The Wolkers lab studies T cell effector function, post-transcriptional gene regulation, and RNA binding proteins. Group leader Monika Wolkers: “We study how T cells generate and maintain responses against tumors and infections, with a specific focus on the role of post-transcriptional gene regulation.” RNA binding proteins are essential in this process. “They work just like DNA transcription factors by regulating the amount of RNA available for translation. We study the interplay between RNA and the RNA binding proteins, and how these processes are regulated.”

In her research, Wolkers maintains a healthy balance between the fundamental and clinical side. “Sanquin is a governmental organization, so we have an obligation to do research that gives back to society,” Wolkers says. “We work on understanding underlying disease mechanisms in white blood cells. But our research also contributes to the tumor immunology products used in the Netherlands Cancer Institute to treat cancer patients directly.”

Two of Wolkers’ colleagues, PhD students Anouk Jurgens and Valeria Lattanzio, work on the responses of T cells to pathogens from a molecular point of view. “We aim to understand the mechanisms that drive the production of cytokines in T cells. We specifically focus on the RNA biology,” Jurgens says. “We study sequence motifs and features in RNA, and the proteins that bind to these RNA features that define the protein production.”

To test their hypotheses, the Wolkers lab runs experiments with techniques varying from cell culture, flow cytometry and imaging, to proteomics and CRISPR-Cas9 mediated gene editing in primary T cells. “One doesn’t work without the other”, Wolkers says. “All techniques are interlinked. To form a hypothesis, we need proteomics, and to validate, we need CRISPR-Cas9 and functional assays.” The lab also brings techniques to the field of immunology that are usually allocated to other specialisms, Lattanzio adds. “Some techniques are known to work with yeasts or cancer cells. We transfer them to our field and optimize them. Sometimes, that is challenging, but it is a unique way of working. It’s gratifying to finally get a technique to work in our T cells.”

When the researchers want to use technologies unavailable to them, cooperation with other Oncode Investigators is sometimes necessary. To that end, the lab has partnered up with various colleagues in the community, Wolkers explains. “For instance, Michiel Vermeulen at the Radboud University in Nijmegen and the Netherlands Cancer Institute is an expert in the field of proteomics. Collaborating with him brings our research to the next level. We have also exchanged knowledge with the research groups of Ton Schumacher and Emile Voest. And we have just started a cooperation with Jarno Drost from the Prinses Máxima Center for pediatric oncology.”

“The cooperation that Oncode facilitates is worth its weight in gold”, Wolkers says. “Getting to know other researchers who are not in your field of work is crucial. There is a lot of value in the advice you can obtain from all the expertise that other Oncode Investigators possess. Because I am in two fields of research – immunology as well as RNA biology – I have come to appreciate that cross-pollination and seeking advice work wonders. They give me extra ways of input I wouldn’t have had otherwise.” 

Wolkers believes open communication in science is crucial as a foundation for new collaborations. “You learn from others in terms of learning techniques, looking for advice and sharing results. That generates a helicopter view allowing you to appreciate the potential in your work. You can implement that in your own research questions. This combination gives an excellent return on investment.”

“Being an Oncode lab offers lots of financial and intellectual stability to answer our research questions, as well as access to lots of knowledge,” Jurgens says. “There is always another lab that can help you understand results you don’t yet understand or try a new cool technique with which you don’t yet have experience. Also, the masterclasses that Oncode offers are a great way for PhD students to improve their knowledge of various current themes in oncology. There is a community behind us, willing and excited to help whenever necessary.”

“The Oncode community is innovative and supportive”, Lattanzio agrees. “Oncode’s signature is performing cutting-edge research and not being scared to try new things. We feel we’re constantly being helped to push our limits. Seeing that this is possible with the trust, support, and collaborations Oncode offers is great. Ultimately, it’s a lot of fun to be a part of this community.” 

Wolkers and her colleagues are conducting research that is fundamental in nature but still forms a stepping stone for other researchers to conduct clinical research. “As a group leader, I get to decide which way we go in our research,” Wolkers says. “I think it’s important to return fundamental knowledge to society. But for that to happen, I also believe it’s crucial to try new things in the science we conduct.”

Still, Wolkers’ focus on fundamental research sometimes causes problems when applying for grants. “Some funders don’t understand the value of fundamental research, keep asking for the clinical applicability of our research, and will eventually turn us down. They think we just try stuff and play around. But it goes without saying that we take opportunities when we see them. Thanks to Oncode’s non-restricted funding, we can still conduct our fundamental research, no strings attached.”

The importance of fundamental research is not lost on Wolkers’ colleagues. “We tend to forget that it has a big impact on where the clinical research is going,” Lattanzio says. “If we don’t know what is happening behind the scenes, we cannot be in the front line to help patients.”

“That’s why I like doing both,” Wolkers adds. “Even though our research probably won’t be immediately applicable in the upcoming years, the patient is always in the back of my mind.”

It is essential for researchers, both on the clinical and fundamental side of the spectrum, to realize that we are all on the same side, Lattanzio says. “The right mix of both is the key to success. For this to happen, we need to learn to communicate with each other to understand each other’s needs.” That intrapersonal approach sometimes calls for sacrifices to be made, Jurgens believes. “But working in science is all about character development.”

Credits: interview by Koen Scheerders; photography by Rob ter Bekke