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Next-Generation Synthetic Biology Tools

Principal Supervisor: Professor John McCarthy

Co-supervisor: Dr Munehiro Asally

PhD project title: Next-Generation Synthetic Biology Tools

University of Registration: University of Warwick

Project outline

Synthetic Biology is a new area of science and engineering that promises to radically change our understanding of fundamental life processes and to provide solutions to important challenges in medicine, food security, energy, biotechnology and the environment. In this project, you will have the opportunity to build an entirely new platform of tools that will feature in the next generation of cell engineering. Up to now, the components used to build genetic circuits have comprised almost exclusively transcriptional elements, including promoters, transcriptional activators/repressors, terminators, etc. Limitations associated with purely transcriptional circuitry tend to include slow switching kinetics, suboptimal dynamic range of induction/suppression, and problems with robustness and predictability. Moreover, there are relatively few ‘orthogonal’ regulatory promoters available for the important industrial microorganism Saccharomyces cerevisiae.

You will extend the scope of Synthetic Biology circuitry to include posttranscriptional componentry, both at the RNA and protein levels. For example, you will be able to re-engineer the yeast pheromone mating signalling pathway to regulate translation of target mRNAs in response to external ligands, thus providing extremely fast switching of gene expression without the need to modulate transcription. This broadly applicable system will manifest fast switching kinetics and an exceptional dynamic range of translation activity. The project will include detailed characterization of this new category of bioengineering tool. The McCarthy group is internationally renowned for its expertise in the analysis and engineering of posttranscriptional gene expression and provides a highly informed and supportive environment for PhD students.

BBSRC Strategic Research Priority: Molecules, cells and systems

Techniques that will be undertaken during the project:

These will include the use of state-of-the-art methods involving CRISPR, synthetic DNA synthesis and genomic assembly, quantitative analysis of engineered cellular systems using advanced imaging (fluorescence microscopy, flow cytometry), mass spectrometry, and rational design of membrane receptors.

Contact: Professor John McCarthy, University of Warwick