A few years later on the significance of this observation became clear when our lab, as well as the labs of Phil Robbins and Don Summers, showed that both high-mannose and complex-type glycans are derived from a common oligosaccharide of 14 sugars (three glucoses, nine mannoses, and twoN-acetyl glucosamines) that is transferred from a lipid-carrier to the nascent protein in the endoplasmic reticulum (ER) and then is processed in the ER and the Golgi to produce these two types of structures. glycosylation, that result from faulty glycan biosynthesis. == ESSAY == As an undergraduate student at Dartmouth College in the mid-1950s, I always looked forward to the yearly visit of the poet Cobalt phthalocyanine Robert Frost, a former student, who would go through his poetry to an enthralled target audience. One of my favorites was The Road Not Taken, which ends with the collection: Two roads diverged in a solid Cobalt phthalocyanine wood, and II required the one less traveled by, and that has made all the difference. Stuart Kornfeld ONCE I joined the field of glycobiology, there were only a handful of investigators working in this area. My first experience in this field was in the lab of Luis Glaser at Washington University or college where we showed that baker’s yeast contains a phosphomannomutase that converts mannose 6-phosphate (Man-6-P) to Man-1-P for the formation of GDP-mannose, a donor for mannan synthesis. I worked on this project during the summer time before I joined medical school, and while I found the experience thrilling, the topic seemed to have little relevance to medicine. I never imagined that 37 years later mutations in this enzyme would turn out to be the most common cause of a newly acknowledged group of genetic disorders termed Rabbit polyclonal to ALDH1A2 congenital disorders of glycosylation. It is a personal example of a well-established truth in science, that studies of simpler organisms often lead to major improvements in clinical medicine. During my time with Luis, I learned that most mammalian cells also contain a coat of sugar on their surfaces, termed the glycocalyx. There was little known about the structure or function of the molecules that comprise the glycocalyx, but it had been shown that one of the component sugars, sialic acid, served as a receptor for viral attachment. I also became aware of the work of Walter Morgan, Winifred Watkins, and Elvin Kabat showing that this ABO blood group determinants were carbohydrate in nature, with the A and B determinants differing by a single sugar that was selectively recognized by antibodies and herb lectins. This raised the possibility that the sugars in the glycocalyx might also be arranged in specific sequences to Cobalt phthalocyanine serve as information molecules in cellcell interactions. Energized by this possibility, I decided to take the road less traveled and enter the emerging field of glycobiology. After working several summers in the Glaser lab, I went to Victor Ginsburg’s lab at the NIH for two years to gain more experience in this area. It was an exciting time to be at the NIH, but one event was particularly important for my career. This was the start of my long-term scientific collaboration with my wife Rosalind, who experienced just received her Ph.D. in biochemistry, studying glycogen biosynthesis. As Joe Goldstein has eloquently pointed out, if you are fortunate to hook up with the right collaborator, the combined efforts of two minds can be a powerful force toward discovery. But he warned that one must be careful to choose a partner who is smarter than you (Goldstein and Brown, 2000). Certainly in my case I had formed the perfect partner. After two years at the NIH we were anxious to start our own lab and were fortunate to obtain faculty positions in the Department of Medicine at Washington University or college. One of the attractive features of the department was its strong support for the overall performance of basic research by its faculty. There was a acknowledgement that basic research ultimately propels improvements in clinical medicine. With the belief that knowledge of the structure of protein-linked oligosaccharides was fundamental for understanding the diversity and function of these molecules and for gaining insight into the enzymes involved in their synthesis, we set out to determine the structures of the N- and O-linked glycans of the monoclonal antibodies of patients with multiple myeloma as this provided large amounts of homogeneous glycoproteins synthesized by a single clone of plasma cells. As this work progressed and N-linked structures of other proteins became available, we noted a striking similarity of the core regions of high-mannose and complex-type glycans with each other and with the yeast mannan structures determined by Clint Ballou. A few years later the significance of this observation became obvious when our lab, as well as the labs of Phil Robbins and Don Summers, showed that both high-mannose and complex-type glycans are derived.