Synthetic biology is a rapidly growing field set to make profound impact in numerous industries including manufacturing, healthcare, agriculture, and sustainable energy, as well as our fundamental understanding of life itself. Progress has been hindered, however, by the difficulty in engineering biological systems reliably. One promising approach is to use cell-free expression systems . These are in vitro systems that mimic the cellular environment and can be integrated with microfluidic technologies to rapidly prototype and screen synthetic gene circuits, prior to their deployment in vivo. The amount of control over perturbations and the composition of the system additionally enables precise mathematical modelling and inference of the system’s behaviour, which is necessary for rational approaches to gene circuit design.
Cell-free systems have not yet fulfilled their potential as prototyping platforms, however, due to lack of data and understanding of the differences between the cell-free chassis and a real host cell . This project aims to meet that need by developing automated characterisation of a large number of common parts and circuits in both cell-free and living cells, using the resources available at the Edinburgh Genome Foundry. Identifying which parts behave consistently across the two platforms will allow cell-free systems to be more reliably used for rapid prototyping; and seeing where the differences are may point towards more fundamental gaps in our understanding of synthetic biology.
The ideal candidate will be a highly motivated biologist interested in quantitative approaches to gene circuit engineering, or a physicist/engineer interested in applying their skills to a wet-lab environment. Experience in any of the following areas is highly desirable: molecular biology, microbiology and cell culture, microfluidics, microscopy, programming, lab automation.
The project will be jointly supervised by Dr Nadanai Laohakunakorn https://nadanai263.github.io/
) from the School of Biological Sciences, and Dr Filippo Menolascina from the School of Engineering.
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If you would like us to consider you for one of our scholarships you must apply by 5 January 2020 at the latest.
Swank, Z., Laohakunakorn, N., and Maerkl, S. J. Cell-free gene-regulatory network engineering with synthetic transcription factors. PNAS 116:13, 5892-5901 (2019)
Chappell, J., Kirsten, J., and Freemont, P. S. Validation of an entirely in vitro approach for rapid prototyping of DNA regulatory elements for synthetic biology. Nucleic Acids Res. 41:5, 3471-3481 (2013)