Biomanufacture and characterisation of the potentially therapeutic glycoprotein, factor H

A four-year BBSRC-supported Industrial CASE PhD studentship is available at the University of Edinburgh and the Edinburgh-based biotechnology company, Ingenza Ltd, starting in September 2013. This exciting project will suit a graduate in Biochemistry, Biological Chemistry, Molecular Biology, Biotechnology or a related discipline. An upper second-class (or better) BSc (Hons) degree will be a requirement.

The project will be conducted under the academic supervision of Professor Paul Barlow, with industrial supervision provided by Dr Ian Fotheringham. The work, at the cutting edge of biomanufacturing, will focus on the production in recombinant cells of the potentially therapeutic plasma glycoprotein, factor H (FH), which is a regulator of the human complement system. Administration of this 155-kDa glycoprotein to patients could prevent age-related macular degeneration and fatal kidney-related conditions arising from loss of complement regulation.

The challenge is to create a version of FH that is suitable for clinical trials. This will involve engineering the N-glycosylation machinery of the expression host to link mammalian-like N-glycans to specific side chains on FH. Partially humanised glycans could also be conjugated with polymers to improve solubility, half-life and immune tolerance. The project will involve a partnership between biomolecular scientists, clinicians (at the Centre for Inflammation Research in Edinburgh’s Medical School) and experts in biomanufacturing. The student will work both in the Schools of Biological Sciences and Chemistry at the University and in Ingenza's state-of-the-art protein-production facilities.

Training will be provided through the expertise of the collaborating supervisors and their research groups and technical teams. The student will gain skills in gene design, DNA manipulation and recombinant protein production, fermentation and cell culture, protein purification, glycobiology, bioconjugation, and characterisation using a wide range of biophysical, biochemical and immunological techniques. A particular benefit of the collaborative arrangement will be training in current good manufacturing practice, good laboratory practice, and project design and management in a commercial environment. The student will also benefit from experience of the working practices and integrated team structure of Ingenza, a rapidly growing biotechnology organisation.

The student will also benefit from the high-level training programme in core biosciences and generic skills organised in the School of Biological Sciences and through the East of Scotland Biological Sciences Doctoral Training Programme.