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

糖基化是一个协调的过程，在这个过程中，单糖或糖链，被称为多糖，通过酶添加到蛋白质上形成糖蛋白。它是一种重要而丰富的蛋白质修饰形式，人类体内约有一半的蛋白质是糖基化的。糖基化有多种类型，但本项目将重点放在O-连接的糖基化上。最常见的O-连接糖基化形式是将名为N-乙酰半乳糖胺(GalNAc)的糖残基添加到蛋白质中的丝氨酸(Ser)或苏氨酸(Thr)氨基酸中，形成TN抗原。在正常的健康细胞中，这个初始结构随后被进一步细化，形成八个核心结构。当O-连接的糖基化发生改变时，例如O-糖链延伸失败，它暴露出通常隐蔽的Tn抗原。细胞表面装饰着O-连接的糖蛋白，这些蛋白隐含在基本的生物功能中，这些功能从代谢到结构和物理功能都有。尽管有这样的生物学意义，但对细胞的O-连接糖基化反应、其功能和调节因素仍知之甚少。因此，该项目将通过探索和操纵潜在的潜在调控机制来研究O-连接多糖中所展示的可塑性的调控。它还将通过探索细胞-细胞黏附、细胞侵袭和细胞迁移能力等过程中O-连接糖基化状态与功能的关系来探讨这种可塑性的功能意义。

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.