Research Fellows Directory
Maria Carmen Galan
Dr Maria Carmen Galan
University of Bristol
The gastrointestinal tract possesses a protective epithelial barrier as part of the basic innate protective system, which produces a secreted mucus layer that acts as physical barrier against pathogenic invasion. The molecules which give the mucus layer its characteristic sticky, viscoelastic properties are the mucins, which are sugar rich proteins of very high molecular weight that are able to form gels and generate the mucus layer and barrier. The mucins contain hundreds of different mucin-type, O-linked oligosaccharides and it has been observed that expression of certain types of O-glycans are linked to diseases such as inflammatory bowel disease, cystic fibrosis and different types of cancer. Despite their importance, little is known about the role and distribution of mucins in the different regions of the human intestine in both healthy and diseased states. In recent years, some mucin oligosaccharide structures found distributed throughout the intestinal tract have been identified. However, none of these structures are available in significant amounts or purity for biological studies. Consequently, the synthesis of defined mucin-type oligosaccharide fragments will be critical to help us understand their biological and disease implications.
Access to structurally defined complex carbohydrates is still a very laborious process that requires a high level of technical expertise, often carried out by a small number of specialized laboratories, thus combinatorial approaches to prepare diverse libraries of oligosaccharides remain limited. A general, automated method for oligosaccharide assembly will allow rapid preparation of structures of interest and will enhance not only glycobiology research, but also carbohydrate-based drug discovery. The proposed programme aims to develop a new methodology for the general synthesis and rapid purification of oligosaccharides. The technique is based on ionic pair interactions between an immobilized carbohydrate (ITagged) and the appropriate solvent, that would enable “catch and release” of the required product at each step, simplifying greatly the purification. It is hoped that this approach will be applicable to the automated synthesis of complex oligosaccharide structures.