Enoch Yeung, Aaron J. Dy, Kyle B. Martin, Andrew H. Ng, Domitilla Del Vecchio, James L. Beck, James J. Collins, Richard M. Murray, Cell Systems, 5(1):11–24.e12, 2017)

... further results

Design of Reactive Protocols for Networked Control Systems

We are investigating the specification, design and verification of distributed systems that combine communications, computation and control in dynamic, uncertain and adversarial environments. Our goal is to develop methods and tools for designing control policies, specifying the properties of the resulting distributed embedded system and the physical environment, and proving that the specifications are met. In our past work, we have developed a promising set of results in automatic synthesis of protocols for hybrid (discrete and continuous state) dynamical systems that are guaranteed to satisfy the desired properties even in the presence of environmental action. The desired properties are expressed in the language of temporal logic, and the resulting system consists of a discrete planner that plans, in the abstracted discrete domain, a set of transitions of the system to ensure the correct behaviors, and a continuous controller that continuously implements the plan. More recently, we have shifted our focus to design of specifications -- including horizontal and vertical contracts for multi-agent, layered control systems -- and operational test and evaluation of complex control systems that react to environmental conditions. Application areas include autonomous driving, vehicle management systems, and distributed multi-agent systems.

Current projects:

• Layered T&E for Safety-Critical Autonomous Systems (AFOSR)
• Safety-Critical Cyber-Physical Systems: From Validation & Verification to Test & Evaluation (NSF)

Recent papers:

• Leveraging Classification Metrics for Quantitative System-Level Analysis with Temporal Logic Specifications (Apurva Badithela, Tichakorn Wongpiromsarn, Richard M Murray, To appear, 2021 Conference on Decision and Control)
• Synthesis of Static Test Environments for Observing Sequence-like Behaviors in Autonomous Systems (Apurva Badithela, Richard M. Murray, Submitted, 2021 NASA Formal Methods (NFM))
• Limits of probabilistic safety guarantees when considering human uncertainty (Richard Cheng, Richard M. Murray, Joel W. Burdick, Submitted, 2021 Conference on Decision and Control (CDC))
• Rules of the Road: Safety and Liveness Guarantees for Autonomous Vehicles (Karena X. Cai, Tung Phan-Minh, Soon-Jo Chung, Richard M. Murray, To appear, IEEE T. Robotics, 2023)
• Invariant Sets for Integrators and Quadrotor Obstacle Avoidance (Ludvig Doeser, Petter Nilsson, Aaron D. Ames, and Richard M. Murray, 2020 American Control Conference (ACC))
• Intermittent Connectivity for Exploration in Communication-Constrained Multi-Agent Systems (Filip Klaesson, Petter Nilsson, Aaron D. Ames, Richard M. Murray, 2020 International Conference on Cyberphysical Systems (ICCPS))
• Counter-example Guided Learning of Bounds on Environment Behavior (Yuxiao Chen, Sumanth Dathathri, Tung Phan-Minh, Richard M. Murray, 2019 Conference on Robot Learning (CoRL))
• Contracts of Reactivity (Tung Phan-Minh and Richard M. Murray, Submitted, Int'l Conf on Formal Modeling and Analysis of Timed Systems (FORMATS) 2019)

... further results