Biological Sciences

PhD Projects

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Project Titles

Supervisor Topic
Prof Susan Rosser A combined omics and synthetic biology approach to enhanced CHO cell biologics production

Project Details

A combined omics and synthetic biology approach to enhanced CHO cell biologics production

Description:

Supervisors:  Prof Susan Rosser (susan.rosser@ed.ac.uk) and Dr Thierry Le Bihan (thierry.lebihan@ed.ac.uk

Interested individuals must follow Steps 1, 2 and 3 at this link on how to applyhttp://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply

 

The CHO cell is the most widely used industrial expression system, which generates ~70% of biopharmaceuticals, including multiple monoclonal antibodies (mAbs), with market value >$100 billion. However, many “difficult-to-express” (DTE) biologics give unpredictably low titres, requiring extensive cell line and process development that adds substantial cost. Productivity can be compromised by transgene suppression and bottlenecks in translation, trafficking, processing or secretion. The metabolic burden imposed by heterologous protein production in mammalian cells is still not well characterized and thus may offer opportunities for further improvement of protein productivity. The aim of the current study is to use metabolomics and proteomics to discover bottlenecks in biologics production in CHO cells and characterize the burden of heterologous protein production under differing growth conditions. This information will provide us with targets for a synthetic biology approach to CHO cell engineering. By engineering CHO lines where we can rapidly and reliably insert transgenes into a known stable, predictable genetic environment we can decrease screening time for stable high production clones. This, combined with control of expression by synthetic transcription factors, will result in more consistent cell culture performance that is as important as yield.

The student will learn cutting edge metabolomics, proteomic and synthetic biology techniques.

The project will be supervised jointly by Prof. Susan Rosser and Drs Thierry LeBihan and Dr Hannah Florance. Prof Rosser is professor of synthetic biology, director of the UK Centre for Mammalian Synthetic Biology (http://www.synbio.ed.ac.uk) and co-director of the Edinburgh Genome Foundry (http://www.genomefoundry.org). Dr Le Bihan leads the proteomics research and Dr Hannah Florance leads the metabolomics research at the centre for Synthetic and Systems Biology (http://www.synthsys.ed.ac.uk) at the University of Edinburgh.

The PhD student will become part of a cohort of students linked to the research of the new UK Centre for Mammalian Synthetic Biology (the ‘Centre’), based at the University of Edinburgh. Through support from the Research Council’s Synthetic Biology for Growth programme and of the BBSRC, EPSRC and MRC, the University has been awarded ~ £18M in funding to establish a national facility for DNA synthesis (the Edinburgh Genome Foundry) and one of six UK Centres of Excellence in Synthetic Biology. More information about our Centre can be found at http://www.synbio.ed.ac.uk and follow us on Twitter @SynthSysEd.

This is an exciting opportunity to be at the cutting edge of this fast moving area of science and technology in world-leading research institutes. We are looking for highly motivated graduates who are enthusiastic about the potential of this new area of science and keen to work across disciplines.

 

 

 

Further Information:

This project is funded through an EPSRC CASE Award in collaboration with the company UCB. It therefore provides an excellent opportunity to work closely with industry professionals including working for at least three months at the company.

 

This opportunity is only open to UK nationals (or EU students who have been resident in the UK for 3+ years immediately prior to the programme start date) due to restrictions imposed by the funding body.

 

Closing date for applications is 30/04/2017

 

 

References:

Subject Area(s):

Synthetic biology, CHO cell engineering, metabolomics, proteomics

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