International team investigates the key to longer life in yeast

Yeasts have been reliable workhorses in biotechnology for centuries. Not only do these micro-organisms make our bread rise and ferment beer and wine, but with small modifications to their DNA they can also produce valuable compounds such as insulin, antibodies and food proteins. Unfortunately, yeast cells often die during production, for example as a result of stress. This is problematic: when cells burst, their contents are released, and substances from inside the cell can damage or contaminate the product.

“What we really want is to get as much out of each yeast cell as possible,” says Mark Bisschops, Assistant Professor of Bioprocess Engineering and project coordinator. “That means persuading the yeast to live longer while continuing to produce.”

To achieve this, scientists first need to understand how and when yeast cells die. The project therefore starts at a fundamental level: identifying the molecular pathways and genes involved. “Once we understand these pathways, we can try to block them, so the cell stays alive,” Bisschops explains. This could involve selectively switching genes on or off that play a role in triggering or preventing cell death. However, the picture is complex. Like human cells, yeasts have multiple forms of regulated cell death, each following its own molecular route – and much about these mechanisms is still unknown.

So far, most knowledge about these pathways comes from fundamental research in a single yeast species: the classic baker’s yeast Saccharomyces cerevisiae. Industry, however, uses many other yeast species, which may have their own distinct molecular signals. “Yeasts that originate from very different environments are adapted to different conditions and therefore respond differently to factors such as temperature and salt concentration,” says Bisschops.

In addition to baker’s yeast, the new project will focus on three widely used industrial yeast species: Komagataella phaffii (also known as Pichiapastoris), Yarrowia lipolytica and Debaryomyces hansenii. Each has its own strengths. K. phaffii excels at producing and secreting proteins, Y. lipolytica can store large amounts of fat, and D. hansenii originates from saline environments and thrives at high salt concentrations. Baker’s yeast, meanwhile, performs surprisingly well in the absence of oxygen. “It is precisely these differences that make them so interesting,” says Bisschops. “We want to know which cell-death mechanisms are shared and which are species-specific.”

From 2026, no fewer than thirteen PhD candidates will work on this challenge. Three will be based in Wageningen: two within the Bioprocess Engineering chair group and one in Systems & Synthetic Biology. The others will be spread across six partner universities in, among other countries, Denmark, Austria and Portugal.

For each yeast species, two PhD candidates will study how cell death is triggered: one focusing on genetic pathways, the other on process conditions in the bioreactor. Other researchers will develop models to predict when cells die or design measurement methods to monitor this during ongoing processes. To actively exchange knowledge and learn from one another, each PhD candidate will spend several months on secondment with another research group and with an industrial partner.

The thirteen PhD candidates will be based at: Wageningen University & Research (Wageningen, the Netherlands), Universidade de Minho (Braga, Portugal), Technical University of Denmark (Copenhagen, Denmark), ACIB (Vienna, Austria), Imperial College London (United Kingdom), University of Milano-Bicocca (Milan, Italy) and Chalmers University of Technology (Gothenburg, Sweden).

The project is funded by the Marie Skłodowska-Curie Actions (MSCA) Doctoral Network, part of the Horizon Europe programme that supports the training of PhD candidates. The emphasis is on international partnerships between universities, research centres and companies. Projects receive funding of around €4 million. Bisschops received confirmation of the grant in 2025. “I really had to pinch myself,” he admits. “I had been thinking about this idea for a long time, and being able to carry it out on this scale is fantastic.”

Recruitment of PhD candidates has started this January. The research itself will fully get under way over the course of 2026, once all researchers have started. For Bisschops, it feels like the beginning of something significant. “This could mark the start of more efficient production processes that can better compete with traditional, fossil fuel-based methods. At the same time, we are providing multidisciplinary training for a new generation of scientists who can go on to take leading roles in biotechnology in Europe.”

Read more about the Marie Skłodowska-Curie Actions MSCA Doctoral Network.