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Research project (§ 26 & § 27)
Duration : 2017-03-01 - 2019-02-28

Aim of the project between EGGER and BOKU is to develop a binder for wood based on lignin, isolated from black liquor, a waste stream of the pulp and paper industry. The project will search for appropriate methods to provide isolated lignin. In a subsequent step the lignin will be comprehensively characterized based on methods developed at the Department of Chemistry, Division of Chemistry of Sustainable Resources.
Research project (§ 26 & § 27)
Duration : 2016-06-01 - 2019-05-31

Recognition of the endotoxic portion of the Gram-negative bacterial lipopolysaccharide (LPS), a glycophospholipid Lipid A, by the transmembrane protein complex Toll-like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD-2) and by the intracellular serine protease Caspase-4/11 initiates activation of the pro-inflammatory signaling cascade and is essential for the control of infectious diseases. Activation of TLR4 was also shown to bridge the innate and adaptive immunity, which highlights stimulation of TLR4 complex by the non-pyrogenic ligands as a useful approach for development of novel vaccine adjuvants. Though, LPS-induced TLR4 signaling may result in the development of a dysregulated innate immune response leading to variety of inflammatory conditions. To explore the molecular basis for Lipid A – induced Caspase-4/11 (non-canonical TLR4-independent inflammasome activation) and TLR4 activation, chemical synthesis and immuno-functional studies of innovative conformationally confined Lipid A mimetics is intended. Lipid A is composed of a 1,4′ -bisphosphorylated βGlcN(1→6)GlcN polar head group which carries a variable number of long-chain (R)-3-hydroxyacyl- and (R)-3-acyloxyacyl residues in symmetric or asymmetric distribution. Synthesis of Lipid A mimetics wherein the flexible three-bond β(1→6) connection is exchanged for a rigid two-bond β,β-(1↔1) glycosidic linkage will provide potentially agonistic Caspase-4/11 and TLR4 ligands. Restricting conformational flexibility of Lipid A by fixing the molecular shape of its carbohydrate backbone in a predefined conformation attained by a rigid β,β-(1↔1)-linked disaccharide scaffold would allow to attain a specific topology of the functional groups of the ligands (phosphates and long-chain (R)-3-acyloxyacyl residues) in the ligand-protein complexes. Evaluation of the tetriary structure of the ligand in respect to its immuno-stimulating activity will ensure a reliable correlation of structure-activity relationships.
Research project (§ 26 & § 27)
Duration : 2017-07-01 - 2021-06-30

Haemonchus contortus is one of the major helminthic parasites, which infects sheep and goats resulting in economic loss of the ruminant industry worldwide. In comparison to the usage of anthelmintic reagents which can cause resistance among parasitic nematodes, vaccination represents a sustainable and effective approach. Vaccination with a mixture of native Haemonchus gut glycoproteins (namely H11 antigens) has shown effective protection in lambs. However, attempts to produce these antigens recombinantly in various expression hosts and use them as vaccines resulted in either low or no protection in animal trials. As the native H11 antigens are known to carry additional modifications with sugars on the surface of proteins (termed “glycosylation”), which plays an important role in the biological function of antigens, investigation on how to mimic these natural sugar modifications on the recombinant H11 became necessary and will facilitate the production of effective antigens. The sugar structures on the native H11 antigens possess a special “core” modified with up to three fucose residues, which are enzymatically synthesised by three fucosyltransferases. A commercial insect cell line (Hi5) is a suitable host for glycoengineering using recombinant baculovirus to introduce genes encoding Caenorhabditis elegans glyco-enzymes, which can be used to effectively remodel the sugars on the selected helminth reporter. Full length nematode glyco-enzyme encoding sequences are sufficient for Golgi targeting and realising glycoengineering in insect cells. The biological role of C. elegans glyco-enzymes will be investigated by studying the N-glycomes of relevant mutants using HPLC and mass spectrometers as major tools. Recombinant baculoviruses carrying genes encoding two C. elegans glyco-enzymes and DNA sequences encoding Haemonchus H11 (expression targets) will be prepared using molecular biology approaches to produce H11 antigens in Hi5 insect cells. In addition to the protein sequences and peptidase activities, the biochemical properties of glyco-engineered H11 antigens will be evaluated focusing on the sugar modifications and other potential protein modifications. This is probably the first attempt to express helminth antigens modified with authentic sugars in insect cells. The glyco-engineered recombinant H11 antigens are expected to better mimic the native H11 antigens; therefore they may serve as a vaccine candidate in animal trials to protect ruminants from Haemonchus infection.

Supervised Theses and Dissertations