Richard M. Murray

Richard M. Murray
California Institute of Technology | CIT

About

735
Publications
63,365
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
62,842
Citations

Publications

Publications (735)
Preprint
We provide a new perspective on using formal methods to model specifications and synthesize implementations for the design of biological circuits. In synthetic biology, design objectives are rarely described formally. We present an assume-guarantee contract framework to describe biological circuit design objectives as formal specifications. In our...
Preprint
Full-text available
We present a framework for merging unit tests for autonomous systems. Typically, it is intractable to test an autonomous system for every scenario in its operating environment. The question of whether it is possible to design a single test for multiple requirements of the system motivates this work. First, we formally define three attributes of a t...
Article
Model reduction methods usually focus on the error performance analysis; however, in presence of uncertainties, it is important to analyze the robustness properties of the error in model reduction as well. This problem is particularly relevant for engineered biological systems that need to function in a largely unknown and uncertain environment. We...
Article
A large class of decision making under uncertainty problems can be described via Markov decision processes (MDPs) or partially observable MDPs (POMDPs), with application to artificial intelligence and operations research, among others. Traditionally, policy synthesis techniques are proposed such that a total expected cost or reward is minimized or...
Preprint
In this paper, we investigate formal test-case generation for high-level mission objectives, specifically reachability, of autonomous systems. We use Kripke structures to represent the high-level decision-making of the agent under test and the abstraction of the test environment. First, we define the notion of a test specification, focusing on a fr...
Article
In this paper, we investigate formal test-case generation for high-level mission objectives, specifically reachability, of autonomous systems. We use Kripke structures to represent the high-level decision-making of the agent under test and the abstraction of the test environment. First, we define the notion of a test specification, focusing on a fr...
Preprint
In many autonomy applications, performance of perception algorithms is important for effective planning and control. In this paper, we introduce a framework for computing the probability of satisfaction of formal system specifications given a confusion matrix, a statistical average performance measure for multi-class classification. We define the p...
Article
Full-text available
Increased complexity in cyber-physical systems calls for modular system design methodologies that guarantee correct and reliable behavior, both in normal operations and in the presence of failures. This paper aims to extend the contract-based design approach using a directive-response architecture to enable reactivity to failure scenarios. The arch...
Preprint
Full-text available
Increased complexity in cyber-physical systems calls for modular system design methodologies that guarantee correct and reliable behavior, both in normal operations and in the presence of failures. This paper aims to extend the contract-based design approach using a directive-response architecture to enable reactivity to failure scenarios. The arch...
Preprint
Full-text available
Synthetic biological gene networks are typically conceptualized and visualized as static graphs with nodal and edge dynamics that are time invariant. This conceptualization of biological programming stands in stark contrast to the transient nature of biological dynamics, which are driven by labile biomolecules. Here we demonstrate the use of dynami...
Article
Synthetic biological gene networks are typically conceptualized and visualized as static graphs with nodal and edge dynamics that are time invariant. This conceptualization of biological programming stands in stark contrast to the transient nature of biological dynamics, which are driven by labile biomolecules. Here we demonstrate the use of dynami...
Article
When autonomous robots interact with humans, such as during autonomous driving, explicit safety guarantees are crucial in order to avoid potentially life-threatening accidents. Many data-driven methods have explored learning probabilistic bounds over human agents' trajectories (i.e. confidence tubes that contain trajectories with probability δ), wh...
Preprint
Full-text available
When autonomous robots interact with humans, such as during autonomous driving, explicit safety guarantees are crucial in order to avoid potentially life-threatening accidents. Many data-driven methods have explored learning probabilistic bounds over human agents' trajectories (i.e. confidence tubes that contain trajectories with probability $\delt...
Article
Full-text available
We introduce a MATLAB based simulation toolbox, called txtlsim, for an E. coli based Transcription-Translation (TX-TL) system. This toolbox accounts for several cell-free related phenomena, such as resource loading, consumption, and degradation, and in doing so, models the dynamics of TX-TL reactions for the entire duration of solution phase batch-...
Preprint
Full-text available
The ability to guarantee safety and progress for all vehicles is vital to the success of the autonomous vehicle industry. We present a framework for the distributed control of autonomous vehicles that is safe and guarantees progress for all agents. In this paper, we first introduce a new game paradigm which we term the quasi-simultaneous discrete-t...
Article
The ability to guarantee safety and progress for all vehicles is vital to the success of the autonomous vehicle industry. We present a framework for the distributed control of autonomous vehicles that is safe and guarantees progress for all agents. In this paper, we first introduce a new game paradigm which we term the quasi-simultaneous discrete-t...
