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Production of complex biologics: Host capacity analysis and capability engineering

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

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]. Previously 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 PhD 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. 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.

Contact for further Information:



https://dixonlab.org/

https://www.research.manchester.ac.uk/portal/neil.dixon.html

Qualifications:

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or the overseas equivalent) in a related subject area.

Funding Notes

Applications are invited from self-funded students. For UK/EU tuition fees are £15,000 and International are £29,500 for 2018/19 academic year.

Please select PhD Biological Chemistry on the online application form.

View Website

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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