Biography
During my PhD thesis (2008-2015), I have explored the possibilities to use tobacco plants as production platform for recombinant proteins with pharmaceutical applications, like human cytokines and antibodies. The PhD project was funded by a pharmaceutical company, and they gave me the freedom to develop my own research lines considering plant biotechnology as well as immunology. This research led to three publications in Plantbiotechnology Journal (the leading journal for plant biotechnology) and several other open access journals, like PLoS One and Frontiers in Plant Science. Furthermore, two patent applications resulted from this research.
Towards the end of my PhD thesis, I investigated the possibilities of adapting the N-glycosylation pathway of tobacco. This work was a stepping-stone to re-connect with helminth research within the Laboratory of Nematology. A collaboration was started with Prof. Hokke and Prof. Yazdanbakhsh from Leiden University Medical Center in which I turned tobacco plants into little protein factories for helminth-derived glycoproteins. The pioneering steps towards production of helminth glycoproteins on a large-scale and simultaneously mimic their native helminth N-glycan composition has led to a publication in Scientific Reports in 2017, but more importantly, is accepted with open arms as a new tool for animal parasitology research and has led to several new international collaborations and recent publications in high impact journal (e.g. Plos Neglected Tropical Diseases and FASEB Journal).
The availability of a recombinant expression platform that allows the reconstruction of native helminth glycan structures paves the way for a new direction in animal parasitology research. Glycan structures play a crucial role in parasite biology and at the host-parasite interface. Enabling the production of recombinant helminth-secreted glycoproteins with their native glycan structures offers the opportunity to develop efficient 'helminthised' vaccines. It will also allow more detailed investigation on the molecular dialogue in host-parasite interactions, which currently is hindered by the limited availability of native helminth-secreted products. My expression platform therefore allows more fundamental research on immunomodulation by helminth-secreted glycoproteins and the contribution of native glycans. In extension of this research, we are able to develop novel biopharmaceuticals, anti-helminth vaccines and diagnostic tools for helminth infections of humans and livestock.
In a proof-of-concept project (NWO-Veni project in 2019, followed up by the Plants4Nemavax project), I was able to demonstrate that a recombinant vaccine against the cattle parasite Ostertagia ostertagi relies on its native glycan composition to confer protection. Where other recombinant expression failed to produce a protective vaccine, my plant-based expression system was able to produce the recombinant vaccine, while at the same time we were able to mimick the native glycan composition. In collaboration with Peter Geldhof at Ghent University we were able to proof that glycans contribute to the protective capacity of this vaccine. This achievement is now paving the way for new collaborations and funded projects for the development of novel anti-parasite vaccines for livestock (e.g. against liver fluke) as well as human parasites (schistosomes and hookworm).
Research interests
My research focus is to understand the mechanisms by which parasitic nematodes and other helminth species modulate their host immune system. Helminths are complex multicellular organisms and employ a range of secreted glycoproteins for immunomodulation. In order to study the activity of these glycoproteins we exploit tobacco plants for the production of large quantities of these helminth glycoproteins. Several of these glycoproteins also rely on specific N-glycan structures for their function, so special emphasis is also given in engineering helminth-like N-glycans in plants. Ultimately, some of these glycoproteins can become potential drugs for the treatment of various inflammatory disorders.
Furthermore, the development of successful recombinant helminth vaccines is hampered by the inability to reconstruct natural glycan structures on helminth glycoproteins. Helminth glycans have unique and complex structures, which cannot be synthesised in current biopharmaceutical production systems, like bacteria, yeast or mammalian cells. With our plant-based expression system we are exploring the development of novel recombinant helminth vaccines with engineered glycan composition. This will offer an effective and durable way to prevent helminth infections by vaccination in contrast to currently used mass drug administration programs. Discipline
Molecular biology Parasitology Protein biology Host species
Cattle Poultry Small ruminants Wildlife Zoonoses Pathogen
Parasites Parasites›Nematodes Stage of vaccine development
Antigen discovery and immunogen design