Resource-aware mammalian cell engineering
File(s)
Author(s)
Di Blasi, Roberto
Type
Thesis
Abstract
Resource competition within engineered cells is a significant source of unpredictability in cell engineering, causing altered cellular physiology and unexpected behaviour of genetic circuits. While we now have a clear picture of how resource competition impacts microbial physiology, together with a plethora of mitigation strategies to address these issues, our understanding of how resource competition comes into play in engineered mammalian systems is currently limited.
Here we present our contribution to advancing the current understanding of resource competition in mammalian systems. Using a synthetic biology approach, we investigated resource allocation profiles in engineered mammalian cells. We identified resource bottlenecks in key cellular pathways, developed tools for appropriate quantification of cellular stress in resource-depleted engineered cells, and proposed resource-informed construct design as a new mitigation strategy. Whenever possible, we showed how our work can be useful to support cell engineering applications and correct interpretation of foundational biology experiments.
Here we present our contribution to advancing the current understanding of resource competition in mammalian systems. Using a synthetic biology approach, we investigated resource allocation profiles in engineered mammalian cells. We identified resource bottlenecks in key cellular pathways, developed tools for appropriate quantification of cellular stress in resource-depleted engineered cells, and proposed resource-informed construct design as a new mitigation strategy. Whenever possible, we showed how our work can be useful to support cell engineering applications and correct interpretation of foundational biology experiments.
Version
Open Access
Date Issued
2023-07-05
Date Awarded
01/10/2023
License URL
Advisor
Ceroni, Francesca
Sponsor
Imperial College London
Publisher Department
Chemical Engineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)