I am professor of biochemistry and biotechnology at Ghent University, as well as founding director and currently associate director and PI at VIB’s Center for Medical Biotechnology, in which we work to innovate biomedical molecular analytics and bio-engineering. My lab has longstanding expertise in liquid biopsy technology development based on modifications of biomacromolecules (glycosylation, methylation). In synthetic biology, my lab has 20 years of experience in pathway engineering in the eukaryotic secretory system, to customize biopharmaceutical production cells, especially through glycosylation modifications. This resulted e.g. in the GlycoSwitch glycan humanization system in Pichia pastoris; nanobody-Fc manufacturing systems in Pichia for oral and respiratory delivery, as well as yeasts glyco-engineered for efficient lysosomal enzyme replacement therapies. Further synbio projects are in glyco-engineering of mammalian cells. Research in my lab has been funded by Marie Curie Excellence (2005-2009), ERC Consolidator (2014-2019) and ERC Advanced Grants (2023-2028), and presently also by Gates Foundation.

Keynote Details

Tuesday 30 June

Symposium 15: Eukaryotic microbial cell factories

Development of the OPENPichia open-access industrial Pichia pastoris protein production system and use for manufacturing of anti-infectious VHH-Fc antibodies.

The yeast Komagataella phaffii (historically referred to in biotechnology as Pichia pastoris) is widely used for producing recombinant proteins, with many used in the clinic, in industrial processes and in food. However, the origin and derivation of the basic strain NRRL Y-11430, from which all commercial hosts are derived, is formally undocumented, and access to its patent-associated deposit has had costs, complexities and enduring restrictions much beyond the lifetime of the original patents. We have investigated the background of the industrial strain, and engineered an equivalent open-access chassis strain, which we refer to as OPENPichia.
Illustrating the industrial readiness of the system, we have used OPENPichia as the chassis for all of our work in engineering a stabilized non-N-glycosylated VHH-Fc antibody format, developing optimized manufacturing strains and simple repeat-fed-batch processes. In this collaboration with the Gates Foundation, we achieved space time yield of production at par with highly optimized CHO fed batch production of this key antibody type. We demonstrate this technology by manufacturing of sarbecovirus-neutralizing antibodies. In related work, we have engineered VHH-Fcα molecules and oligomeric VHH molecules for production in Pichia, to be formulated into dried feed/food to combat gastro-intestinal pathogens. We have demonstrated efficacy in a swine model of Enterotoxigenic E. coli (ETEC), of use in veterinary medicine, and subsequently developed by our startup Animab with a goal for market entry in 2026. We have recenty built on this technology for development of a food-administered antibody that can prevent lethal Clostridiodes difficile disease in the mouse model.