The division of Matrix Biochemistry studies protein sugar molecules that control cell behaviour, with focus on so-called proteoglycan. The aim is to clarify the underlying mechnisms of diseases of kidneys, muscles and lungs in particular.
A holistic approach has been adopted, combining molecular biological, biochemical, cell biological and morphological methods. Multidisciplinary research is also being carried out into methods for (re-)generating tissues and organs within or outside the body ('tissue engineering').
The major lines of research are:
- Matrix molecules
- Tissue engineering
- Human muscle
All three topics are interrelated, and contain elements of basic research, pathophysiology, and biomedical application.
Matrix molecules
The main focus of this part of research will be on heparan sulfate proteoglycans, particularly on the polysaccharide chains (heparan sulfates, HS). HS are long polyanionic polysaccharides consisting of 100--150 disaccharides. Due to extensive modifications, a large potential for different HS species and domains exist. HS bind and modulate a myriad of proteins including growth factors/cytokines, enzymes, protease inhibitors and viral and bacterial proteins. They function as depots and/or co-receptors for a large set of growth factors. Cells may create their microenvironment by expressing specific HS sequences on the cell surface and in the extracellular matrix.
Major research themes are:
- determination of the monosaccharide sequences of HS species
- assignment of biological function to specific sequences
- study of disease-related alterations in HS sequences using phage display-derived antibodies, and focussing on tumor formation, and renal and pulmonary pathology
- application of anti-HS antibodies for diagnostics, and use of sequence information for rational design of therapeutic glycomimetica
Tissue enigineering
As much as cells signal to their environment, the environment signals to the cells. Extracellular matrix molecules and growth factors play an important role in this respect. The main goal of this part of research is to engineer bioscaffolds which provide appropriate signals to cells for proliferation/differentiation, and which induce the formation of new tissues/organs (tissue engineering).
Major research themes are:
- development of organ/tissue specific biomatrices based on matrix molecules (e.g. collagens, glycosaminoglycans, elastin) and growth factors (e.g. FGFs, VEGF)
- evaluation of tissue (re)generation capacity of biomatrices in vitro and in vivo (target organs will be skin, cartilage, blood vessels and skeletal muscle)
Human muscle
Exitation and contraction of skeletal muscle are highly dependent on the presence, location, and functioning of ion channels/pumps. The aim of this part of research is to elucidate the mechanism of clustering and functioning of ion channels in normal and pathological muscle and in cultured muscle cells.
Major research themes are:
- the influence of cell surface glycosaminoglycans on the clustering and functioning of ion channels (acetylcholine receptor, voltage dependent Na+-channel, dihydropyridine and ryanodine receptors)
- the role of ion channels/pumps in various myopathies (e.g. Brody's disease, malignant hyperthermia, myotonic dystrophy, ion channel diseases)
- the importance of cell surface heparan sulfates in formation and functioning of the neuromuscular junction, studied in mice knock-out for heparan sulfate species, and which are generated by expression of anti-HS antibodies ("knocking out by knocking in").