Background
Human glycobiology is a fascinating field of growing research that comprises investigations on all aspects of glycoconjugates such as functional mechanisms and structure determination. More and more biological functions of glycans are being discovered in diverse areas as brain and embryonic development, immune function, muscle extracellular matrix interactions, and many others. The essential roles of glycosylation are exemplified by i) the group of severe human genetic diseases, such as the dystroglycanopathies and the congenital disorders of glycosylation, ii) the impact on the activity and stability of recombinant therapeutical proteins and antibodies, and iii) the change of glycosylation patterns during numerous disease processes. Glycans are ubiquitously expressed in our whole body and several types of glycosylation can be distinguished. Glycans can be attached to lipids (glycolipids) or as a post-translational modification to proteins. Possible attachment sites include Asn (N-glycosylation), Ser, Thr or Hyl (O-glycosylation) or Trp (C-glycosylation). A distinction can be made between relatively short branched oligosaccharides on glycoproteins and longer unbranched polysaccharides (or glycosaminoglycans (GAGs)), on proteoglycans.
Figure depicting the subclasses of protein-linked carbohydrates (adapted from: Essential Glycobiology)
The advent of modern analytical tools, such as CE, HPLC and mass-spectrometry, has tremendously increased our knowledge of glycan structure-function relationships. Other methods, such as staining with lectins or glycan-specific antibodies, inhibition of glycosylation biosynthesis, etc. prove invaluable in the study of human glycobiology.
In the Nijmegen Glycobiology Platform (NGP), two groups are involved in the study of glycosaminoglycans. Matrix Biochemistry focuses on physiological and pathological aspects of GAGs in the extracellular matrix of various tissues. Hereto, GAG-specific single-chain antibodies were selected by Phage Display technology. The nephrology research group is interested in the role of GAGs in nephrological studies and has an interest in alfa-dystroglycan function. The organic synthesis group is interested in chemical synthesis, which provides the opportunity to create (non)-natural carbohydrate compounds for the study of and intervention in glycan specific interactions. Another focus in the NGP is on human genetic glycosylation disorders, either dystroglycanopathies or Congenital Disorders of Glycosylation (CDG). From a genetics perspective, homozygosity mapping, data mining and molecular biological tools are employed to elucidate glycogenes that are responsible for new genetic disorders. In the CDG group, research is focused on the development of biochemical and analytical tools to investigate glycosylation abnormalities in genetic diseases. More information can be found in the description of the respective groups.