Glycomics Program

Tn-MUC1 in colonic cancer cell

Vision: to understand how glycans impinge on the biology of cells during tissue formation, inflammation, immunity and cancer growth, and how this can be exploited for early detection and treatment of disease.

Research focus: The glycome is considered the third language of life after the genome and the proteome. It comprises the myriad of sugars, also known as the complex carbohydrates, which cover the surface of our proteins and cells.Complex carbohydrates are essential for fundamental cellular functions, and changes to the glycome are often correlated with increased susceptibility to infection, metabolic disease and cancer. Additionally, hereditary defects in the glycome can cause a wide variety of symptoms such as cognitive impairment and developmental disability.

The Center aims to understand how changes in the glycome can cause or predict disease. Precise gene editing technologies such as ZFNs, TALENs and CRISPR/CAS9 are applied to regulate the expression of genes, which encode glycome-producing enzymes, and an array of advanced technologies are used to characterize the phenotype of the genetically modified cells.

Two strategic approaches have been developed to interrogate the functions of the glycome:

The SimpleCell strategy entails a systematic reduction of the complexity of the glycome by genetically simplifying the glycosylation in cells. The glycomes and glycoproteomes of modified cells are then mapped by mass spectrometry. This strategy has been successful in discovering new functions of glycosylation in diseases, and has even lead to discovery of new types of protein glycosylation.

The GlyMAP strategy uses a glycogenome approach to study the glycome by addressing all genes involved in glycosylation. Population exome data is explored for potential common deleterious glycogenes, and candidates are functionally validated for disease discovery.