Dorothe Spillmann research group

The connection between out- and inside of a cell – can glycosaminoglycans tune cellular control?

Our group is interested to elucidate how glycosaminoglycans (GAGs) participate in cellular activities important in physiology and pathology. In multicellular organisms these carbohydrates are ubiquitously expressed in a tissue specific manner at cell surfaces and in extracellular matrices. But why all energy is invested for their controlled synthesis is an enigma. A potential explanation may be found in the interplay between a large number of different proteins important during embryogenesis, development and homeostasis and such GAG chains. When altered in either appearance or structure these chains can then also be part of pathologic changes. Our working hypothesis is that GAGs play an important function in an organism to help create and maintain a robust cellular interplay during tissue development and homeostasis. A correct functioning requires that cell-cell communication must be well tuned but also buffered to some extend. This would require prompt adaptation to changed needs but also stability in the system to cope with a certain level of ‘browse’ in form of defects or suboptimal performance of different players. We envision heparan sulfate (HS) and chondroitin sulfates (CS) as tuning molecules to play at cell surfaces with consequence for cellular signaling properties and thus cellular fate. To approach our hypotheses we correlate structural features in different physiological and pathological conditions with functional properties on one hand and on the other hand we deliberately modulate the expression of these carbohydrates in model systems to check the influence of qualitative and quantitative changes on target properties. Thus, our goals are to elucidate the underlying mechanisms how HS and CS structures modulate cellular behavior and communication, of critical importance for physiological and pathological processes.

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