Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA; email:
Annu Rev Biochem. 2018 Jun 20;87:1-21. doi: 10.1146/annurev-biochem-062917-011911.
My initial research experience involved studying how bacteria synthesize nucleotide sugars, the donors for the formation of cell wall polysaccharides. During this time, I became aware that mammalian cells also have a surface coat of sugars and was intrigued as to whether these sugars might be arranged in specific sequences that function as information molecules in biologic processes. Thus began a long journey that has taken me from glycan structural analysis and determination of plant lectin-binding preferences to the biosynthesis of Asn-linked oligosaccharides and the mannose 6-phosphate (Man-6-P) lysosomal enzyme targeting pathway. The Man-6-P system represents an early example of a glycan serving as an information molecule in a fundamental cellular function. The remarkable advances in the field of glycobiology since I entered have uncovered scores of additional examples of oligosaccharide-lectin interactions mediating critical biologic processes. It has been a rewarding experience to participate in the efforts that have established a central role for glycans in biology.
我的初步研究经历涉及研究细菌如何合成核苷酸糖,这些糖是细胞壁多糖形成的供体。在这个过程中,我意识到哺乳动物细胞的表面也有一层糖,我很好奇这些糖是否可以排列成特定的序列,作为生物过程中的信息分子。就这样,我开始了一段漫长的旅程,从聚糖结构分析和确定植物凝集素的结合偏好,到 N-连接寡糖的生物合成和甘露糖 6-磷酸(Man-6-P)溶酶体酶靶向途径。Man-6-P 系统是糖作为基本细胞功能中信息分子的早期范例。自我涉足糖生物学领域以来,该领域取得了显著进展,发现了数十个糖-凝集素相互作用的其他例子,这些例子介导着关键的生物过程。能够参与到确立聚糖在生物学中的核心作用的研究中,是一件非常有意义的事情。