Puck Knipscheer is a group leader at the Hubrecht Institute and an Oncode Investigator. She has been part of Oncode Institute since its start. Knipscheer’s team studies molecular mechanisms and regulation of DNA repair. “I like to get to the bottom of things,” she says.

“I wanted to become a farmer for a while because my father’s family has agricultural roots and I loved staying at the farms. At high school, I liked the science classes, chemistry in particular. So, I decided to study molecular sciences at Wageningen University, which combines biology, chemistry and physics. I had a great time in Wageningen. I did not specifically aspire to be a scientist at that time. To be honest, I thought scientists were rather peculiar people.”

“From the moment I started internships, at Wageningen University and later at the Netherlands Cancer Institute, my interest in science was sparked. I enjoyed unravelling the molecular details of biological processes. I am a ‘precisionist’ and a curious person. I am also very interested in the lives of my family and friends, and in what is going on in the world. I guess perfectionism and curiousness are useful traits for a scientist. I decided to go for a PhD position in Titia Sixma’s group at the Netherlands Cancer Institute. We used X-ray crystallography and biochemistry to investigate posttranslational modification by SUMO proteins. This fascinated me.”

“Next, I wanted to work in a more physiological system. I went for a postdoc position in the laboratory of Johannes Walter at Harvard Medical School in Boston. We developed a Xenopus egg extract-based model system to study DNA repair under physiological conditions in vitro. After four years in Boston, I returned to the Netherlands to establish my own research group at the Hubrecht Institute. I guess this was the moment that I decided to try to make a living as a scientist.”

“I strategically chose institutes that would provide a stimulating environment. For instance, Johannes Walter’s group in Boston was a relatively small and novel group at that time. There was a lot of coherence in the team. Johannes was not the type of ‘always on the road’ established scientist. He was actively involved as a supervisor and has inspired me very much. And Boston has a very nice atmosphere; it is almost as if science is in its air.”

“When I returned to the Netherlands in 2011, the Hubrecht Institute actually was not an obvious choice. It mostly focused on cell biology, stem cells and animal models at that time; there was little biochemistry and protein work going on. However, it was a dynamic and young institute and I figured it would offer a stimulating environment. I have been there for nine years now and I never regretted my choice. The Hubrecht has a very collaborative spirit: we help each other out. I also extensively collaborate with other institutes. Being an Oncode Investigator has helped me to expand my network of collaborators. Of course, researchers manage to find collaborators themselves based on mutual interests. However, this process is sped up by regularly meeting each other and discussing science, which is facilitated by Oncode.”

“My group studies the molecular mechanisms that keep our DNA healthy. We study the repair of two types of DNA damage: interstrand crosslinks and stable secondary DNA structures called ‘G-quadruplexes’. We use the Xenopus egg extract experimental system to obtain a detailed understanding of these processes, and we supplement this with mass spectrometry and biochemical, biophysical and cell biological techniques.”

“Our research has obvious links to clinical practice even though it is strongly fundamental. The molecular processes that guard the integrity of our DNA protect us from cancer. In a recent Nature publication, we revealed the molecular pathways that are involved in repairing alcohol-derived DNA crosslinks. Cancer may arise if these pathways are impaired. This was a collaboration with the MRC Laboratory of Molecular Biology in Cambridge. In addition, chemotherapy causes DNA damage, which is repaired with the mechanisms that we study. Insight into these molecular mechanisms may facilitate innovation in treatments.”

“My main drive is my desire to understand the detailed biochemical aspects of DNA repair, to get to the bottom of things. Curiosity is a great motivator. I want to discover relevant things that nobody knew before and have fun on the road to these discoveries. And I want to educate young scientists so that they will also experience passion and pleasure from science. It makes my day when one of my researchers enters my office with a successful experiment. This doesn’t need to be a big breakthrough; it may just be a small technical advancement or so.”

“As a starting scientist, it was difficult to compete against established researchers. It was a challenge to obtain funding and to attract talented young researchers to my group. This has become easier now, but grant writing is a continuous effort. Participating in Oncode allows me to start projects that would be difficult to finance elsewhere.

“Yes and no. He is a group leader at the Netherlands Cancer Institute. It is nice that we can discuss science and our experiences in managing a research group over dinner. We even collaborated recently. But our six-year-old daughter provides a welcome distraction. Sometimes it is challenging to balance two scientific careers in one family. Most of the time, it is rewarding to have such an exciting job that perhaps one day might help clinicians to outsmart cancer.”

Credits: interview by Linda van den Berg; photography by Marloes Verweij, Laloes Fotografie