Studies of the O-GlcNAc Modification

人类基因组测序揭示了一个可怕的现象。从表面上看，人类一点也不复杂：只有20- 25000个基因。然而，我们都知道，人类是复杂的有机体。这种复杂性部分源于我们细胞内发生的化学反应，这些化学反应扩大了蛋白质的复杂性，蛋白质是这2万个基因的产物。细胞内可能发生的最重要的修饰之一是蛋白质与一种叫做n -乙酰氨基葡萄糖的糖基化。这是一种动态修改：糖可以根据不同的刺激，包括饮食、激素等，增加和减少。这些修饰也非常重要，因为它控制着健康细胞的功能。此外，缺失的修饰状态与癌症和糖尿病等疾病有关。本基金提出的研究旨在了解这种n -乙酰氨基葡萄糖修饰的化学和生物化学。这将使研究人员能够探索健康细胞的生物学，也允许设计和利用化学分子来告知我们疾病过程的知识。

The sequencing of the human genome revealed a frightening observation. On the face of it, humans are not very complex at all: only 20-25,000 genes. Yet, as we all know, humans ARE complex organisms. This complexity is derived, in part, from chemical events that take place withing our cells which serves to expand the complexity of proteins - the products of these these 20,000 genes. One of the most important modifications that can take place withing cells is glycosylation of proteins with a sugar called N-acetylglucosamine. This is a dynamic modification: sugars can be put on and taken off in response to diverse stimuli including diet, hormones etc. These modifications are also very important in that it controls the function of the healthy cell. Furthermore, aberent states of modifications are linked to diseases such as cancer, and diabetes. The research proposed in this grant seeks to understand the chemistry and biochemistry of this N-acetylglucosamine modification. This will allow researchers to probe the biology of the healthy cell and also allow the design and exploitation of chemical molecules to inform our knowledge of disease processes.