IMass Time: The Future, in Future!

Joseph John Thomson discovered and proved the existence of electrons through a series of experiments. His work earned him a Nobel Prize in 1906 and initiated the era of mass spectrometry (MS). In the intervening time, other researchers have also been awarded the Nobel Prize for significant advances in MS technology. The development of soft ionization techniques was central to the application of MS to large biological molecules and led to an unprecedented interest in the study of biomolecules such as proteins (proteomics), metabolites (metabolomics), carbohydrates (glycomics), and lipids (lipidomics), allowing a better understanding of the molecular underpinnings of health and disease. The interest in large molecules drove improvements in MS resolution and now the challenge is in data deconvolution, intelligent exploitation of heterogeneous data, and interpretation, all of which can be ameliorated with a proposed IMass technology. We define IMass as a combination of MS and artificial intelligence, with each performing a specific role. IMass will offer advantages such as improving speed, sensitivity, and analyses of large data that are presently not possible with MS alone. In this study, we present an overview of the MS considering historical perspectives and applications, challenges, as well as insightful highlights of IMass.

A Lifetime of Adventures in Glycobiology.

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.

Werner Reutter: A Visionary Pioneer in Molecular Glycobiology.

A creative pioneer: Werner Reutter (1937-2016) was a scientist who both made fundamental discoveries in glycobiology and reached out to disciplines beyond his core field. Many of his former colleagues and students will remember his desire to exchange research ideas, which ultimately contributed to the birth of new research fields.

Fulfilling Koch's postulates in glycoscience: HCELL, GPS and translational glycobiology.

Glycoscience-based research that is performed expressly to address medical necessity and improve patient outcomes is called "translational glycobiology". In the 19th century, Robert Koch proposed a set of postulates to rigorously establish causality in microbial pathogenesis, and these postulates can be reshaped to guide knowledge into how naturally-expressed glycoconjugates direct molecular processes critical to human well-being. Studies in the 1990s indicated that E-selectin, an endothelial lectin that binds sialofucosylated carbohydrate determinants, is constitutively expressed on marrow microvessels, and investigations in my laboratory indicated that human hematopoietic stem cells (HSCs) uniquely express high levels of a specialized glycoform of CD44 called "hematopoietic cell E-/L-selectin ligand" (HCELL) that functions as a highly potent E-selectin ligand. To assess the role of HCELL in directing HSC migration to marrow, a method called "glycosyltransferase-programmed stereosubstitution" (GPS) was developed to custom-modify CD44 glycans to enforce HCELL expression on viable cell surfaces. Human mesenchymal stem cells (MSCs) are devoid of E-selectin ligands, but GPS-based glycoengineering of CD44 on MSCs licenses homing of these cells to marrow in vivo, providing direct evidence that HCELL serves as a "bone marrow homing receptor". This review will discuss the molecular basis of cell migration in historical context, will describe the discovery of HCELL and its function as the bone marrow homing receptor, and will inform on how glycoengineering of CD44 serves as a model for adapting Koch's postulates to elucidate the key roles that glycoconjugates play in human biology and for realizing the immense impact of translational glycobiology in clinical medicine.

[Glycotechnology in China].

Glycotechnology is a new branch of biotechnology, emerged early 1990's. In this article, the international background of glycotechnology is briefly introduced and history of glycotechnology in China is reviewed.

History of plant lectin research.

Numerous plant species are known to express one or more lectins or proteins containing a lectin domain, enabling these proteins to select and bind specific carbohydrate structures. The group of plant lectins is quite heterogeneous since lectins differ in their molecular structure, specificity for certain carbohydrate structures, and biological activities resulting therefrom. This chapter presents a short historical overview on how plant lectin research has evolved over the years from a discipline aiming merely at the purification and characterization of plant lectins towards the application of plant lectins as tools in glycobiology.