Article
We derive phenomenological models of gene expression from a mechanistic description of chemical reactions using an automated model reduction method. Using this method, we get analytical descriptions and computational performance guarantees to compare the reduced dynamics with the full models. We develop a new two-state model with the dynamics of th...
Preprint
Full-text available
We derive phenomenological models of gene expression from a mechanistic description of chemical reactions using an automated model reduction method. Using this method, we get analytical descriptions and computational performance guarantees to compare the reduced dynamics with the full models. We develop a new two-state model with the dynamics of th...
Article
Molecular feedback control circuits can improve robustness of gene expression at the single cell level. This achievement can be offset by requirements of rapid protein expression, that may induce cellular stress, known as burden, that reduces colony growth. To begin to address this challenge we take inspiration by 'division-of-labor' in heterogeneo...
Article
The mammalian gut contains trillions of microbes that interact with host cells and monitor changes in the environment. Opportunistic pathogens exploit environmental conditions to stimulate their growth and virulence, leading to a resurgence of chronic disorders such as inflammatory bowel disease (IBD). Current therapies are effective in less than 3...
Preprint
Full-text available
Molecular feedback control circuits can improve robustness of gene expression at the single cell-level. This achievement can be offset by requirements of rapid protein expression, that may induce cellular stress, known as burden, that reduces colony growth. To begin to address this challenge we take inspiration by ‘division-of-labor’ in heterogeneo...
Preprint
Full-text available
The mammalian gut contains trillions of microbes that interact with host cells and monitor changes in the environment. Opportunistic pathogens exploit environmental conditions to stimulate their growth and virulence, leading to a resurgence of chronic disorders such as inflammatory bowel disease (IBD). Current therapies are effective in less than 3...
Article
In multicellular organisms, cells actively sense, respond to, and control their own population density. Synthetic mammalian quorum sensing circuits could provide insight into principles of population control and improve cell therapies. However, a key challenge is avoiding their inherent sensitivity to “cheater” mutations that evade control. Here, w...
Preprint
Full-text available
In multicellular organisms, cells actively sense, respond to, and control their own population density. Synthetic mammalian quorum sensing circuits could provide insight into principles of population control and improve cell therapies. However, a key challenge is avoiding their inherent sensitivity to “cheater” mutations that evade control. Here, w...
Preprint
Full-text available
We introduce a MATLAB based simulation toolbox, called txtlsim, for an E. coli based Transcription-Translation (TX- TL) system. This toolbox accounts for several cell-free related phenomena, such as resource loading, consumption, and degradation, and in doing so, models the dynamics of TX-TL reactions for the entire duration of batch-mode experimen...
Preprint
Biochemical interactions in systems and synthetic biology are often modeled with Chemical Reaction Networks (CRNs). CRNs provide a principled modeling environment capable of expressing a huge range of biochemical processes. In this paper, we present a software toolbox, written in python, that complies high-level design specifications to CRN represe...
Article
Full-text available
Biochemical interactions in systems and synthetic biology are often modeled with Chemical Reaction Networks (CRNs). CRNs provide a principled modeling environment capable of expressing a huge range of biochemical processes. In this paper, we present a software toolbox, written in python, that complies high-level design specifications to CRN represe...
Preprint
Full-text available
Cells must detect and respond to molecular events such as the presence or absence of specific small molecules. To accomplish this, cells have evolved methods to measure the presence and concentration of these small molecules in their environment and enact changes in gene expression or behavior. However, cells don’t usually change their DNA in respo...
Article
Integral feedback control is commonly used in mechanical and electrical systems to achieve zero steady-state error following an external disturbance. Equivalently, in biological systems, a property known as robust perfect adaptation guarantees robustness to environmental perturbations and return to the pre-disturbance state. Previously, Briatet al....
Preprint
Full-text available
Realizing homeostatic control of metabolites or proteins is one of the key goals of synthetic circuits. However, if control is only implemented internally in individual cells, cell-cell heterogeneity may break the homeostasis on populationlevel since cells do not contribute equally to the production or regulation. New control structures are needed...
Article
Realizing homeostatic control of metabolites or proteins is one of the key goals of synthetic circuits. However, if control is only implemented internally in individual cells, cell-cell heterogeneity may break the homeostasis on populationlevel since cells do not contribute equally to the production or regulation. New control structures are needed...
Article
We present a Python-based software package to automatically obtain phenomenological models of input-controlled synthetic biological circuits that guide the design using chemical reaction-level descriptive models. From the parts and mechanism description of a synthetic biological circuit, it is easy to obtain a chemical reaction model of the circuit...
Preprint
Full-text available
Much of the progress in developing our ability to successfully design genetic circuits with predictable dynamics has followed the strategy of molding biological systems to fit into conceptual frameworks used in other disciplines, most notably the engineering sciences. Because biological systems have fundamental differences from systems in these oth...
