‘It’s really a miracle that cancer doesn’t occur more’
On 19 June, a press release announced to the world that you had won the ‘Dutch Nobel Prize’. What were you doing that day?
“In mid-May I was called by Stan Gielen, President of NWO, who told me I would be getting the Spinoza Prize. I was glad to be able to finally share the news with my research group on 19 June. It just so happened that I had scheduled a meeting with them that day to discuss our future plans. Of course I brought cake for everyone!”
Do you have an idea what you are going to spend the money on?
“About five years ago I chose a new direction: DNA replication in eukaryotes [ed.: eukaryotes are organisms that have cells containing a nucleus with DNA], i.e. copying DNA using a protein machine. This can go right, or it can go wrong. I examine the replication process at the molecular level and I am keen to explore this in more depth.”
How does copying DNA with a protein machine work?
Dekker draws two horizontal lines one above the other. “This is a DNA strand of two nanometres thick.” At the end of the strand, it splits into a line that slants upwards and one that slants downwards. Do you recognise the replication fork yet? The DNA is copied by the replisome, a protein complex that, in cells like ours, consists of 25 proteins. “All those proteins have to work together in an aqueous environment that contains countless other proteins. Collisions with the water molecules cause the whole to vibrate pretty much continuously. So it’s a miracle that DNA replication so often goes right.”
Our bodies copy DNA millions of times a day to create new cells. How often does that go wrong?
“If we include damage repair, it goes wrong in one out of one to the power of ten nucleotides [ed.: nucleotides are the letters that make up our DNA]. In other words: for every ten genomes [ed.: a genome is your complete DNA] that are copied, one will contain an error. That is not often. But when it does really go wrong, it can lead to a genetic disease, cancer or ageing.”
But if it doesn’t often go wrong, why do so many people get cancer?
“All of our cells together copy about a light year [ed.: 9.5 trillion kilometres] of DNA in our lives. That’s incredibly long, all the more when you consider how tiny DNA is. So you may think that one in three people getting cancer is a lot, but it’s really a miracle that it doesn’t occur more. I want to understand why.”
Can certain properties of DNA in tumours be traced to errors in the replication process?
“I am trying to improve our understanding of the molecular aspect of DNA replication so that we can find out what can stop the replication fork and what the consequences are for the DNA. I am currently building a consortium which will examine these molecular and cellular processes in relation to replication. We are also collaborating with research groups that are studying certain tumour cells that are known to be able to cope more flexibly with faulty DNA replication. If we can gain a better understanding of how this works, we may be able to exploit certain sensitivities of tumour cells by administering specific molecules and ultimately prescribing better treatments. It’s motivating to be able to contribute to this work.”
As a physicist, what is it that makes you so interested in such biological processes?
“It interests me that while the whole replication process is an exceptionally well-functioning machine, at the same time it evidently does not always function well. As a scientist, I try to understand the whole machine.”
You studied mathematics and physics at Yale, graduated in physics at Leiden University and obtained your PhD in physics at Harvard. What is the source of your fascination with physics?
“My father has a background in physics, so it wasn’t new for me. When I was in secondary school, I learned about Watson and Crick’s discovery of the DNA structure in Biology class, but I didn’t find it that interesting at the time. I was more interested in mathematics and the other more exact sciences. I had an aha-experience when I learned about the link between the periodic table of elements and quantum mechanics. I was fascinated when this led me to understand how each element is arranged according to a fixed pattern. But I’m glad I did not just study sciences at Yale; I also studied French, music and many other subjects.”
Why did you return to the Netherlands?
“After I received my PhD I did a postdoc in Paris, so I was already more in the neighbourhood. Cees Dekker [ed.: Professor of Biophysics] told me in 2001 that he was developing a biophysics research group in Delft. I visited them and they offered me a position. I had the feeling that the people there knew what they were doing and that I could do the research I wanted to do there. So I accepted their offer, also because I felt that I would have more freedom to organise my life the way I wanted to here; at Harvard, I felt like I was part of a rat race.”
What do you do when you are not working?
“I like to spend time outdoors walking, jogging or cycling. I regularly bike the thirty kilometres from my home in Leiden to my work in Delft. I bike at a relaxed speed, because life is already fast enough as it is. I don’t want to have any commitments outside my work, so I really exercise for the fun of it. I’ve also been singing in a local choir for the past year or two.”
You have been with TU Delft eighteen years now. What gets you out of bed in the morning?
“Research. I work with fantastic people in my research group and like to bring people together and share my enthusiasm for the research.”
When you came to TU Delft, the university was not yet very involved in fundamental biology. Why did you seek to make a connection with that field?
“When I started in Delft, Biophysics was housed in the Applied Physics building. That was fine at first, but as a biophysicist you really need to have a link with biology. On 1 January 2010, we had the opportunity to start a new Bionanoscience department. This was an important step for the development of TU Delft. You now see more biological research being conducted throughout the university.”
You were the first female board member of the Foundation for Fundamental Research on Matter (2012-2017). Do you see yourself as a role model?
“It doesn’t feel like it, but I probably am. Fifteen percent of physics students are now women, and there are even more in nanobiology. I used to give talks on information days. I offered to do so again recently, but something came up, which is a pity, because that’s the time to recruit women.”
As a female scientist you are cited less often than the men. Does that bother you?
“I do not experience any barriers whatsoever as a female scientist. Sometimes an article or grant is rejected, but there are always plenty of other sources of recognition available. I cannot claim that being a woman has been a handicap in my career. For example, there were only two or three women at Yale who studied physics, so in terms of name recognition it worked in my favour.”
What are your plans for the future?
“My research group is working to increase our quantitative understanding of existing biological processes and systems and deploys biophysics and biochemistry to this end. My goal for the next 10 to 15 years is to integrate this research with cell biology, bioinformatics and other related disciplines. This will enable us to maximise our impact, including, hopefully, on medical research.”