The overall aim of the research is to develop intervention tools and strategies against parasitic infections and inflammatory diseases using glycobiological approaches.
A main cross-cutting research line in the Department of Parasitology aims to understand the key roles that glycans plays in host-pathogen interactions, with a special interest in schistosomiasis and other parasitic helminth infections.
All organisms - host or pathogen - express carbohydrate chains (glycans) on glycoproteins and glycolipids on the cell surface and in secretions. This glycosylation is highly diverse and dynamic. In the context of host-pathogen interaction many pathogen-derived glycans are antigenic, giving rise to antibodies and triggering innate and adaptive cellular immune responses. Parasitic helminth express a variety of immunogenic glycans that are crucial to establishing or maintaining infection of the host by the mediating or modulating immunity. These properties are an ideal basis for glycans to be explored and exploited for the development of vaccines, immuno-therapeutics and diagnostics.
The main glycobiology research themes & technologies are:
- The use of glycomics approaches based on mass spectrometry and glycan-microarrays for the identification of helminth glycan targets for diagnostics and vaccines
- Structure-function studies of native and recombinant helminth glycoproteins as immunomodulators
- Functional analysis of schistosome glycosylation in vitro and in vivo using chemical and genetic tools.
Glycomics approaches for the identification of glycan targets
Applying state-of-the-art glycomics technologies including mass spectrometry and glycan microarrays constructed of native or synthetic glycan antigens we study in detail the glycosylation of schistosomes and other medical or socioeconomically important helminths. By screening antibodies in sera from endemic populations, from infected animals, or from our controlled human infection studies, we identify antigens that are subsequently explored as diagnostic targets or as glycan-based vaccines in rodent models.
Structure-function studies of immunomodulatory helminth glycoproteins
Helminths are masters in modulating the immune response of their host in order to establish long term survival. The immunoregulatory responses that helminths induce have beneficial effects on the development of allergic disorders and type 2 diabetes. At the molecular level, glycobiological mechanisms play key roles in helminth-induced immunomodulation. In cross-disciplinary studies in we identify glycans and glycoconjugates that trigger immunomodulatory mechanisms in in vitro and in vivo models of immunomodulation and immunometabolism. Detailed structure-function studies are supported by using libraries of purified native, (semi-)synthetic and biotechnologically engineered glycoconjugates. These studies in addition contribute to our schistosomiasis and soil-transmitted helminth vaccine development research.
Functional analysis of schistosome glycosylation in vitro and in vivo using chemical and genetic tools
The availability and exploration of genetic and chemical tools to modify and manipulate glycosylation in schistosomes is crucial to be able to conduct functional studies of schistosome glycosylation in the context of the live parasite and parasitic infections. Such studies will allow to establish for instance which specific glycan motifs are critical for successful infection, and which glycan motifs trigger immunopathological responses.