Investigations Into the Regulation of Plasticity of O-Linked Glycosylation and its Functional Significance

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Glycosylation is a co-ordinated process where single sugars or sugar chains, called glycans, are added to proteins by enzymes to form glycoproteins. It is an important and abundant form of protein modification and approximately half of all proteins in humans are glycosylated. There are various types of glycosylation however, this project will focus on O-linked glycosylation. The most common form of O-linked glycosylation is initiated by the addition of a sugar residue called N-acetylgalactosamine (GalNAc) to either a Serine (Ser) or Threonine (Thr) amino acid within a protein, to form the Tn antigen. In normal healthy cells this initial structure is then further elaborated to form eight core structures. When alterations in O-linked glycosylation occur, such as failure in O-glycan chain extension it exposes the usually cryptic Tn antigen. The surface of cells are decorated with O-linked glycoproteins which are implicit in essential biological functions, these range from metabolic to structural and physical functions. Despite this biological significance, the O-linked glycosylation repertoire of a cell, itsfunctionality and the factors regulating it are still poorly understood. This project will therefore investigate the regulation of plasticity demonstrated in O-linked glycans by exploring and manipulating potential underlying regulatory mechanisms. It will also investigate the functional significance of this plasticity by exploring the relationship between O-linked glycosylation status and functionality in processes such as cell-cell adhesion, cell invasion and cell migratory capability.