Optimising the production of cysteine-bonded therapeutic proteins (Newcastle, iCASE award)
To remain competitive in the rapidly expanding global bioprocessing industry, it is vital to maintain a programme of continual innovation. This requires close collaboration between academia and industry, including the training of young scientists with experience in both sectors. The complementary skills of Newcastle University and Cobra Biologics will provide a PhD training programme with a combination of academic and industrial disciplines and translational opportunities that distinguishes it from a solely University-based programme. Currently, a variety of human and humanised proteins have unrealised potential for development as therapeutics because of bottlenecks in their synthesis. While recombinant therapeutic proteins are produced in a variety of hosts, microbial systems are favoured due to their ease of refactoring and lack of inappropriate glycosylation. Approximately 30% of target therapeutic proteins cannot be produced in E. coli and similar hosts because they misfold as insoluble inclusion bodies. Bacillus secretion represents a bacterial system with innate refolding capabilities that not only impacts on the range of the proteins produced but also reduces costs but simplifying downstream processing. This project extends a previous successful collaboration between the Newcastle Centre for Bacterial Cell Biology and Cobra Biologics. The effectiveness of the previous collaboration is evidenced by a joint patent on the enhancement of Bacillus protein secretion and a set of host strains that overcome many secretion bottlenecks. These strains are already in great demand by academic researchers and the biomanufacturing industry and a key selling point of this project is that it will add to this collection by providing a solution for the production of disulfide-bonded therapeutic proteins. The existing strains, together with the knowledge and IP gained from their construction and use, represent a valuable resource for the current project. The student will benefit from a supervisory team that includes scientists from academia and industry, and with expertise ranging from leading-edge molecular biological research to Good Manufacturing Practice (GMP) biomanufacturing and knowledge transfer.
For further information see the website: http://www.ncl.ac.uk/camb/
Please submit a full CV and covering letter directly to [email protected]
This is a 4 year BBSRC iCASE studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£14,057 for 2015-16). The PhD will start in September 2016. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support. There are 2 stages to the application process.
Nicolas, P et al., (2012) Condition-dependent transcriptome reveals high-level regulatory architecture in Bacillus subtilis. Science 335, 1103-1106.