Project title: Systems and control for engineering biology

Engineering living “cell factories” enable the production of new therapeutics or sustainable routes to the manufacture of high-value chemicals from agricultural by-products [1]. However, engineering such living factories is complicated due to a lack of a quantitative understanding of how natural host and synthetic engineered processes interact. Natural and engineered processes compete at the metabolic level and gene expression level and impact important processes, such as cell growth. In addition to these cellular constraints, living factories are subjected to industrial constraints (including heterogeneity, fermentation strategy, and cost), which further limit performance in commercial settings, while over time, performance changes due to the impact of evolution.

Our research group tackles outstanding roadblocks to the industrialisation of synthetic biological systems by developing predictive mathematical multi-scale models of cellular processes and fermentation strategy to systems-level microbial growth and factory production performance. We used these methods to engineer autonomous cellular and genetic control systems which integrate the cell’s stress responses and dynamically balance growth and engineered biomanufacturing processes. We are currently applying these approaches in the following projects:

1. Enhancing the production yields of membrane proteins for drug screening.
2. Engineering controllers to manage toxic intermediates production in cell factories producing natural products.
3. Engineering enhanced evolutionary stability in complex gene circuits.
4. Understanding cellular constraints in industrial microbes through optimal experimental design.

These interdisciplinary projects are all supported by ongoing experimental collaborations. Projects in the group are highly flexible, and the ratio of theoretical to experimental work will be tailored to suit the candidate’s background and interests (ranging from completely theoretical to entirely experimental or somewhere in between).

Candidates will have either:
(1) strong systems engineering and/or mathematical skills with good programming skills and a keen interest in applying their skills to an exciting new area. While no formal biological background is required, some prior knowledge of cell and molecular biology would be advantageous.
(2) a strong background in molecular and systems biology with good lab skills and a strong interest in learning or using quantitative approaches. Prior courses in calculus and mathematical biology would be advantageous.

Candidates are encouraged to get in touch with Dr Alexander Darlington to discuss potential projects before making a formal application. Please entitle your email "Prospective Engineering PhD candidate - [Surname]" and attach a short CV.

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The University of Warwick provides an inclusive working and learning environment, recognising and respecting every individual’s differences. We welcome applications from individuals who identify with any of the protected characteristics defined by the Equality Act 2010.

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