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 research:

• Modeling and analysis - we are working to develop rigorous tools for analyzing the phenotype of complex biomolecular systems based on data-driven models. We are particularly interested in systems involving feedback, since causal reasoning often fails in these systems due to the interaction of multiple components and pathways. Work in this are includes system identification, theory for understanding the role of feedback, and methods for building and analyzing models built using high-throughput datasets.
• Rapid prototyping' - we are making use of computational models and cell-free systems to develop design-oriented methods for efficient implementation and characterization of biological circuits in a systematic fashion. Our goal is to help enable rapid prototyping and debugging of biomolecular circuits that can operate either in vitro or in vivo.
• Biocircuit design - engineered biological circuits required a combination of system-level principles, circuit-level design and device technologies in order to allow systematic design of robust systems. We are working on developing new device technologies for fast feedback as well as methods for combining multiple feedback mechanisms to provide robust operation in a variety of contexts. Our goal is to participate in the development of systematic methods for biocircuit design that allow us to overcome current limitations in device complexity for synthetic biocircuits.

Current projects:

• Multi-Layer, Composable and Programmable Biomolecular Circuits for Microbial Consortia (Army Research Office)
• Engineering Reliable Genetic Circuits for Characterization and Remediation of Soil Ecologies (Army Research Office)
• Deciphering the Rules of Nucleus Architecture with Synthetic Cells and Organelles (NSF)
• Actuation of Synthetic Cells Via Proto-Flagellar Motors (NSF)
• An Open Synthetic Biology Toolkit for Engineering Reliable Genetic Circuits in Microbes in Soil (Resnick Sustainability Institute)
• Developing Standardized Cell-Free Platforms for Rapid Prototyping of Synthetic Biology Circuits and Pathways (NSF)

Recent journal papers:

• 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)
• A population-based temporal logic gate for timing and recording chemical events (Victoria Hsiao, Yutaka Hori, Paul W.K. Rothemund, Richard M. Murray, Molecular Systems Biology, 12: 869, 2016)
• Rapid cell-free forward engineering of novel genetic ring oscillators (Henrike Niederholtmeyer, Zachary Sun, Yutaka Hori, Enoch Yeung, Amanda Verpoorte, Richard M Murray and Sebastian J Maerkl, eLife 2015;10.7554/eLife.09771)
• Characterizing and Prototyping Genetic Networks with Cell-Free Transcription-Translation Reactions (Melissa K Takahashi, Clarmyra A. Hayes, James Chappell, Zachary Z. Sun, Richard M Murray, Vincent Noireaux, Julius B. Lucks, Methods, 15(85):60-72, 2015)

... 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:

• Safety-Critical Cyber-Physical Systems: From Validation & Verification to Test & Evaluation (NSF)
• Formal Methods for V&V and T&E of Autonomous Systems (AFOSR)

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))
• Rules of the Road: Safety and Liveness Guarantees for Autonomous Vehicles (Karena X. Cai, Tung Phan-Minh, Soon-Jo Chung, Richard M. Murray, Submitted, IEEE T. Robotics, July 2021)
• 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))
• Failure-Tolerant Contract-Based Design of an Automated Valet Parking System using a Directive-Response Architecture (Josefine Graebener, Tung Phan-Minh, Jiaqi Yan, Qiming Zhao, Richard M Murray, Submitted, 2021 American Control Conference)
• 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 and 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, and Richard M. Murray, 2019 Conference on Robot Learning (CoRL))

... further results