Our main research concerns the structure of granular starch and the fine structure of the molecular components of starch, especially amylopectin. We are also investigating the substitution pattern of chemically modified starches. We are using enzymatic methods in combination with chromatographic techniques.
There are two main projects: one deals with the role of polysialic acid in neural cell interactions, and the other with the role of carbohydrates as ligands for bacterial adhesion (Streptococcus pyogenes, Streptococcus suis).
Chiral ligands prepared from carbohydrates and useful in organic catalysis, have recently attracted a great deal of interest because of availability from nature at a reasonable price. An important advantage has also been that they make tedious optical resolution procedures unnecessary.The primary goal of the projects at TUT is to further improve the properties of carbohydrates useful as chiral ligands while varying the molecular structure.
We are mainly interested in leukocyte adhesion.Therefore we study the proteins ivolved, signal transduction and the role of carbohydrates. We are also interested in developing new analytical tools for cell surface carbohydrates. We work mainly with human cells.
We grow lactic acid bacteria, propionibacteria and bifidobacteria used in foodstuffs and screen to see if they produce extracellular polysaccharides (exopolysaccharides or EPS). The EPSs are separated and purified for NMR structural studies in Arrhenius Laboratory. In addition, some rheological studies of the EPSs have been carried out.
Our glycomics studies are focused on structural and immunochemical analysis of glycoconjugates and polysaccharides (e.g. polysialic acid, hyaluronate). We do also proteomics and mass spectrometry as well as structural and interaction studies of biomolecules using NMR.
Glycosylation of certain transmembrane proteins.
Use of cyclodextrins to improve pharmaceutical/biopharmaceutical properties of a drug molecule, in development of novel drug formulations and alternative administration routes. Development of novel derivatives of chitosan (biopolysaccharide) for drug delivery and formulation.
Glycosylation abnormalities in human cancers.
Changes in glycosylation in the models of Alzheimer's disease. We analyze the brain tissues from Alzheimer patients, from transgenic models of Alzheimer's disease and cultured neurons exposed to beta-amyloid, a 40-42 amino acid peptide is thought to be responsible for the development of this disease.
Hydrolysis, synthesis, binding and recognition of oligo- and polysaccharides; structure-function studies of fungal hydrolases and (mammalian) antibodies; directed evolution of polysaccharide degrading enzymes.
Pathogenic significance of bacterial adhesion to glycoconjugates (E. coli, Salmonella, Yersinia) and identification of of receptor-active molecules. Adhesion of commensal lactobacilli to host surfaces. Structure-function relationships in enterobacterial adhesion molecules.
Asymmetric chemical synthesis of natural and unnatural amino- and azasugars in enantiopure form.
Ongoing and planned work in the fields of synthetic and analytical
carbohydrate chemistry and bioorganometallics.
Mattias Roslund, Ph.D. student: glycolipids, glycoconjugates, synthetic
chemistry, NMR spectroscopy
Jonas Forsman, undergraduate: carbohydrate and bioorganometallic
chemistry
Preparation of glycoclusters, glycopeptides and oligonucleotide glycoconjugates. Mechanistic studies on glycosides.
NMR and advanced molecular modelling of protein - oligosaccharide interactions, oligosaccharide and polysaccharide structures and oligo- and polysaccharide modifying enzymes
Development of technology to produce mammalian glycosyltransferases in yeasts.
We aim to characterize the function of hydroxylysine and carbohydrates linked to hydroxylysine in proteins in vivo. We are now developing animal models for activity testing of the enzymes catalyzing these reactions (lysyl hydroxylase, glucosyltransferase).
Glykos operates and offers services in the fields of
Glycobiology
Structural and functional glycomics
Glycoenzymology
Carbohydrate chemistry
The work focuses mainly on heparan sulfate proteoglycans in brain development and plasticity.
A systems biology approach to inflammation role of glycoproteins.
Structural studies of polysaccharide degrading enzymes, xylose isomerase.
Glycoproteins in human plasma and blood cells.
Heparan sulfate, heparan sulfate proteoglycans, heparin-like polysaccharides: roles in growth factor signaling and cancer
Glycoforms dictate protein function. Differences in glycosylation and sperm-egg binding inhibition of glycodelin isoforms in female reproductive tissues.
Bacterial (genus yersinia) lipopolysaccharide genetics, biosynthesis and structure.
Hyaluronan function and regulation is studied in epithelial cells and tissues, particularly mammalian skin. According to the working hypothesis hyaluronan synthesis is required for keratinocyte stratification, and its synthesis rate regulates the number of vital epidermal cell layers, epidermal differentiation, and the healing of wounds. Models include human (HaCaT) and rat (REK) epidermal keratinocyte cell lines, primary mouse epidermal keratinocytes, an organotypic epidermis created from a continuous cell line, human epidermal organ culture, mouse skin in vivo and in organ culture, null mice for the hyaluronan receptor CD44, and cells derived from it.
We have found that hyaluronan concentration is an independent prognostic factor for an unfavourable outcome in colon, breast and ovarian cancer. Studies on the mechanism of hyaluronan action in cancer progression is underway.
Hemicelluloses are the second most abundant plant polysaccharides after cellulose. Our research is focusing on dietary fibre and on other applications of plant hemicelluloses. The research emphasizes the chemical analysis of hemicelluloses and their behaviour in different environments. Furthermore, new applications are explored for the more efficient utilization of hemicelluloses in different industrial fields. Enzymes are utilized in the stuctural analysis of hemicelluloses as well as in the targeted modification of hemicelluloses for the structure-function studies. We also study the production of specific oligosaccharides by enzymatic hydrolysis of hemicelluloses.
Protein engineering of industrial enzymes by rational design. Xylanases digest hemicellulosic xylan fibres and they are used in pulp bleaching and in improving the nutritive value of animal feed. Since 1998, we have studied the molecular determinants behind the thermostability and pH-dependent activity of xylanases. The research has produced an industrially relevant enzyme variant. Xylose isomerase is used industrially to produce fructose from glucose. We study by molecular simulations and site-directed mutagenesis the structural factors of enzyme catalysis. A goal of the research is to improve the reaction rate of xylose isomerase with non-natural substrates.
Interactions between cellulose and cellulose derivatives. Formation of linkages between wood polysaccharides and lignin. Conversion of reducing end groups of polysaccharides into aromatic end groups.