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Research project (§ 26 & § 27)
Duration : 2020-02-01 - 2024-01-31

Wider research context: Methylation of biomolecules plays an important role in many cellular regulation processes. For proteins and DNA, several methylating and de-methylating pathways are known. However, methyl groups are also found on glycan structures and for these, the modification mechanisms have not been investigated so far. Glycan structures play an important role in several recognition processes. Modifications on the sugar residues alter the specificity of attachment and binding events. Hypothesis/Objectives: In the current project we want to investigate the degradation of methylated glycan structures. Those organisms which are able to synthesise methylated glycans are expected to have also a mechanism to degrade these structures. Snail tissues have been shown to contain methyl groups on their protein linked glycans. Therefore they are candidates for enzymes which are able to degrade those structures metabolically. Approach: Demethylating enzyme activity of snail organelles will be determined using native and synthetic substrates. Proteins with the desired enzyme activity will be purified, sequenced, cloned and expressed. The native as well as the recombinant protein will be characterised for their biochemical and biophysical properties. Substrate specificities will be tested with native substrates as well as with other methylated molecules in order to get an overview on further potential applications. Sequence homology search will be performed in databanks of other organisms which are known to contain methylated sugar chains (other molluscs and parasites). Innovation: 1. A deeper knowledge regarding the methylation process may lead to an understanding of parasite-(intermediate) host interactions. 2. An enzyme which is able to cleave in a specific manner methyl groups from sugar residues will be a valuable tool in research as well as a candidate for applications in several disciplines.
Research project (§ 26 & § 27)
Duration : 2019-12-01 - 2023-11-30

Great advances have been made in recent years as regards genomic comparisons between organisms due to the large number of genome sequencing projects. In part these studies have altered our view of the phylogeny of organisms. However, the comparison of protein-linked carbohydrates, e.g., N-linked glycans, between organisms continues to lag behind due to the complicated nature of glycan analyses. On the other hand, glycans in their various types have key roles in fertilisation, development, morphogenesis and host-pathogen interactions as they cover the surfaces of all cells and so are involved in a wide range of cell-cell and self/non-self interactions In this project, it is proposed to focus on the N-linked glycans of selected bivalves, a group of predominantly marine organisms including oysters and clams – as a human food source, they have economic importance; on the other hand, as filter feeders they are of high ecological relevance. Furthermore, they harbour human pathogens, but are also susceptible to their own pathogens; invasive species (such as the pacific oyster, Crassostrea gigas) can be more resistant to these than the native bivalves. Glycans of bivalves representing different families and habitats (including the pacific oyster and clams) will be examined. The fine detail of the N-glycans of these organisms will be assessed by mass spectrometric and other analyses. Correlations between the loss or gain of carbohydrate epitopes will be made with genomic and lectin binding data; for the latter, a tailor-made array of glycans from different species and tissues will be developed and promises to drive forward our functional knowledge about the self/non-self recognition between lectins and glycans. The result of this study will be a deeper understanding of a group of key post-translational modifications in a class of organisms of environmental and economic importance and their contribution to self vs. non-self recognition as models for innate immunity.
Research project (§ 26 & § 27)
Duration : 2019-03-01 - 2023-02-28

The major aims of this project are related to galactose in Entamoeba histolytica in terms of its metabolism and incorporation into glycoconjugates, whereby galactose is a known component of the cell surface lipopeptidophosphoglycan (LPPG) as well as of N-glycans. However, other than the predicted occurrence of UDP-galactose epimerase, there is currently little information regarding galactose metabolic and transfer reactions in this parasite.

Supervised Theses and Dissertations