Evolving novel yeast expression hosts for large scale biomaterial and biologic production

Evolving novel yeast expression hosts for large scale biomaterial and biologic production Protein-based structures are finding increasing use as either therapeutics or as scaffolds in regenerative medicine due to their specificity and sustainability. One current barrier to translating their use to the clinic is the need to be able to generate the proteins in large quantities at an economical cost in an organism other than E. coli. The ability to generate either post-translationally modified or 'conjugation-ready' proteins in a eukaryotic host at scale is therefore highly desirable and a major challenge for Synthetic/Engineering Biology. In collaboration with our Industrial partner, Phenotypeca Ltd (https://phenotypeca.com/), we plan an exciting research programme to generate new Baker's yeast strains that provide efficient chassis for the preparation of several different therapeutic proteins that are being developed at Nottingham. The PhD will include training in molecular biology and protein purification, characterisation and modification; bioinformatics; development and evaluation of Baker's yeast strains; chemical and enzyme-mediated ligand conjugation; identification of post-translational modifications using a variety of analytical techniques and pre-clinical evaluation of the product proteins.
The research will be conducted in the recently completed, State of the Art labs in the Biodiscovery Institute at the University of Nottingham (https://www.nottingham.ac.uk/research/research-areas/biodiscovery-institute/biodiscovery-institute.aspx#) that brings together 850 researchers from 5 different Schools in biological and chemical sciences together with medicine. It also houses several companies including Phenotypeca's R&D, who also have facilities at BioCity Nottingham (https://biocity.co.uk/locations/biocity-nottingham/), allowing the successful applicant continuous access to their facilities and expertise throughout the PhD. The academic supervisors for the project are Prof. Neil R. Thomas from the School of Chemistry and Prof. Sara Goodacre from the School of Life Sciences. They have longstanding interests in the development of bioinspired materials based on proteins for healthcare applications and have co-supervised a number of successful PhD students who have been able to access the highly complementary training in their laboratories in protein engineering, gene mining and bioinformatics. Their ongoing collaboration is strengthened by the involvement of Dr Chris Finnis from Phenotypeca in this project. He brings a wealth of experience in the commercial use of yeast in therapeutic protein production and is one of the founders of Phenotypeca.