Development and application of an advanced glycan production platform using synthetic biology / engineering biology

"BACKGROUND: Glycoconjugates make excellent vaccines but are expensive to produce, glycoengineering of bacterial cells promises a cost-effective alternative.
CHALLENGE: Glycan biosynthesis genes have typically been cloned whole ('en bloc') from the native organism into E. coli, with original regulatory sequences intact. However, gene expression within these pathways has been optimised by natural selection for synthesis in the native host and is unlikely to be optimal for heterologous production in an unrelated organism, where it may cause toxicity, metabolic burden, mutations and failure to express.
SOLUTION: We recently developed and validated a platform for combinatorial construction and optimisation of glycan biosynthesis and polymerisation genes. Instead of constructing individual pathway designs, a large 'library' of many millions of variants is constructed, varying the expression of each enzyme combinatorially.
AIM: During the rotation the student will apply cutting edge synthetic biology and glycoengineering tools and techniques to assemble a novel glycan synthesis locus using our established platform, and utilise established screening techniques to identify the most promising candidates. To fit in the nine-week timeframe, a pre-identified glycan cluster will be targeted, for which the supervisors will design and source synthetic DNA ready for the start of the project."