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 two 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 efforts 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 efforts 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.

Current projects:

• Developer Cell: A modular, extensible chassis for building synthetic cells (Alfred P. Sloan Foundation)
• Design and Implementation of Multi-Component Synthetic Cells (ARO/ICB)
• Control of Functional Bioenabled Materials using Synthetic Cells (ARO/ICB)
• Center for Harnessing Microbiota from Military Environments (CHARMME) (ARO)
• Rules of Composition in Synthetic Biology Across Scales of Complexity: Theory and Tools (AFOSR)

Recent journal papers:

• Impact of Chemical Dynamics of Commercial PURE Systems on Malachite Green Aptamer Fluorescence (Zoila Jurado, Richard M. Murray, Submitted, ACS Synthetic Biology, 2024)
• A Field-Deployable Arsenic Sensor Integrating Bacillus Megaterium with CMOS Technology (Chelsea Y Hu, John B McManus, Fatemeh Aghlmand, Elin M Larsson, Azita Emami, Richard M Murray, Submitted, ACS Synthetic Biology, 2024)
• Engineering the soil bacterium Pseudomonas synxantha 2-79 into a ratiometric bioreporter for phosphorus limitation (Elin M. Larsson, Richard M. Murray, Dianne K. Newman, ACS Synthetic Biology, 2024)
• Development of cell-free transcription-translation systems in three soil Pseudomonads (Joseph T. Meyerowitz, Elin M. Larsson, Richard M. Murray, To appear, ACS Synthetic Biology, 2024)
• Addressable and adaptable intercellular communication via DNA messaging (John P. Marken and Richard M. Murray, Nature Communications, 14:2358, 2023)
• 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)

... 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 UAVs, autonomous driving, and space systems.

Current projects:

• Layered T&E for Safety-Critical Autonomous Systems (AFOSR)

Recent papers:

• Flow-Based Synthesis of Reactive Tests for Discrete Decision-Making Systems with Temporal Logic Specifications (Josefine B. Graebener, Apurva S. Badithela, Denizalp Goktas, Wyatt Ubellacker, Eric V. Mazumdar, Aaron D. Ames, Richard M. Murray, Submitted, IEEE Transactions on Robotics, 2024)
• Specifying and Analyzing Networked and Layered Control Systems Operating on Multiple Clocks (Inigo Incer, Noel Csomay-Shanklin, Aaron Ames, Richard M. Murray, To appear, 2024 Conference on Decision and Control (CDC))
• Efficient local validation of partially ordered models via Baysian directed sampling (Kellan Moorse and Richard Murray, Submitted, 2024 American Control Conference (ACC))
• Pacti: Scaling Assume-Guarantee Reasoning for System Analysis and Design (Inigo Incer, Apurva Badithela, Josefine Graebener, Piergiuseppe Mallozzi, Ayush Pandey, Sheng-Jung Yu, Albert Benveniste, Benoit Caillaud, Richard M. Murray, Alberto Sangiovanni-Vincentelli, Sanjit A. Seshia, Submitted, ACM Transactions on Cyber-Physical Systems (TCPS), Aug 2023)
• 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))

... further results