Article
Much of the progress in developing our ability to successfully design genetic circuits with predictable dynamics has followed the strategy of molding biological systems to fit into conceptual frameworks used in other disciplines, most notably the engineering sciences. Because biological systems have fundamental differences from systems in these oth...
Preprint
Full-text available
We present a Python-based software package to automatically obtain phenomenological models of input-controlled synthetic biological circuits that guide the design using chemical reaction-level descriptive models. From the parts and mechanism description of a synthetic biological circuit, it is easy to obtain a chemical reaction model of the circuit...
Preprint
Full-text available
We have developed a mathematical framework to analyze the cooperative control of cell population homeostasis via paradoxical signaling in synthetic contexts. Paradoxical signaling functions through quorum sensing (where cells produce and release a chemical signal as a function of cell density). Precisely, the same quorum sensing signal provides bot...
Article
We have developed a mathematical framework to analyze the cooperative control of cell population homeostasis via paradoxical signaling in synthetic contexts. Paradoxical signaling functions through quorum sensing (where cells produce and release a chemical signal as a function of cell density). Precisely, the same quorum sensing signal provides bot...
Preprint
There is a growing interest in building autonomous systems that interact with complex environments. The difficulty associated with obtaining an accurate model for such environments poses a challenge to the task of assessing and guaranteeing the system's performance. We present a data-driven solution that allows for a system to be evaluated for spec...
Chapter
For the synthesis of correct-by-construction control policies from temporal logic specifications the scalability of the synthesis algorithms is often a bottleneck. In this paper, we parallelize synthesis from specifications in the GR(1) fragment of linear temporal logic by introducing a hierarchical procedure that allows decoupling of the fixpoint...
Conference Paper
Full-text available
There is a growing interest in building autonomous systems that interact with complex environments. The difficulty associated with obtaining an accurate model for such environments poses a challenge to the task of assessing and guaranteeing the system's performance. We present a data-driven solution that allows for a system to be evaluated for spec...
Preprint
Full-text available
Rules or specifications for autonomous vehicles are currently formulated on a case-by-case basis, and put together in a rather ad-hoc fashion. As a step towards eliminating this practice, we propose a systematic procedure for generating a set of supervisory specifications for self-driving cars that are 1) associated with a distributed assume-guaran...
Article
Full-text available
Rules or specifications for autonomous vehicles are currently formulated on a case-by-case basis, and put together in a rather ad-hoc fashion. As a step towards eliminating this practice, we propose a systematic procedure for generating a set of supervisory specifications for self-driving cars that are 1) associated with a distributed assume-guaran...
Conference Paper
Full-text available
We present a theory of contracts that is centered around reacting to failures and explore it from a general assume-guarantee perspective as well as from a concrete context of automated synthesis from linear temporal logic (LTL) specifications, all of which are compliant with a contract metatheory introduced by Benveniste et al. We also show how to...
Article
Reinforcement Learning (RL) algorithms have found limited success beyond simulated applications, and one main reason is the absence of safety guarantees during the learning process. Real world systems would realistically fail or break before an optimal controller can be learned. To address this issue, we propose a controller architecture that combi...
Article
Neural networks in real-world applications have to satisfy critical properties such as safety and reliability. The analysis of such properties typically requires extracting information through computing pre-images of the network transformations, but it is well-known that explicit computation of pre-images is intractable. We introduce new methods fo...
Article
Feedback regulation is pervasive in biology at both the organismal and cellular level. In this article, we explore the properties of a particular biomolecular feedback mechanism called antithetic integral feedback, which can be implemented using the binding of two molecules. Our work develops an analytic framework for understanding the hard limits,...
Conference Paper
The phenomenon of parameter (structural) non-identifiability can pose significant challenges to the use of parametrized dynamical models. We demonstrate that, for the case of models being used to transform data across environments, it is possible to derive conditions under which the presence of structural non-identifiability does not hinder our mod...
Conference Paper
Full-text available
As a direct contribution to recent efforts of bringing formal design-by-contract methods to hybrid systems, we introduce a variant of modal interface contract theory based on input/output automata with guarded transitions. We present an algebra of operators for interface composition, contract composition, contract conjunction, contract refinement a...
Conference Paper
Full-text available
We consider the maneuver planning problem for automated vehicles when they share the road with human-driven cars and interact with each other using a finite set of maneuvers. Each maneuver is calculated considering input constraints, actuator disturbances and sensor noise, so that we can use a maneuver automaton to perform higher-level planning tha...
Conference Paper
The bottom up design of genetic circuits to control cellular behavior is one of the central objectives within Synthetic Biology. Performing design iterations on these circuits in vivo is often a time consuming process, which has led to E. coli cell extracts to be used as simplified circuit prototyping environments. Cell extracts, however, display l...
