Enhancing Primary Recovery Efficiency of Recombinant Proteins from CHO Cell Culture Harvest Material via a Knowledge of Cellular Lipid Contents and their Fluctuations

4 Year Collaborative EPSRC sponsored PhD studentship between the University of Kent (Canterbury), University College London (UCL) and Lonza Biologics (Slough).

The project will focus upon characterising the diversity of the Chinese hamster ovary (CHO) cellular lipid profile during fed-batch culture and how this changes over time and between clones, and subsequently influences primary recovery efficiency. The influence of cellular lipids on recombinant mammalian cell productivity and primary recovery steps has largely been ignored, despite the fact that ever-increasing amounts of cell biomass is being achieved in the bioreactor and lipids constitute up to half of the dry mass of mammalian cells and can impact upon the efficiency of primary recovery steps. This project will (i) define the CHO cellular lipid profile for a model system and seek to gain an understanding of how this changes during culture and at harvest, (ii) develop knowledge as to whether the target recombinant protein influences the lipid profile and the ease with which these are removed, (iii) seek an understanding of the relationship between lipid components in the cell culture supernatant and primary recovery efficiency, and (iv) design bioprocesses to limit lipid impact on primary recovery steps. The principal aims of this work are therefore to test the over-arching hypothesis that identification and characterization of the major cellular lipid components of CHO cells will allow the development of a knowledge based approaches to design more efficient or alternative purification strategies and the rational selection and/or engineering of host cell lines to limit the levels of potentially problematic lipids during primary recovery processes.

The project will directly supplement on-going research at the University of Kent, UCL and Lonza Biologics and as such will be a highly complementary project that harnesses the established competencies of all collaborating partners, whilst the student will be at the interface of this relationship and able to gain experience from both perspectives and skill bases. The experimental approaches will include molecular biology, protein analytical technologies, cell culture, protein biochemistry/analysis, downstream purification and primary recovery approaches. This is a rare opportunity for a student to undertake basic biological research and then apply the findings in an industrial setting. The studentship will involve undertaking research at both the academic and industrial site although it is anticipated that the majority of the time the student will be based at the University of Kent. The student will be required to undertake some research work at UCL and complete a formal training requirement of attending 18 training events taken from a mix of compulsory EPSRC CDT courses at UCL supplemented by some from the host Institution (Kent).

The successful candidate will have a degree (or expect to) at 2(i) or higher in Biochemistry, Biology, Biotechnology, Biochemical Engineering or a related subject. The School of Biosciences at the University of Kent is a part of the Faculty of Sciences and has dedicated Molecular Biology, Protein Characterisation and Bioprocessing laboratories that are a recognized strength of the School and University. The School is therefore able to provide a world-class research infrastructure to support our research on recombinant protein production. UCL is a world class research-led university, ranked seventh in the world by the QS World University Rankings (2016). UCL Biochemical Engineering is acknowledged as the UK National Centre of Excellence for Bioprocessing it conducts highly integrated basic science and engineering research with the goal of improving the UK manufacturing competitiveness in the sector. Lonza is one of the world’s leading and most-trusted suppliers to the pharmaceutical, biotech and specialty ingredients markets. Lonza harness science and technology to create products that support safer and healthier living and that enhance the overall quality of life (see http://www.lonza.com/custom-manufacturing/capabilities-overview.aspx).

To apply for this project please submit an on-line application for the PhD Biochemistry at https://www.kent.ac.uk/courses/postgraduate/229/biochemistry. Please enter the project title as the proposed research topic and enter Prof Mark Smales as supervisor. For the research proposal please enter "as advertised". Please include a cv and a covering letter.

Applications must be received by Wednesday 22nd March 2017. Interviews will be held at the University of Kent the week commencing Monday 27th March 2017.

Informal enquiries can be addressed to Prof Mark Smales in the School of Biosciences; email [Email Address Removed].