The modelling and synthesis of chemical reaction networks

Whitby, M

Abstract:: Biochemical systems have been influenced, altered, and engineered to produce a myriad of complex behaviours that have far reaching consequences in the realization of computational models and in applications such as pharmaceuticals and cell networks. However, unlike producing desired behaviours in digital systems, the mechanics behind biochemical systems are complex and poorly understood. In particular, gaps in our understanding of the behaviour of cell mechanics or synthetic molecular syst...
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APA Style

Whitby, M. (2020). The modelling and synthesis of chemical reaction networks [PhD thesis]. University of Oxford.

MLA Style

Whitby, M. The Modelling and Synthesis of Chemical Reaction Networks. 2020. University of Oxford, PhD thesis.

Chicago Style

Whitby, M. 2020. “The Modelling and Synthesis of Chemical Reaction Networks.” PhD thesis, University of Oxford.
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Authors

+ Whitby, M More by this author

Division:: MPLS
Department:: Computer Science
Department:: Oxford University
Role:: Author

Contributors

+ Kwiatkowska, M

Role:: Supervisor

+ Engineering & Physical Sciences Research Council More from this funder

Grant:: OUCL/2015/MANW

DOI:: 10.5287/ora-rj6moqpjb
Type of award:: DPhil
Level of award:: Doctoral
Awarding institution:: University of Oxford

Language:: English
Keywords:: SMT-ODE solving

Biochemical Controllers

Chemical Reaction Networks
Subjects:: Biochemical Controllers

SMT-ODE Solving

Chemical Reaction Networks
UUID:: uuid:b71d5649-c235-41c7-a835-14cc5b89a281
Deposit date:: 2020-01-18
ARK identifier:: ark:/29072/ora_b71d5649c23541c7a83514cc5b89a281

Related item:: PID Control of Biochemical Reaction Networks
Description:: Principles of feedback control have been shown to naturally arise in biological systems and successfully applied to build synthetic circuits. In this work we consider Biochemical Reaction Networks (CRNs) as a paradigm for modelling biochemical systems and provide the first implementation of a derivative component in CRNs. That is, given an input signal represented by the concentration level of some species, we build a CRN that produces as output the concentration of two species whose difference is the derivative of the input signal. By relying on this component, we present a CRN implementation of a feedback control loop with Proportional-Integral-Derivative (PID) controller and apply the resulting control architecture to regulate the protein expression in a microRNA regulated gene expression model.
Related item:: Syntax-Guided Optimal Synthesis for Chemical Reaction Networks
Description:: We study the problem of optimal syntax-guided synthesis of stochastic Chemical Reaction Networks (CRNs) that plays a fundamental role in design automation of molecular devices and in the construction of predictive biochemical models. We propose a sketching language for CRNs that concisely captures syntactic constraints on the network topology and allows its under-specification. Given a sketch, a correctness specification, and a cost function defined over the CRN syntax, our goal is to find a CRN that simultaneously meets the constraints, satisfies the specification and minimizes the cost function. To ensure computational feasibility of the synthesis process, we employ the Linear Noise Approximation allowing us to encode the synthesis problem as a satisfiability modulo theories problem over a set of parametric Ordinary Differential Equations (ODEs). We design and implement a novel algorithm for the optimal synthesis of CRNs that employs almost complete refutation procedure for SMT over reals and ODEs, and exploits a meta-sketching abstraction controlling the search strategy. Through relevant case studies we demonstrate that our approach significantly improves the capability of existing methods for synthesis of biochemical systems and paves the way towards their automated and provably-correct design.
Related item:: Chemical reaction network designs for asynchronous logic circuits
Description:: Chemical reaction networks (CRNs) are a versatile language for describing the dynamical behaviour of chemical kinetics, capable of modelling a variety of digital and analogue processes. While CRN designs for synchronous sequential logic circuits have been proposed and their implementation in DNA demonstrated, a physical realisation of these devices is difficult because of their reliance on a clock. Asynchronous sequential logic, on the other hand, does not require a clock, and instead relies on handshaking protocols to ensure the temporal ordering of different phases of the computation. This paper provides novel CRN designs for the construction of asynchronous logic, arithmetic and control flow elements based on a bi-molecular reaction motif with catalytic reactions and uniform reaction rates. We model and validate the designs for the deterministic and stochastic semantics using Microsoft’s GEC tool and the probabilistic model checker PRISM, demonstrating their ability to emulate the function of asynchronous components under low molecular count.

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Copyright holder:: Whitby, M

Licence:: Terms and Conditions of Use for Oxford University Research Archive

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The modelling and synthesis of chemical reaction networks

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The modelling and synthesis of chemical reaction networks

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