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Optimisation of mammalian cell factories for manufacture of biological medicines

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

Project Description

Biopharmaceuticals (eg. antibodies, other protein- and nuclei-based medicines) are produced in cellular systems and are used for treatment and cure of many diseases. These are products that show how industrial biotechnology can have life-changing consequences for patients. The past 25 years has seen massive technical breakthroughs in the use of mammalian cell lines as factories for production of recombinant secreted protein (as medicines) and nucleic acids (for gene therapies). The next generation of products under development challenge existing cell factories and projects in the Dickson laboratory are focused on understanding molecular limitations and the means to increase the capability to make specific product types (exemplified by the references below)

Specific projects are designed around the interest of specific students and will incorporate modern molecular technologies (e.g. systems biology assessment of cell phenotype and development of models of cellular processes and the subsequent use of synthetic biology to modify cells and develop next generation hosts). Many projects are multi-disciplinary and involve other members of academic staff and industrial collaborators. The fundamental target for all studies is how the engagement of the cell factory with maximisation of production of commercially-valuable biopharmaceuticals can be achieved. You will learn cutting-edge technical skills at both sites and gain from exposure to the commercial context of the work in the Dickson lab group. The Manchester Institute of Biotechnology (http://www.mib.ac.uk) is an excellent academic environment for research in biopharmaceuticals with unique facilities and multidisciplinary research programmes housed in the Centre of Excellence in Biopharmaceuticals, http://www.coebp.manchester.ac.uk

In pursuing a project in the Dickson lab to a successful conclusion, you will be likely to master mammalian cell culture, vector construction and characterisation, transfection for transient and stable cell line production, cell line selection, characterisation of protein and nucleic acid expression and quality, biochemical and microscopic characterisation of molecular trafficking. We always set project objectives to be ambitious but doable and extremely exciting from which you will gain a very wide range of training that will give you excellent research and transferrable skills to move to the subsequent stages of your career. Data generated in the project will have the potential for publication and has commercial implications for optimisation of production of novel format biopharmaceuticals in the future.

Applicants should have or expect to achieve at least a 2.1 honours degree in a Biologically-related subject, Chemical Engineering, or a related subject. Successful candidates will be enrolled in the 3-year Ph.D. program of the School of Chemical Engineering and Analytical Science.

References

Sellick, CA, Croxford, AS, Maqsood, AR, Stephens, GM, Westerhoff, HV, Goodacre, R & Dickson, AJ (2015) "Metabolite profiling of CHO cells: Molecular reflections of bioprocessing effectiveness" Biotechnol J 10: 1434-1445.
Betts, Z & Dickson, AJ (2016) “Ubiquitous Chromatin Opening Elements (UCOEs) effect transgene position and expression stability in CHO cells following methotrexate (MTX) amplification” Biotechnology J. 11: 554-564.
Hussain. H, Fisher, DI, Abbott, WM, Roth, RG & Dickson, AJ (2017) “Use of a protein engineering strategy to overcome limitations in the production of ‘difficult to express’ recombinant proteins” Biotechnol. Bioeng. 114: 2348-2359.
Maldonado-Agurto, R & Dickson, AJ (2018) “Multiplexed digital mRNA expression analysis profiles system-wide changes in mRNA abundance and responsiveness of UPR-specific gene expression changes during batch culture of recombinant Chinese Hamster Ovary cells” Biotechnol. J. DOI: 10.1002/biot.201700429.
Hussain, H, Fisher, DI, Roth, RG, Abbott, WM, Carballo-Amador, MA, Warwicker, J & Dickson, AJ (2018) “A protein chimera strategy supports production of a model ‘difficult-to-express’ recombinant target” FEBS Lett. 592: 2499-2511.

How good is research at University of Manchester in Aeronautical, Mechanical, Chemical and Manufacturing Engineering?
Chemical Engineering

FTE Category A staff submitted: 33.90

Research output data provided by the Research Excellence Framework (REF)

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