CBMNet and IBCarb awarded BBSRC International Workshop Award
BBSRC has identified industrial biotechnology and bioenergy as high-level priority areas in its Delivery Plan for 2016-2020. Supporting the BBSRC to achieve its strategic goals, this focused workshop will identify the science and technological barriers that need to be addressed in order to harness the potential of plant ‘cell factories’ for producing biopharmaceuticals. A CBMNet-driven symposium (Manchester, September 2017) brought together key players from Canada, the EU and the UK, to discuss scientific and commercial opportunities and challenges in this space. The goal now is to regroup, with a more focused set of individuals, to refine the landscape and to identify opportunities for collaborative R&D projects involving academia and industry in the UK and Canada. These aims are synergistic with those of CBMNet and IBCarb in the UK, and with the Canadian Glycomics Network, GlycoNet.
Organisms produce glycosylated proteins for multiple purposes (e.g. stabilising protein structure; interacting with receptors; self-recognition; etc.). There is a significant body of work on mammalian and yeast cells – both to understand the mechanisms of glycosylation and to manipulate it to synthesise desired glycoforms (including biopharmaceutical applications). Although plants are increasingly being used as a platform for commercial manufacturing of proteins, our knowledge of the glycosylation systems of plants is incomplete. For example, the secretory pathway (the location where glycosylation takes place) and consequences of manipulation thereof are poorly investigated. However, the understanding of basic mechanisms is of utmost importance, because it has a significant impact on the expression level (yield) and quality of a glycoprotein product.
An introductory workshop driven by CBMNet was attended by 22 participants from the UK, Canada and the EU. Expertise spanned cell membrane biology, cell membrane transporters, yeast and bacterial glycosylation, glycobiology, protein secretion, structure/function of a set of nucleotide sugar transporters, glycomics, plant biotechnology, and in vitro remodelling of glycans on therapeutic proteins, enabled a focus on sharing knowledge and gaining a deeper understanding of the native plant glycosylation machinery and the manipulation thereof for the production of proteins with optimised functions. The workshop identified the differences and common features in different species (i.e. mammalian, yeast, bacterial), as a basis to better understand and control protein glycosylation in plants. Identifying potential bottlenecks in the transport of a proteins through the secretory pathway was also considered.
The goal now, through a slimmed-down working group, is to define potential ways forward that will overcome yield- and quality-restricting bottlenecks in plant glycoprotein production processes. This will require the development fundamental understanding, coupled with the generation and deployment of tools to manipulate pathways and processes.