Biotechnology, Bioprocessing and Biopharmaceuticals: Gene Expression in Industrially-Relevant Systems
Therapeutic regimes have been revolutionised by the development of technologies for the isolation of specific genes and for the introduction and expression of these genes in suitable host cells. There is an ever increasing list of proteins which are generated from recombinant DNA technology; many of these proteins make treatment possible for clinical conditions previously beyond the scope of alternative strategies. For optimal effectiveness, many therapeutic proteins require post-translational modifications which can only be performed fully by mammalian cells. Thus, much attention has been focused by academic and industrial groups towards optimisation of mammalian cell systems (Bioprocessing) as hosts for high level expression of commercially-valuable recombinant proteins (Biopharmaceuticals). It is clear that the pipeline of biopharmaceuticals contains a number of potential “blockbuster” products. However, the biochemistry and physiology of host cell systems play profound roles in the level of expression and fidelity of the recombinant protein and can determine the market effectiveness for potential biopharmaeuticals.
Research in the Dickson lab focuses on increased molecular understanding of industrially-relevant mammalian cell expression systems and how such information can be used to enhance the commercial viability of bioprocessing. In particular we seek to define how individual components within the pathway from gene to secreted biopharmaceutical interact to determine the effectiveness of an overall process. Our “systems-level” approach amalgamates basic aspects of gene expression and host cell physiology with the interaction between cells and their culture environment – ie bioprocessing from gene to production. Projects to engineer improved bioprocesses, many with strong links with industry, involve a wide range of molecular biological, cell biological and biochemical techniques and include:-
- Analysis of chromatin-level control of recombinant gene expression
- Molecular definition of stable cell lines
- ‘Omics characterisation of effective mammalian cell bioprocessing
In addition to his individual research portfolio, Alan Dickson is Director of the Centre of Excellence in Biopharmaceuticals (COEBP). The COEBP, initially funded by the European Regional Development Fund (ERDF) and the North West Regional Development Agency (NWDA) integrates the activities of the University of Manchester across basic and applied research linked to the biopharmaceuticals industrial and academic sector. Alan is also Co-Director (with Prof Mark Smales at the University of Kent) of BioProNET, a BBSRC Network in Industrial Biotechnology & Bioenergy, co-funded by EPSRC.