Mucin display

The new cell-based mucin display platform  

Mucins are large highly heterogenous O-glycoproteins covering all internal surfaces of our body and major components in body fluids. Mucins have many functions for our health serving in lubrication and protection of all mucosal surfaces, clearance, neutralization and adhesion of microorganisms and virus, providing a barrier for direct contact to epithelial cells, and serving in entrapment and direction of our microbiomes.

Mucins primarily consist of tandem repeated sequence (TR) domains densely covered with O-glycans, and these O-glycan domains contain the functional cues for the microbiome and innate immune system. However, there are no methods for obtaining human mucin molecules in reasonable purity, with defined glycans, and this has been a fundamental barrier and limitation for studies of mucins and their complex biology.

GlycoDisplay's platform utillise the glycoengineered isogenic HEK293 cell library and enable production of recombinant human mucins with defined glycan structures.

The cell based mucin array allow us to dissect the binding specificities of glycan binding proteins such as lectins, antibodies and microbes. We also offer expression of secreted mucins with distinct O-glycosylation (transient/stable). 

Human mucins with custom-designed O-glycans 

There are 18 distinct human mucins, and these include secreted and cell-membrane attached mucins. GlycoDisplay's recombinant mucins contain around 200 amino acids derived from human mucins (tandem repeat regions) and with 50-100 O-glycans with defined structures. 

Our recombinant human mucins have unique benefits compared to isolated animal mucins:

       - Distinct human mucins with human type O-glycans

       - Homogeneous molecules with tags

       - Glycans can be custom-designed to dissect functions

       - Mucins can be produced consistently in large scale

HEK 293 wild type cells are predicted to produce a mixture of ST, Disialyl T (DiST) and sialylated core2 O-glycan structures. GlycoDisplay apply gene enginerring technology (gene knock out (KO), knock in (KI), and activation (AC)) to generate O-glycoengineered HEK293 cell library that includes O-glycan structures with DiSialylT (DiST), SialylT (ST), Core1 (T), Tn and STn structure. 

Scientific publication:

Nason R, Bull C, Konstantinidi A, Sun L, Ye Z, Halim A, Du W, Sørensen DM, Durbesson F, Furukawa S, Mandel U, Joshi HJ, Dworkin LA, Hansen L, David L, Iverson TM, Bensing BA, Sullam PM, Varki A, Vries E, Haan C, Vincentelli R, Henrissat B, Vakhrushev S, Clausen H, Narimatsu Y (2021): Display of the human mucinome with defined O-glycans by gene engineered cells. Nat Commun, 1;12(1):4070. DOI: 10.1038/s41467-021-24366-4.