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Modelling cellular stress during recombinant protein production for improving upstream biomanufacturing processes


Project Description

Applications are invited for one PhD studentship to work in modelling the stress imposed on host organisms by recombinant protein production for improving predictive capabilities of upstream bioprocess models employed in biomanufacturing practices.
Recombinant proteins are expressed non-endogenously by an organism, and they have wide applications in biotechnology ranging from the biomanufacture of industrially and agriculturally relevant enzymes to therapeutics and the manufacture of biologics. Due to this commercial interest, there is pressure to achieve high yields of high quality protein product by the host cells. However, all biological systems are optimised for their own survival, and not for the production of a heterologous entity, which is the main goal, when an organism as used as a host for the production of a recombinant protein. Therefore, this process of heterologous protein expression, particularly in a state of overproduction, creates a huge burden on the cell. The host has difficulty to achieve a high quality product, i.e. a correctly processed protein, under the stress imposed by high production demand. This stress triggers responses within the host to cope with the accumulation of the low quality, and therefore undesirable, product. These responses range from the formation of inclusion bodies by prokaryotic hosts such as bacteria, to the induction of unfolded protein response by eukaryotic hosts such as yeast and mammalian cells.
This studentship is intended to enable the development of quantitative models of this stress response and the utilisation of these models in the improvement and optimisation of upstream biomanufacturing processes of recombinant protein production. The successful candidate will be based at the Department of Biochemical Engineering at University College London. The work will predominantly constitute the implementation of a working model, which demonstrates a mechanistic understanding of stress associated with heterologous protein production, and its incorporation within data-driven models of upstream biomanufacturing processes available in-house with the aim of expanding their predictive capability. The project will include occasional work in the laboratory for verification of the predictive capabilities of the proposed models, or for the determination of relevant model parameters.

Applicants should have (or expect to obtain by the start date) at least a good 2.1 degree (and preferably a Master’s degree) in Engineering or Physical Sciences, preferably with demonstrable experience or background in Biological Sciences. This PhD will be multidisciplinary, straddling both biochemical engineering and modelling and data science. The successful candidate should have: strong analytical skills and aptitude for numerical modelling and programming as well as for understanding cellular mechanisms.

The starting date for this PhD will be January 2020. To apply for this studentship, please send your two-page CV and cover letter by email to Ms Andrea Kezer, CDT Manager & Postgraduate Programmes Manager () to arrive no later than 12pm on Friday, 29th November 2019. For queries related to this position, please contact Dr Duygu Dikicioglu (Supervisor: ) and Prof Gary Lye (Advisor: ).

The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.

Funding Notes

This research project has funding attached. It is only available to UK citizens or those EU citizens who have been resident in the UK for a period of 3 years or more (restrictions apply). The studentship covers the full cost of UK/EU tuition fees, plus a tax free stipend of £17,009 p.a. for four years.

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