Interview with managing director Jeroen den Hertog

What inspired you to become a scientist and at what stage did you decide to choose a career in academia?

Initially, when I was young, I wanted to become a pharmacist in order to earn a lot of money. Then I got the advice from my father to study one of the more fundamental sciences, like chemistry or biology. I listened to him and specialized in Biochemistry. I decided to pursue an extra major in Biotechnology and I found it all very interesting. At that moment, I could have gotten a job in the industry but I decided to pursue a PhD degree. I thought: I can always join the industry after that, at a more senior level, which also means more money. By the time I finished my PhD at the Hubrecht institute, I was really hooked on research and I forgot about the industry and the money, so I decided to do a postdoc. It was a great opportunity to go abroad; I went to San Diego. That was very nice and interesting, both in terms of my career in science and life in general. I had received a fellowship that allowed me to go to the United States for 2 years but one of the conditions of this particular grant was that I had to return after that. That’s what I did and before I knew it, I had basically gotten stuck in academia.

That’s a very interesting way of saying it. I think it was a very active way of getting stuck.

Yeah, it was not the default situation. In principle, science and academia are not the easiest way to go. You have to be really determined and it’s not easy to get a permanent position. It has never been easy, that is something that people tend to forget. It is tough, it has always been tough.

How did you get your current position?

During my Postdoc at the Salk institute, I focused on the regulation of phosphatases and when I returned to Netherlands there coincidentally was a new group leader position that had opened at the Hubrecht Institute. Based on my PhD work I was offered this post. It was a very attractive offer, so I took it.

Did you have a plan B for your career?

My career actually was my plan B. Plan A was to go to industry and make a lot of money. But of course, if academia hadn’t worked out for me, then I would have probably worked in the industry now. And industry is not better or worse than academia, it’s just different. What I hear from people in the industry is that it’s more of a group effort. I mean, of course we also collaborate at the Hubrecht, but if you are doing your PhD project… It’s your project, it’s all up to you, while in industry, there is often a group of people that all work towards the same goal. And when you achieve that goal, there is the next problem and therefore the next goal. That can be very rewarding as well.

What experiences shaped you as a scientist?

During my postdoc period, I had a very exceptional mentor. We did not even have that many interactions but he was very inspiring and his mentorship shaped me as a scientist. And as a graduate student, I was also very lucky to be in a lab with a very conducive environment. We had a group of grad students who were really eager and competitive but in a friendly way. We pushed each other to do better than we thought we could. That combination has really shaped me as a scientist.

Who are your role models?

I think role models are very important. My Postdoc mentor, Tony Hunter, was a real role model for me. I don’t think he even realizes it. He would leave people alone and allow them to grow independently. He was very hands-off but also very knowledgeable and helpful. He would often say: “My postdocs and PhD students will have to stand on their own once they are done here, so I am already teaching them to be able to do that.” But whenever you had a question, you could go to him and he was always available. And there are more people who made an impact on me, for example my elementary school teacher. Later, many scientists in the phosphatase and kinase field influenced me as well.

What do you think is the most challenging part of being a mentor and when do you know you have succeeded?

I am also very much a hands-off mentor. I always tell my students that I have already done my PhD and that it is now their turn to do theirs. It can be tough for some and everyone reacts to it differently. Some people work very well independently whereas some need more mentoring. So, you need to find the right balance with each student. When my students succeed, I know that I have succeeded as a mentor.

What is your advice to young scientists?

Get a good advisor. Someone who you trust and who can help you make decisions. I was lucky; my father was a scientist and my advisor.

So, do you think that maybe, while encouraging you to get into the fundamental sciences, your father was trying to, you know, keep you closer to his profession, so you both can talk more?

No, actually, it was the other way around. He pushed me away from fundamental science a little bit. He knew it was not the easiest way. So finally, I made my own decision. He was very happy about that, but he made sure that it was my own decision and not something he would like me to do. I think he did well there.

How do you keep the balance between personal life and career?

I have a family; we have 5 kids. Everything is possible, but you have to try to balance it and make things work. My advice would be to find a way that suits you best. There is a brief time where family and career are both most demanding but creating balance is most important. There is time for science and there is time for family. Particularly if you have small kids. They grow up quite fast and if you’re not around, you’ll miss it and, at some point, regret it.

Recently there has been a push towards promoting women in science and I think one of the easiest things would be to provide a childcare service which would allow both genders to balance personal and professional life. What do you think about that?

Yes, I agree, I think that is very important. I would definitely support that. Especially when you have young kids, there is a brief period and also the most demanding period in your career. It is also the time that you are usually full of energy, but with some extra support, you can do a lot more.

What is one thing that you love about your work and one thing that you dislike?

