Every human cell is covered by a dense layer of glycans, chains of sugar molecules linked to each other in a combinatorial manner thereby forming short, long, linear, and branched structures. The biosynthesis of glycans takes place in the endoplasmic reticulum and Golgi system by more than 200 glycosyltransferase enzymes that build the diverse glycans that are attached to membrane or secreted glycoproteins and glycolipids. Glycans are frequently terminated by sialic acids that are a family of chemically diverse sugars that can be linked to underlying sugars via different chemical bonds. This process in carried out by 20 sialyltransferase isoenzymes with partially overlapping functions that are not fully elucidated. Due to this combinatorial diversity, human cells produce a vast repertoire of structurally diverse sialic acid-carrying glycans (sialoglycans) at the surface - the Sialome. The Sialome is involved in numerous molecular interactions at the cell surface and biological processes such as cell-cell interactions and cell-extracellular matrix interactions. The Sialome constitute the ligands for sialoglycan-binding proteins such as the Selectins and the Siglec immune receptor family that have regulatory functions in the immune system. Pathogens exploit the Sialome to infect host cells and aberrations in the Sialome have been associated with inflammation, autoimmunity, and cancer. For example, cancer cells are frequently found to present aberrant sialoglycans that are associated with tumor growth and progression. Dissection of the biological interactions with the Sialome could provide insights into these physiological and pathological processes providing novel opportunities for the development of therapeutic approaches targeting the Sialome in major diseases such as infection, autoimmunity, and cancer. So far, the field has mainly focused on developing analysis techniques for sialoglycans in biological samples and their chemical synthesis. However, research into the biological interactions and functions of the Sialome in health and disease is rather limited, because suitable methods to address the Sialome as well as specific sialoglycans in the natural context of the cell surface are lacking. The aim of this project was to develop a cell-based sialoglycan array for display of the Sialome in the natural glycan context of glycoconjugates and the cell membrane suitable for cell-based assays and dissection of the biological interactions with sialoglycan-binding proteins such as the Siglecs.
