(A*STAR) Bacterial glycosyltransferases for bioengineering of biologics

Within industry, biologics are usually produced in large bioreactors which are subject to slight manufacturing changes in production and purification which induce variations in glycosylation. Variation in glycosylation of bio-therapeutic drugs can have profound effects on its safety and efficacy. Despite its importance, in-vivo control of biologic glycosylation, remains a particularly uncertain process.

Recently, we (Sabine Flitsch and BTI) have been successful in developing an in-vitro glyco-engineering approach using bacterial glycotransferases to a recombinant glycoprotein alpha-1 anti-trypsin. This has significant potential to increase the yield of high quality product after culturing/fermentation. Furthermore, the technology has significant potential to produce higher value, cheaper bio-better products for the clinic. Whilst this is an attractive proposition, much work still is required to develop a scalable process along with analytical development which can compete with current production modalities.

We seek to develop a method to refine a scalable process to increase the hyper-sialylation of recombinant products with the accompanying analytics for validation.

Project Description
The project aims to develop a robust, scalable in-vitro glyco-engineering platform to control the glycosylation of recombinant glycoprotein biologics. This will be performed using bacterial glyco-transferases. The project will also involve developing the necessary glyco-analytics which can be used to monitor processes and quality control for assessment.
Specific Objectives:
1. Development of a cost-effective in-vitro glyco-engineering platform for the hyper-sialylation of therapeutic recombinant glycoproteins
2. Develop a fermentation process to increase the production of bacterial sialyl-transferases important in the hyper glycosylation of therapeutic recombinant glycoproteins.
3. Application of current advanced glyco-analytical approaches to monitor the quality of the glyco-engineered product

Entry Requirements:
Applications should be submitted online and candidates should make direct contact with the Manchester supervisor to discuss their application directly. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.