Contact:

ao.Prof. DI Dr. Christina Schäffer

Keywords:

Carbodydrate engineering

Topic:

Glycosylation is the most prominent modification of naturally occurring S-layer proteins. Manipulation of S-layer glycosylation patterns by carbohydrate engineering techniques to create S-layer neoglycoproteins is adding a new dimension to the field of S-layer nanobiotechnolgy, especially when considering that about two thirds of all bioactive proteins are predicted to be glycoproteins.

The research unit “Nanoglycobiology” is dealing with molecular, genetic and regulatory details of the S-layer protein glycosylation pathway. Rational design of glycosylation motifs on S-layer proteins is being performed in homologous and heterologous bacterial and eukaryotic systems. Nanobiotechnology applications of tailored S-layer neoglycoproteins are based on the S-layer protein-inherent self-assembly properties and include the fields of receptor mimics, vaccine design, drug delivery using carbohydrate recognition as well as the fabrication of glycan nanoarrays.

The research focus is based on the specific manipulation of S-layer glycoproteins by protein and carbohydrate engineering techniques as well as on their self-assembly properties. One line of research utilizes homologous bacterial systems to achieve high-density, nano-scaled in vivo surface display of epitopes (e.g. immunogens). The in vitro line of development is directed towards surface display of immunogens on heterologous carriers such as liposomes, on the fabrication of versatile one-step reaction/detection nanoarray assays for quantification of analytes and of molecular interactions, and on the fabrication of enzyme nanoarrays. S-layer protein based supramolecular structures are exploited as innovative tools in the fields of nanobiotechnology, biomedicine, and food technology.

The practical relevance of research in the field of nanoglycobiology is based on the finding that glycosylated surface molecules may play pivotal roles in bacterial pathogenesis. In addition, biomedical research over the past years has shown that especially carbohydrates possess an enormous potential as lead structures for drug discovery. In this context, the periodontopathic organism Tannerella forsythia, whose glycosylated S-layer is postulated to be a virulence factor, is currently being investigated.

Publications (selected): 

  1. Sekot, G., Posch, G., Messner, P., Matejka, M., Rausch-Fan, X., Andrukhov, O., Schäffer, C. 2011. Potential of the Tannerella forsythia S-layer to delay the immune response. J. Dent. Res. 90, 109-114.
  2. Ristl, R., Steiner, K., Zarschler, K., Zayni, S., Messner, P., Schäffer, C. 2011. The S-layer glycome - adding to the sugar coat of bacteria. Int. J. Microbiol. 2011:127870.
  3. Zarschler, K., Janesch, B. Kainz, B., Ristl, R., Messner, P., Schäffer, C. 2010. Cell surface display of chimeric glycoproteins via the S-layer of Paenibacillus alvei. Carbohydr. Res. 345, 1422-1431.
  4. Zarschler, K., Janesch, B., Pabst, M., Altmann, F., Messner, P., Schäffer, C. 2010. Protein tyrosine O-glycosylation - a rather unexplored prokaryotic glycosylation system. Glycobiology 20, 787-798.
  5. Steiner, K., Hagelueken, G., Messner, P., Schäffer, C., Naismith, J.H. 2010. Structural basis of substrate binding in WsaF, a rhamnosyltransferase from Geobacillus stearothermophilus. J. Mol. Biol. 397, 436-447.
  6. Zarschler, K., Janesch, B., Zayni, S., Schäffer, C., Messner, P. 2009. Construction of a gene knockout system for application in Paenibacillus alvei CCM 2051T, exemplified by the S-layer glycan biosynthesis initiation enzyme WsfP. Appl. Environ. Microbiol. 75, 3077-3085.
  7. Thoden, J.B., Cook, P.D., Schäffer, C., Messner, P., Holden, H.M. 2009. Structural and functional studies of QdtC: an N-acetyltransferase required for the biosynthesis of dTDP-3-acetamido-3,6-dideoxy-alpha-D-glucose. Biochemistry 48, 2699-2709.
  8. Thoden, J.B., Schäffer, C., Messner, P., Holden, H.M. 2009. Structural analysis of QdtB, an aminotransferase required for the biosynthesis of dTDP-3-acetamido-3,6-dideoxy-alpha-D-glucose. Biochemistry 48, 1553-1561.
  9. Steiner, K., Hanreich, A., Kainz, B., Hitchen, P.G., Dell, A., Messner, P., Schäffer, C. 2008. Recombinant glycans on an S-layer self-assembly protein: a new dimension for nanopatterned biomaterials. Small 4, 1728-1740.
  10. Steiner, K., Novotny, R., Werz, D.B., Zarschler, K., Seeberger, P.H., Hofinger, A., Kosma, P., Schäffer, C., Messner, P. 2008. Molecular basis of S-layer glycoprotein glycan biosynthesis in Geobacillus stearothermophilus. J. Biol. Chem. 283, 21120-21133.
  11. Novotny, R., Berger, H., Schinko, T., Messner, P., Schäffer, C., Strauss, J. 2008. A temperature-sensitive expression system based on the G. stearothermophilus sgsE S-layer gene promoter. Biotechnol. Appl. Biochem. 49, 35-40.
  12. Schäffer, C., Novotny, R., Küpcü, S., Zayni, S., Scheberl, A., Friedmann, J., Sleytr, U.B., Messner, P. 2007. Novel types of biocatalysts based on the S-layer self-assembly system from Geobacillus stearothermophilus NRS 2004/3a, exemplified with the glucose-1-phosphate thymidylyltransferase RmlA: a nanobiotechnological approach. Small 3, 1549-1559.
  13. Steiner, K., Novotny, R., Patel, K., Vinogradov, E., Whitfield, C., Valvano, M. A., Messner, P., Schäffer, C. 2007. Functional characterization of the initiation enzyme of S-layer glycoprotein glycan biosynthesis in Geobacillus stearothermophilus NRS 2004/3a. J. Bacteriol. 189, 2590-2598.
  14. Zayni, S., Steiner, K., Pfoestl, A., Hofinger, A., Kosma, P., Schäffer, C., Messner, P. 2007. The dTDP-4-dehydro-6-deoxyglucose reductase encoding fcd gene is part of the surface layer glycoprotein glycosylation gene cluster of Geobacillus tepidamans GS5-97T. Glycobiology 17, 433-443.
  15. Steiner, K., Pohlentz, G., Dreisewerd, K., Berkenkamp, S., Messner, P., Peter-Katalinić, J. Schäffer, C. 2006. New insights into the glycosylation of the surface layer protein SgsE from Geobacillus stearothermophilus NRS 2004/3a. J. Bacteriol. 188, 7914-7921.

Collaborations:

Funding agencies:

  • FWF - Fonds zur Förderung der wissenschaftlichen Forschung, Wien