Research conducted by the Laboratory of Nematology is part of the research program of the Graduate School Experimental Plant Sciences (EPS) and the C.T. de Wit Graduate School for Production Ecology & Resource Conservation (PE&RC).
Parasitic worm (helminth) infections still have a major impact on health of humans and animals. Mass drug administration are used to treat helminth infections, however, these are not always effective and cases of drug resistance are reported. Therefore, we aim to develop a more sustainable solution: a recombinant vaccine.
Components released by the helminth during infection interact with the immune system of the host and are therefore considered as potential vaccine candidate. Many of these released components are unique glycoproteins, which carry different glycosylation patterns. Obtaining the correct glycosylation is important for stability and efficacy of a potential vaccine.
To investigate potential vaccine candidates, Nicotiana benthamiana plants are used as production platform. By adapting the post-translational machinery of the plant, specific sugar motifs can be introduced or deleted to obtain the correct glycan composition of the vaccine.
Phosphorylcholine (PC) is one of the unique sugar motifs found on glycoproteins of filarial helminths (e.g. Brugia malayi). PC is involved in the immunomodulatory strategy of the helminth, enhancing the lifespan of the worm and reduce pathology in the host. Implementing PC into plant-produced glycoproteins is not yet possible, since the glycosyltransferase responsible for the attachment of PC to the glycan is unknown. It is proposed that fukutin-related genes are involved in the transfer of PC. In this research, I will study the PC-glycan synthesis in model nematode C. elegans, to further understand the biosynthetic pathways leading to PC-glycan synthesis. Subsequently, these findings will be implemented in the plant glycosylation platform to produce recombinant PC-containing helminth glycoproteins.