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Programmable transcriptional activation engineering in cell-free expression systems


School of Biological Sciences

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Dr N Laohakunakorn , Dr Baojun Wang No more applications being accepted Competition Funded PhD Project (Students Worldwide)

About the Project

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 [1]. 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.

While cell free systems have already been used to prototype a large number of gene circuits using transcriptional repressors, building functional activators has remained elusive, despite their fundamental role in living cells. This project plans to deploy a number of different approaches from in vivo activator engineering and programmable gene regulation [2] to build a repertoire of cell-free activators, forward-engineer a new class of gene circuits based on these parts, and understand the properties and limitations of these newly-engineered cell-free systems.

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, cell culture, microfluidics, microscopy, programming.

The project will be jointly supervised by Dr Nadanai Laohakunakorn (https://nadanai263.github.io/) and Dr Baojun Wang (http://wang.bio.ed.ac.uk/), within the School of Biological Sciences.


Funding Notes

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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.

References

1. Swank, Z., Laohakunakorn, N., and Maerkl, S. J. Cell-free gene regulatory network engineering with synthetic transcription factors. PNAS 116:13, 5892-5901 (2019)
2. Liu, Y., Wan, X., and Wang, B. Engineered CRISPRa enables programmable eukaryote-like gene activation in bacteria. Nature communications 10:3693 (2019)

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