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(BBSRC DTP) Engineering Novel Allosteric Transcription Factor Recognition: Applications in Bio-catalysis and Synthetic Biology

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  • Full or part time
    Dr N Dixon
    Prof D Leys
    Prof N Turner
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

The aim of this project is to explore the potential of engineering transcription factors (TF) with novel allosteric recognition capabilities, and then to apply these novel TFs in the high-throughput selection of new biocatalysts. TFs can be used for a range of applications for example; screening enzymatic processes for biomass valorisation [1], evolving novel enzymes and strains via Adaptive Laboratory Evolution [2], and detection of environmental pollutants and bio-remediation. This project will seek to engineer the recognition properties of MarR-type TFs to recognise alternative aromatic molecules of both natural and synthetic origin [1], and then apply these novel recognition capabilities to evolve enzymes with new substrate tolerance and catalytic performance characteristics. These novel enzymatic and cellular functionalities will provide potential solutions to a number of socioeconomic drivers and environmental demands such as cultural pressure for global sustainability and provide alternative routes for the production of fine-chemicals products and intermediates.

The PhD student based in Manchester Institute of Biotechnology will be co-supervised by Dr. Neil Dixon, and Profs David Leys, and Nick Turner, and will be focused on i) engineering MarR-type transcriptional factors to recognise a non-natural aromatic chemicals of environmental and industrial importance, ii) applying the engineered TFs to evolve novel enzymatic functionality and optimise bio-catalytic capability, iii) integrating these individual enzymes and TFs into biosynthetic pathways for whole-cell biotransformation, and iv) using synthetic biology tools and principles to engineer the developed pathway.

The student will be trained in broad aspects of biotechnology, microbial gene expression regulation, biocatalysis, directed evolution, microbial fermentation, molecular biology and bio-analytical methods such GC-MS. This project would suit individuals interested in future careers in biotechnology, biocatalysis and bioprocessing.

Qualification
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

Contact for further Information
For more details contact Dr Neil Dixon ([email protected])

http://www.manchester.ac.uk/research/neil.dixon/
https://dixonlab.org/
http://www.manchester.ac.uk/research/david.leys/
http://www.manchester.ac.uk/research/nicholas.turner/

Funding Notes

This project is to be funded under the BBSRC Doctoral Training Programme. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the BBSRC DTP website www.manchester.ac.uk/bbsrcdtpstudentships

References

[1] Taylor ND, Garruss AS, Moretti R, Chan S5, Arbing MA, Cascio D, Rogers JK, Isaacs FJ, Kosuri S, Baker D,
Fields S, Church GM, Raman S. Engineering an allosteric transcription factor to respond to new ligands. Nat
Methods. 2016 13(2):177-83.
[2] Leopoldo F. M. Machado, Neil Dixon Development and substrate specificity screening of an in vivo
biosensor for the detection of biomass derived aromatic chemical building blocks Chemical Communications
(2016), DOI: 10.1039/C6CC04559F
[3] Williams TC, Pretorius IS, Paulsen IT. Synthetic Evolution of Metabolic Productivity Using Biosensors Trends
Biotechnol. 2016 4(5):371-81.

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