Glycoengineering toolkit for designer prebiotics and antibiotics
Glycans are one of the four primary macromolecules (i.e., nucleic acids, proteins, glycans, and lipids) of all living systems. However, glycans have not received sufficient attention from the biochemical engineering & life science disciplines. This has limited our understanding of how cellular systems function and how to engineer glycans to better control living systems. The role of glycans can be better understood through systematically creating model systems that help uncover the ‘sweet’ rules governing the synthesis, deconstruction, as well as structure-function relationships of these complex macromolecules.
We engineer CAZymes and develop chemoenzymatic methods to synthesize glycans and glycoconjugates. We utilize computational protein design and directed evolution methods to engineer a wide range of glycosidic-bond synthesizing CAZymes (e.g., transglycosidases, glycosynthases, and glycosyltransferases). E.g., we are studying CAZymes for synthesis of bespoke human milk oligosaccharides and plant polysaccharides. We develop novel synthetic biology tools (i.e., promoters, aptazymes) and utilize bio/nanotechnology tools (i.e., liposomes, nanodiscs) to advance the broader field of glycosciences & glycoengineering.
Continuous manufacturing & process analytics for biologics
There has been an emergent need to advance continuous manufacturing bioprocesses for production of low cost but high-quality biotherapeutics like monoclonal antibodies (mAbs). We are developing novel process analytical technology (PAT) to autonomously monitor critical quality attributes (CQAs) of mAbs like N-linked glycosylation (e.g., N-GLYcanyzer). We utilize mechanistic mammalian cell culture process models and advanced PAT process control to monitor and control mAb glycosylation in real-time to enable continuous drug biomanufacturing.