The goal is to characterise the biological roles cell surface glycoconjugates focusing on the molecular mechanisms of the interactions of carbohydrates with their ligands. The main topics are the role of carbohydrates like polysialic acid in neural cell interactions, and the adhesion of bacteria to host cells. Polysialic acid is a neurodevelopmental carbohydrate antigen shared by the neural cell adhesion molecule NCAM and the capsular polysaccharides of meningitis-causing bacteria. It appears to regulate cell interactions in neural tissue. Its role in the pathogenesis of meningitis is not known. We aim at revealing the role of polysialic acid in normal neural tissue and pathological situations like stroke and neural tumours, as well as the development of meningitis. On the other hand meningitis-causing and other pathogenic bacteria attach to their tissue receptors by the binding of their adhesin molecules to specific sugar ligands on cell surfaces. Characterisation of these molecular interactions sheds light into the pathogenic mechanisms of bacterial diseases, and also enables the development of new vaccines and new types of drugs that interfere with bacterial adhesion. We use libraries of carbohydrates, synthetic inhibitors, enzymes and recombinant proteins to identify and characterise carbohydrate-binding proteins and determine their interaction mechanisms by X-ray crystallography and NMR. A recent focus of our interests has also been the hydrogen peroxide resistance protein Dpr, which also shows carbohydrate-binding activity.

• Role of polysialic acid in regeneration and tumour development
• Mechanism of enzymatic catalysis by endosialidase
• Inhibitors polysialic acid biosynthesis
• Crystal structure of Streptococcus suis adhesin-ligand complex
• Novel vaccines for S. suis, S. pneumoniae and S. pyogenes
• Mechanisms of hydrogen peroxide resistance in gram-positive pathogens

• Pulliainen, AT, Kauko, A, Haataja, S, Papageorgiou, AC, Finne, J. Dpr/Dps ferritin-like protein: insights into mechanism of iron incorporation and evidence for a central role in cellular iron homeostasis in Streptococcus suis. Mol Microbiol 2005; 57: 1086-1100.
  
  PubMed - abstract

• Loimaranta, V, Jakubovics, NS., Hytönen, J, Finne J, Jenkinson, HF, Strömberg, N. Fluid- or surface-phase human salivary scavenger protein gp340 exposes different bacterial recognition properties. Infect Immun 2005; 73: 2245-2252.
  
  PubMed - abstract

• Jokilammi, A, Ollikka, P, Korja, M, Jakobsson, E, Loimaranta, V, Haataja, S, Hirvonen, H, Finne, J. Construction of antibody mimics from a noncatalytic enzyme-detection of polysialic acid. J Immunol Methods 2004; 295: 149-160.
  
  PubMed - abstract

• Kauko, A, Haataja, S, Pulliainen, AT., Finne, J, Papageorgiou, AC. Crystal structure of Streptococcus suis Dps-like peroxide resistance protein Dpr: Implications for iron incorporation. J Mol Biol 2004: 338, 547-558.
  
  PubMed - abstract

• Pulliainen, AT., Haataja, S, Kähkönen, S, Finne, J. Molecular basis of H2O2 resistance mediated by streptococcal Dpr. Demonstration of the functional involvement of the putative ferroxidase center by site-directed mutagenesis in Streptococcus suis. J Biol Chem 2003; 278: 7996-8005.
  
  PubMed - abstract

• Hytönen, J, Haataja, S, Finne, J. Streptococcus pyogenes glycoprotein-binding strepadhesin activity is mediated by a surface-associated carbohydrate-degrading enzyme, pullulanase. Infect Immun 2003; 71: 784-793.
  
  PubMed - abstract

• Häyrinen, J, Haseley, S, Talaga, P, Mühlenhoff, M, Finne, J, Vliegenthart, JFG. High affinity binding of long-chain polysialic acid to antibody, and modulation by divalent cations and polyamines. Mol Immunol 2002; 39: 399-411.
  
  PubMed - abstract

• Aalto, J, Pelkonen, S, Kalimo, H and Finne, J. Mutant bacteriophage with non-catalytic endosialidase binds to both bacterial and eukaryotic polysialic acid and can be used as probe for its detection. Glycoconjugate J 2001; 18: 751-758.
  
  PubMed - abstract

• Hytönen, J, Haataja, S, Gerlach, D, Podbielski, A and Finne, J. The SpeB virulence factor of Streptococcus pyogenes, a multifunctional secreted and cell surface molecule with strepadhesin, laminin-binding and cysteine protease activity. Mol. Microbiol. 2001; 39: 512-519.
  
  PubMed - abstract

• Hytönen, J, Haataja, H, Isomäki, P, Finne, J. Identification of a novel glycoprotein-binding activity in Streptococcus pyogenes regulated by the mga gene. Microbiology 2000; 146: 31-39
  
  PubMed - abstract

• Haataja, S, Zhang, Z, Magnusson, G, Finne, J. Determination of the cell adhesion specificity of Streptococcus suis with the complete set of monodeoxy analogues of globotriose. Glycoconjugate J 1999; 16: 67-71
  
  PubMed - abstract

• Toikka, J, Aalto, J, Häyrinen, J, Pelliniemi, LJ, Finne, J. The polysialic acid units of the neural cell adhesion molecule N-CAM form filament bundle networks. J Biol Chem 1998; 273: 28557-28559
  
  PubMed - abstract

• Hansen, HC, Haataja, S, Finne, J, Magnusson, G. Di-, tri-, and tetravalent dendritic galabiosides that inhibit hemagglutination by Streptococcus suis at nanomolar concentration. J Am Chem Soc 1997; 119: 6974-6979
  
  Abstract

  

Doctoral Theses

• Binding mechanism of Streptococcus suis to host cell surface carbohydrates. Sauli Haataja, 1996

• Capsular polysaccharides of bacteria causing meningitis. Antibody-binding properties and cross-reactivity with tissue glycoproteins. Jukka Häyrinen, 1996

• Purification and properties of a galactosyl-a1-4-galactose-binding adhesin - a potential vaccine against Streptococcus suis. Kaarina Tikkanen, 1996

• Characterization of Pectinatus cerevisiiphilus and P. frisingiensis surface components. Use of synthetic peptides in the detection of some of gram-negative bacteria. Elias Hakalehto, 2000.

• Group A streptococcal strepadhesin activity. A glycoprotein-binding activity mediated by cysteine protease and pullulanase. Jukka Hytönen, 2003