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(BBSRC DTP CASE) Production of complex biologics: Host capacity analysis and capability engineering

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  • Full or part time
    Dr N Dixon
    Prof R Breitling
    Dr J Winterburn
  • Application Deadline
    Applications accepted all year round

Project Description

This project will utilise next generation synthetic biology regulatory tools, to enhance the production and secretion of complex multimeric protein-based biologics from bacterial hosts. RNA-based regulatory tools (riboswitches) have been developed that control gene expression at the level of translation initiation [1-3]. To date we have used these tools to match our biotechnological demand to host cell synthetic capacity, for example matching expression rates to secretion capacity and inner membrane protein biogenesis allowing enhanced periplasmic secretion and production of recombinant inner membrane protein [4]. This studentship project will seek to co-express and secrete commercially and clinically important multimeric protein-based biologics, such as F(abs), F(ab’)2, and T-cell receptors. In order to do this we will employ a combined synthetic biology design approach coupled with a systems analysis (transcriptomics) approach, to allow us to develop new capabilities and understand the underlying stress responses/capacity limitations. In collaboration with Cobra Biologics Ltd based in the UK this project will provide training in cutting-edge biotechnology, namely synthetic biology enabled host engineering, stress response engineering, and bio-processing engineering important for future careers in both academic and industrial R&D.

Qualification
Applications are invited from UK/EU nationals. Candidates from outside of the UK must have resided in the UK for 3 years prior to commencing the PhD in order to be eligible to apply. 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])

Funding Notes

This is a potential CASE studentship to be funded via the BBSRC Doctoral Training Programme. Projects under this scheme are competitively funded; ie there are more projects advertised than available. Please make direct contact with the Principal Supervisor to arrange to discuss the project and submit an online application form as soon as possible. There is no set closing date, projects will be removed as soon as they are filled.

References

[1] Dixon et al 2010 Reengineering orthogonally selective riboswitches Proc Natl Acad Sci USA. p 2830
[2] Dixon et al 2012 Orthogonal riboswitches for tuneable coexpression in bacteria. Angew Chem Int Ed Engl. p3620
[3] Morra et al 2016 Dual transcriptional-translational cascade permits cellular level tuneable expression control.
Nucleic Acids Res. e21
[4] Morra et al 2017 Optimization of Membrane Protein Production Using Titratable Strains of E. coli. Methods Mol Biol. p83


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