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.
- 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)
- Engineering Replication-, Growth-, and Division-Deficient E. coli for Safe, Stable and Efficient Function (Rosen Center for Bioengineering)
- Design of Digitally Controlled Bacterial Circuits for Bioenabled Materials (Army Research Lab/Institute for Collaborative Biotechnologies)
- Developing Standardized Cell-Free Platforms for Rapid Prototyping of Synthetic Biology Circuits and Pathways (NSF)
- Engineering Durable Cell-Free Biological Capabilities for Advanced Sensing and Prototyping (Army Research Office)
- Enabling Technologies for Cell-Silicon Interfacing (Army Research Office)
- Fundamental Biological Factors Underlying Human Performance: From Molecular Diagnostics and Detection to Behavior and Systems Biology (Army Research Office)
- Field-Programmable, Recombinase-Based Biomolecular Circuits (Army Research Office)
- Robust Multi-Layer Control Systems for Cooperative Cellular Behaviors (DARPA)
Recent journal papers:
- 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)
- Engineering Transcriptional Regulator Effector Specificity using Computational Design and In Vitro Rapid Prototyping: Developing a Vanillin Sensor (Emmanuel Lorenzo Cornejo de los Santos, Joseph T Meyerowitz, Stephen L Mayo, Richard M Murray, ACS Synthetic Biology, 5(4):287–295, 2016.)
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.
- Assurance for Learning Enabled Systems (DARPA)
- Formal Methods for V&V and T&E of Autonomous Systems (AFOSR)
- VeHICaL: Verified Human Interfaces, Control, and Learning for Semi-Autonomous Systems (NSF)
- Layering assume-guarantee contracts for hierarchical system design (Ioannis Filippidis and Richard M. Murray, Proceedings of the IEEE, 2018)
- Model Predictive Control for Signal Temporal Logic Specifications (Vasumathi Raman, Alexandre Donze ́, Mehdi Maasoumy, Richard M. Murray, Alberto Sangiovanni-Vincentelli and Sanjit A. Seshia, Submitted, IEEE T. Automatic Control (2 Jan 2016))
- Symbolic construction of GR(1) contracts for systems with full information (Ioannis Filippidis and Richard M. Murray, 2016 American Control Conference (ACC))
- Reactive Synthesis from Signal Temporal Logic Specifications (Vasumathi Raman, Alexandre Donze, Dorsa Sadigh, Richard M. Murray and Sanjit A. Seshia, 2015 International Conference on Hybrid Systems: Computation and Control (HSCC))
- Cross-entropy Temporal Logic Motion Planning (Scott C. Livingston, Eric M. Wolff, Richard M. Murray, Submitted, 2015 International Conference on Hybrid Systems: Computation and Control (HSCC))
- A Contract-Based Methodology for Aircraft Electric Power System Design (P. Nuzzo, H. Xu, N. Ozay, J. B. Finn, A. L. Sangiovanni-Vincentelli, R. M. Murray, A. Donze, S. A. Seshia, IEEE Access, 2014. DOI 10.1109/ACCESS.2013.2295764)
- Synthesis of Control Protocols for Autonomous Systems (Tichakorn Wongpiromsarn, Ufuk Topcu and Richard M. Murray, Unmanned Systems, 1(1):21-39 (2013))