Exploring the design of biological circuits using dCas-based regulators

Abstract

Genetic circuits are fundamental to how an organism responds to its environment, something that synthetic biologists aim to mimic. To do this, orthogonal proteins that interact with and modulate the expression of a gene are needed. To date these proteins are generally mined from other organisms, which hampers the design and creation of larger circuits by causing metabolic burden. To get around this, circuit designers are increasingly looking towards dCas-regulators, to act as programmable transcription factors. To date optimality in design with dCas-regulators has not been explored, especially in any great detail. As such, this thesis aims to characterise the strengths and weaknesses of dCas-regulation through a combination of computational modelling and experimental techniques. Using this characterisation, a model generator was constructed to explore topological optimality in dCas-regulator design. This thesis provides the basis for a deeper understanding of design with dCas-regulators and provides a steppin

Date of Award	4 Feb 2025
Original language	English
Awarding Institution	University of Bristol
Supervisor	Thomas E Gorochowski (Supervisor) & Lucia Marucci (Supervisor)