Glycomic studies of parasitic nematodes
File(s)
Author(s)
Sutov, Grigorij
Type
Thesis
Abstract
Haemonchus contortus and Dictyocaulus viviparus are parasitic nematodes which infect small ruminants and cattle, respectively worldwide causing huge economic losses. The current major control method is the usage of anthelmintic drugs. However, increasingly this strategy is failing due to an increase in parasite drug resistance. New control methods are therefore urgently needed and an attractive potential choice would be vaccination. However, all the attempts to create recombinant vaccines to date have failed therefore a potentially novel approach would be the development of carbohydrate-based vaccines. One of the major bottlenecks in this approach is the lack of structurally characterized parasitic nematode glycans.
In this thesis mass-spectrometry-based structural glycomic characterization of protein linked N- and O-glycans from Haemonchus contortus and Dictyocaulus viviparus adult and L3 stage parasites has been performed. The adult Haemonchus contortus glycomic analysis revealed previously unseen Gal-Fuc structures present in both N- and O-glycans. None of these structures were detected in L3 stage N- and O-glycan analysis. In comparison phosphorylated Galβ1-3(Galβ1-6)-GalNAc Core O-glycans were observed. The O-glycan analysis of L3 stage Dictyocaulus viviparus revealed the presence of Galβ1-3(Galβ1-6)-GalNAc Core glycans which can be further modified with fucose and α/β-galactoses. In contrast to L3 stage, the adult O-glycan analysis reveals mainly Core-2 based structures with the highest molecular weight structure forming the Lewisx antenna which is also abundantly observed in adult N-glycans.
In this thesis mass-spectrometry-based structural glycomic characterization of protein linked N- and O-glycans from Haemonchus contortus and Dictyocaulus viviparus adult and L3 stage parasites has been performed. The adult Haemonchus contortus glycomic analysis revealed previously unseen Gal-Fuc structures present in both N- and O-glycans. None of these structures were detected in L3 stage N- and O-glycan analysis. In comparison phosphorylated Galβ1-3(Galβ1-6)-GalNAc Core O-glycans were observed. The O-glycan analysis of L3 stage Dictyocaulus viviparus revealed the presence of Galβ1-3(Galβ1-6)-GalNAc Core glycans which can be further modified with fucose and α/β-galactoses. In contrast to L3 stage, the adult O-glycan analysis reveals mainly Core-2 based structures with the highest molecular weight structure forming the Lewisx antenna which is also abundantly observed in adult N-glycans.
Version
Open Access
Date Issued
2015-09
Date Awarded
2016-01
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Haslam, Stuart
Dell, Anne
Sponsor
Biotechnology and Biological Sciences Research Council
Publisher Department
Life Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)