Engineering synthetic gene circuits in light of host constraints: metabolic control and evolution. Engineered microbial systems have a range of potential applications in healthcare, the chemicals industry and environmental science. However, host microbe constraints often lead to degraded functionality or even complete failure of genetic devices. Here we developed a unified dynamic mathematical framework which captures all aspects of the cell’s finite resource economy, including metabolic constraints, ribosomal limitations and growth mediated feedback. We use this framework to design new control strategies which act to enhance both yield and growth of microbial cell factories. Our results show that at by accounting for host constraints we can actually simplify the controller design as the cell’s natural feedback mechanisms reinforce the strength of synthetic regulation. We couple our host design framework with evolutionary simulations to investigate how to enhance long term performance of gene circuits and show that whilst negative feedback has potential to significantly improve circuit longevity the resource consumption of the control system can reverse this benefit. We make recommendations for engineering control systems which ensure enhanced long-term performance in light of evolutionary pressures.Biography. Alexander's work lies at the interface between systems engineering and biotechnology. After initially reading for a degree in natural sciences, specialising in genetics and systems biology, he joined the UK's first synthetic biology doctoral training centre between the universities of Bristol, Oxford and Warwick before joining the University of Warwick’s School of Engineering for his PhD focused on designing translational control systems. His postdoc focused on applying control theoretic tools to improve the performance of gene circuits and he carried out a short Innovation Fellowship working with Ingenza Ltd to apply these methods to metabolic pathways. In 2021 he won a Royal Academy of Engineering Research Fellowship to develop new design frameworks for the efficient engineering of biological systems within cellular and industrial constraints. His group is now developing a range of methods from deriving models from sparse data, designing metabolic control systems, engineering enhanced recombinant protein production, and simulating gene circuit evolution.Host: Lucia Bandiera, School of Engineering Aug 05 2025 12.00 - 13.00 Engineering synthetic gene circuits in light of host constraints: metabolic control and evolution. Alexander Darlington (University of Warwick) Seminar room 1.08, C.H. Waddington Building, Max born Crescent, Kings Buildings Campus Darlington Group
Engineering synthetic gene circuits in light of host constraints: metabolic control and evolution. Engineered microbial systems have a range of potential applications in healthcare, the chemicals industry and environmental science. However, host microbe constraints often lead to degraded functionality or even complete failure of genetic devices. Here we developed a unified dynamic mathematical framework which captures all aspects of the cell’s finite resource economy, including metabolic constraints, ribosomal limitations and growth mediated feedback. We use this framework to design new control strategies which act to enhance both yield and growth of microbial cell factories. Our results show that at by accounting for host constraints we can actually simplify the controller design as the cell’s natural feedback mechanisms reinforce the strength of synthetic regulation. We couple our host design framework with evolutionary simulations to investigate how to enhance long term performance of gene circuits and show that whilst negative feedback has potential to significantly improve circuit longevity the resource consumption of the control system can reverse this benefit. We make recommendations for engineering control systems which ensure enhanced long-term performance in light of evolutionary pressures.Biography. Alexander's work lies at the interface between systems engineering and biotechnology. After initially reading for a degree in natural sciences, specialising in genetics and systems biology, he joined the UK's first synthetic biology doctoral training centre between the universities of Bristol, Oxford and Warwick before joining the University of Warwick’s School of Engineering for his PhD focused on designing translational control systems. His postdoc focused on applying control theoretic tools to improve the performance of gene circuits and he carried out a short Innovation Fellowship working with Ingenza Ltd to apply these methods to metabolic pathways. In 2021 he won a Royal Academy of Engineering Research Fellowship to develop new design frameworks for the efficient engineering of biological systems within cellular and industrial constraints. His group is now developing a range of methods from deriving models from sparse data, designing metabolic control systems, engineering enhanced recombinant protein production, and simulating gene circuit evolution.Host: Lucia Bandiera, School of Engineering Aug 05 2025 12.00 - 13.00 Engineering synthetic gene circuits in light of host constraints: metabolic control and evolution. Alexander Darlington (University of Warwick) Seminar room 1.08, C.H. Waddington Building, Max born Crescent, Kings Buildings Campus Darlington Group
Aug 05 2025 12.00 - 13.00 Engineering synthetic gene circuits in light of host constraints: metabolic control and evolution. Alexander Darlington (University of Warwick)