The diversity of my work is the best part. One minute, I am a scientist, studying different topics in the lab, and the next minute, I am talking to the Minister of Science to discuss budget. This diversity is the most interesting part. Sometimes it does get tough. The institute has really grown, and the corona crisis has really impacted the work, so the lab is revolting a little bit but it is going well. The balance is most important, so finding this balance between administration and science can be difficult sometimes and that is what I do not like much. But I do like both the tasks. Overall, I go to work happily every day.

Which scientific discovery has fascinated you the most?

That’s a difficult question, there are too many. But there are some discoveries that stand out such as PCR or CRISPR-Cas. In my own field, there are many fascinating discoveries. And the latest research is always most exciting. The last experiment from the lab that succeeded is the best discovery of that week. All these small results in the lab keep you excited and fascinated.

What is the research topic in your lab?

My research has been focused on tyrosine phosphatases for most of my career. These are a family of enzymes that counteract the activity of tyrosine kinases. Where the kinases add a phosphate group to the tyrosine residue in the protein, tyrosine phosphatases remove them. There are about 100 genes in the human genome that code for an enzyme that can dephosphorylate tyrosine. During my PhD, we started looking for them and since then I am hooked on these phosphatases. At the Hubrecht, I started looking into the biological function of these enzymes using zebrafish as a model system. One of the research directions is to generate zebrafish mutants corresponding to mutations identified in human patients: studying the molecular genetics and cell biology in vivo.

Also, about 10 years ago, a new research direction was established in the lab, unrelated to previous work. This focuses on identification of new biologically active compounds from fungi. It is a collaboration with the Westerdijk institute. We now have a library of supernatants from 10,000 strains of fungi and we are testing them for biological activity using zebrafish embryos as a model. More recently, we started looking at the antibiotic activity in the supernatants and the ultimate goal would be to discover new antibiotics.

Your lab works on very diverse topics. You were an established scientist when you decided to add a new direction to the lab, so my question is how did you timed this addition and how did your steer it?

My motivation was to really go into the analysis of the in vivo function of this particular class of genes. There was a choice to do that using a mouse model; there was a mouse colony at that time at the Hubrecht as well. Zebrafish were up and coming and a little bit of a buzz was going around due to all the mutant fish that were created by Nusslein Volhard in Tubingen. So, instead of using mice, which is very expensive, I thought it would be a good idea to use zebrafish instead. When you make a decision like that, you should realize that it takes at least 5 years before you are on top of this new topic. And you are right, I was an established scientist at that time, young, but quite established in the phosphatase field. And then you go to the zebrafish meetings and nobody knows you… that really was quite surprising. It was like a wakeup call: I have to start all over again. That is fine but it does take at least 5 years, so if you make a decision like that, then make sure that you realize this. At the same time, this was a gradual decision. I was still doing biochemistry on phosphatase regulation and had a couple of PhD students there. And when I moved into the fish field, I had a few people working on fish. At some point, we became more knowledgeable and a little established. But that was also the time when there was no way of making directed mutations in the zebrafish genome, and, I mean transgenics were just coming, so we couldn’t do much at that time, which is quite scary if you think back.

And how did the idea to work with fungi originate?

I just looked out of the window. The Westerdijk Institute has a very large library of fungi. They are characterizing the fungi and maintaining them and I thought, why not study the compounds produced by these fungi?

In the initial stage, I did not involve PhD students. It was too risky and it was industrial type of work: making the library, growing up 10,000 strains of fungi, filtering the supernatant and doing the initial analyses etc. I only had 3 or 4 technicians working on it, one of whom is still working with me on the project, Jelmer Hoeksma. It was a logistical operation. Afterwards, when the library was set up, I involved a postdoc to start to look for the function of some of the compounds. And when we knew that there were some positive hits, I involved PhD students in the project. It was still quite risky so there was also a back-up plan for the PhD students.  One of the PhD students has written a paper about it that we just submitted. He came up with a fast way to look at the mechanism of action of compounds in a particular strain of bacteria using a confocal microscope. It’s a very simple method that everybody will be able to use. Though this work is actually independent of the library itself.

Given the long career that you have in academia, what is the biggest question that you would like to answer as a scientist that you haven’t yet answered or that you are targeting?

We are still struggling to find ways to regulate tyrosine phosphatases. We don’t really know how they are regulated which means we cannot influence or manipulate their activity from the outside. From a medical point of view, there are diseases that are caused by overactivation of phosphatases. If you could inhibit them, you can find a cure for these diseases or at least reduce the symptoms. But the fungi are also very interesting, so I want to pursue that as well.

Thank you so much for taking out time from your busy schedule and giving us some more insight into your work and life.