Production of a Modular Toolkit for Creating Prosthetic Gene Networks within Yeast

As the field of synthetic biology is maturing, it is becoming clear that it will have a major impact in clinical therapy, particularly with the design of prosthetic gene networks, which are being specifically built for the autonomous treatment of human disease without the limitations of traditional pharmacotherapies. These closed-loop biosynthetic sensor/actuator devices can functionally integrate and interface with the host metabolism in order to detect and manage disease states with the production of an appropriate therapeutic in situ. Using yeast as an engineerable testbed, I am generating a platform for developing prosthetic gene networks in a rational, bottom-up manner by creating a highly-characterised and standardised set of modular components, along with a well-defined workflow for rapidly iterating the design/ build/ test cycle. It is believed this new framework will yield systems with improved predictability for tuning to patient idiosyncrasies, provide a cheaper and faster strategy for creating prosthetic gene networks, and generate a variety of parts and devices that can be reused for future projects. To achieve this, I am refactoring major components of the native yeast pheromone response pathway under synthetic regulation, in an effort to identify the best strategy for linking medically relevant G-protein coupled receptors to an appropriate therapeutic response. Initial work has revealed that regulation of individual components can be used to alter the dose response characteristics of the signalling pathway, which can be used as an approach to network tuning.