Conference Paper
Paradoxical signaling occurs when the same signaling molecule can trigger antagonistic cell functions. For example, T-Cells secret cytokine IL-2 which promotes T-Cell proliferation and also affects cell death. It has been shown that cells with this signaling capability have bi-stable population dynamics. Cells can achieve identical levels of popula...
Article
We present an automated model reduction algorithm that uses quasi-steady state approximation based reduction to minimize the error between the desired outputs. Additionally, the algorithm minimizes the sensitivity of the error with respect to parameters to ensure robust performance of the reduced model in the presence of parametric uncertainties. W...
Preprint
Full-text available
We present an automated model reduction algorithm that uses quasi-steady state approximation based reduction to minimize the error between the desired outputs. Additionally, the algorithm minimizes the sensitivity of the error with respect to parameters to ensure robust performance of the reduced model in the presence of parametric uncertainties. W...
Preprint
Full-text available
As studies continue to demonstrate how our health is related to the status of our various commensal microbiomes, synthetic biologists are developing tools and approaches to control these microbiomes and stabilize healthy states or remediate unhealthy ones. Building on previous work to control bacterial communities, we have constructed a synthetic t...
Article
As studies continue to demonstrate how our health is related to the status of our various commensal microbiomes, synthetic biologists are developing tools and approaches to control these microbiomes and stabilize healthy states or remediate unhealthy ones. Building on previous work to control bacterial communities, we have constructed a synthetic t...
Article
Full-text available
We study the dynamic and static input–output behavior of several primitive genetic interactions and their effect on the performance of a genetic signal differentiator. In a simplified design, several requirements for the linearity and time-scales of processes like transcription, translation and competitive promoter binding were introduced. By exper...
Preprint
Full-text available
Plasmids are found across bacteria, archaea, and eukaryotes and play an important role in evolution. Plasmids exist at different copy numbers, the number of copies of the plasmid per cell, ranging from a single plasmid per cell to hundreds of plasmids per cell. This feature of a copy number greater than one can lead to a population of plasmids with...
Article
Plasmids are found across bacteria, archaea, and eukaryotes and play an important role in evolution. Plasmids exist at different copy numbers, the number of copies of the plasmid per cell, ranging from a single plasmid per cell to hundreds of plasmids per cell. This feature of a copy number greater than one can lead to a population of plasmids with...
Preprint
Full-text available
In systems and synthetic biology, it is common to build chemical reaction network (CRN) models of biochemical circuits and networks. Although automation and other high-throughput techniques have led to an abundance of data enabling data-driven quantitative modeling and parameter estimation, the intense amount of simulation needed for these methods...
Preprint
Reinforcement Learning (RL) algorithms have found limited success beyond simulated applications, and one main reason is the absence of safety guarantees during the learning process. Real world systems would realistically fail or break before an optimal controller can be learned. To address this issue, we propose a controller architecture that combi...
Article
Cells utilize transcription regulation networks to respond to environmental signals. Network motifs, such as feedforward loops, play important roles in these regulatory networks. In this work, we construct two different functional and modular incoherent type 1 feedforward loop biological circuits in a cell-free transcription-translation system and...
Article
In this work, we propose control improvisation to synthesize voluntary lane-change policy that meets human preferences under given traffic environments. We first train Markov models to describe the lane-change environment for an automated vehicle under assumed traffic patterns. Parameters in the environment model are trained using traffic data and...
Conference Paper
Reinforcement Learning (RL) algorithms have found limited success beyond simulated applications, and one main reason is the absence of safety guarantees during the learning process. Real world systems would realistically fail or break before an optimal controller can be learned. To address this issue, we propose a controller architecture that combi...
Conference Paper
Neural networks in real-world applications have to satisfy critical properties such as safety and reliability. The analysis of such properties typically requires extracting information through computing pre-images of the network transformations, but it is well-known that explicit computation of pre-images is intractable. We introduce new methods fo...
Conference Paper
The fact that genes compete for shared cellular resources poses a fundamental challenge when identifying parameters of genetic parts. A recently developed model of gene expression tackles this problem by explicitly accounting for resource competition. In addition to accurately describing experimental data, this model only depends on a small number...
Conference Paper
In this paper, we use control improvisation to synthesize voluntary lane-change policy that meets human preferences under given traffic environments. We first train Markov models to describe traffic patterns and the motion of vehicles responding to such patterns using traffic data. The trained parameters are calibrated using control improvisation t...
Preprint
Designing synthetic microbial consortia is an emerging area in synthetic biology and a major goal is to realize stable and robust coexistence of multiple species. Cooperation and competition are fundamental intra/interspecies interactions that shape population level behaviors, yet it is not well-understood how these interactions affect the stabilit...