Microbiologist Detmer Sipkema has been awarded an ENW-M grant from the Netherlands Organisation for Scientific Research (NWO) for innovative, fundamental research. NWO announced the award today. With this funding, researchers will work over the coming years on a method to produce medicines and other bioactive compounds in sponge cells.

Sea sponges may look simple, but chemically they are remarkably sophisticated. To protect themselves against pathogens and other threats, they produce a wide range of bioactive substances, including antibiotics and molecules that inhibit cell division. These properties make sponges highly interesting for medical research. Detmer Sipkema, Associate Professor of Microbiology, has now received an NWO grant of over €400,000. With this funding, he will appoint postdoctoral researcher Kylie Hesp, who will focus on producing medically relevant sponge compounds in the laboratory. Not in whole sponges, but in cultured sponge cells.

Proof of concept
Until recently, this was considered unfeasible. Sea sponges, or isolated sponge cells, proved difficult to keep alive outside their natural environment. That barrier has recently been overcome by Wageningen researchers — including Sipkema and Hesp — working together with colleagues in Florida. “For the first time, we can keep sponge cells alive for extended periods in the lab,” says Sipkema. “That allows us to do something that was simply not possible before: cultivating sponges for their valuable compounds.”

In the first phase of the project, the researchers will focus on barrettide, a small protein produced by the Arctic sponge Geodia barretti. In nature, this molecule prevents bacteria from forming a biofilm on the sponge’s surface. The choice for barrettide is deliberate and practical. “We know for certain that this sponge produces this compound itself, and we already have part of the genetic blueprint for its production,” Sipkema explains. The molecule therefore mainly serves as a model system: if the approach works, the researchers will later move on to other compounds with greater medical relevance.

External triggers and master regulators
One challenge is that sponges do not produce bioactive compounds continuously. In their natural environment, production is typically triggered by stress, such as physical damage or bacterial attachment. The research team is therefore investigating which external stimuli stimulate production. “The presence of bacteria or bacterial fragments may increase output,” Sipkema says.

In parallel, the researchers will explore how to achieve the same effect genetically by selectively activating relevant genes. To do so, they will use the gene-editing technology CRISPR-Cas. “We initially focus on the master regulators,” Sipkema explains. “These are genes that activate other genes and set off a cascade of processes, like a domino effect.” The aim is to steer sponge cells towards continuous production of barrettide.

For Sipkema, the project also has a personal dimension. During his PhD research some twenty years ago, he already attempted to culture sponge cells — without success at the time. While his earlier approach did not work for the species he studied then, it does work for Geodia barretti from the deep Arctic Ocean. “It’s incredibly rewarding that it does work now, twenty years later, and that this grant finally allows me to carry out the research I had in mind back then,” says the Associate Professor.

About the ENW-M Open Competition
The ENW-M grant is part of NWO’s Open Competition and is intended for curiosity-driven, fundamental research in the exact and natural sciences. The grant provides room for high-risk ideas with the potential for major scientific impact. This year, twenty projects received funding; the Wageningen project was awarded more than €400,000.