Bioscience for renewable resources and clean growth

Bioscience for an integrated understanding of health

Category: Standard Studentships

Engineering recombinant protein expression in plants to generate clinically relevant therapeutic proteins and vaccines

Project No. 2358

PRIORITY PROJECT

Primary Supervisor

Dr Andrew Simkin – University of Kent

Co-Supervisor(s)

Prof Matthew Terry – University of Southampton

Prof Mark Smales – University of Kent

Summary

Vaccines, antibodies and other biotherapeutic proteins are now commonly used for the treatment of infectious diseases and non-communicable diseases such as diabetes, autoimmune disease, arthritis, psoriasis, haemophilia and cancers.

Due to strong market demand, these biopharmaceutical recombinant proteins are typically produced on an industrial scale either by microbial fermentation or from mammalian cell culture. Engineering recombinant protein expression in plants is a viable cost competitive option to produce these high value products. Here we will bring together the expertise and know-how of a world-leading group in biotherapeutic protein production with leading expertise in plant biotechnology to open up innovative ways to generate new protein factories for biomedical and animal vaccine applications in the UK. The research programme will address the challenge of (1) targeting therapeutic proteins to plant organelles for successful assembly of a functional product, (2) stably transforming plant tissue as a means of long-term production and investigation of yield and product quality, and (3) developing the tools and technologies to produce plant based vaccines and therapeutic proteins in the UK alongside identifying target therapeutic proteins for future study. Overall objective: To establish tomato fruit as a source of biotherapeutic proteins in the UK, validating constructs for use by transient expression in tobacco and providing new technologies to explore plant based high value biotherapeutic production.
WP1. Generation of constructs for expression in plant tissue by Golden Gate DNA assembly
WP2. Plant cultivation and agrobacterium-mediated transient transformation of Nicotina benthamiana and confirmation of gene expression by qRT-PCR and western blotting
WP3. Production and verification of transgenic tomato plants expressing recombinant proteins in fruit
WP4. Purification of clinically valuable proteins by affinity chromatography (LigaTrap (IgA) or His-Tag
WP5. Verification of recombinant protein activity.