Mechanistic mathematical models for the design of synthetic biological systems : DNA recombination, recombinase-based temporal logic gates and antibiotic production

• Main Author: Bowyer, Jack E.
• Published: University of Warwick 2018
• Subjects: 620; QH301 Biology
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.731455

Synthetic biology is the design and implementation of novel biological devices via the application of engineering principles to biological systems research. Mathematical modelling is an invaluable tool in developing our understanding of biological system dynamics and characterising small parts and circuits for the assembly of higher-level systems. In this thesis, mathematical modelling approaches are applied to three biological circuits of interest. A novel mechanistic model of the DNA recombination reactions comprising a genetic switch reveals the input criteria and operational specifications required of a digital data storage module. Specific layering of the components comprising recombinase-based genetic switches can provide cellular Boolean logic operations. A novel mechanistic model of a two-input temporal logic gate is able to simulate and predict in vivo dynamical responses captured by a large experimental dataset. Experimental implementation of recombinase-based circuitry is unpredictable and can lead to lengthy development times, providing clear evidence of the advantages of utilising mathematical models in synthetic biology. Antibiotic resistance has become one of the most prominent challenges facing medicine today, placing immense importance on the characterisation of new natural products. The rst detailed mathematical model of the methylenomycin A producing gene cluster in the bacterium Streptomyces coelicolor is developed through the application of model selection to a large set of candidate system architectures. Mathematical models presented in this thesis can be adapted and expanded to suit many different experimental conditions and system responses, facilitating the design of novel synthetic biological circuitry.