Q&A with Johan Gibcus
Johan is an Assistant Professor in the DSB. He studies the spatial organization of the genome and how this changes during development and disease.
Tell us a little bit about yourself. Where are you from?
I grew up in the north of The Netherlands in a small town on the outskirts of Groningen. It was – and still is – a typical small town where everyone knows everyone, and where today’s parents had been in elementary school together. My parents and my younger brother still live there. In fact, my grandparents and most of their entire family lived within a 20-mile radius of each other.
Describe your scientific background (What turned you on to biology/science in the first place)
I was never a brilliant student, but I have always been curious and stubborn. I remember two moments that defined my scientific career. First, it was the realization in my teens that I actually knew things that my parents did not know. The second realization came during my first year of biology undergraduate at the University of Groningen. I passed a genetics exam, which half of the class failed. From then on, I reminded myself to never be afraid to ask questions: if I don’t know the answer, chances are that half of the audience doesn’t know.
After finishing my undergraduate in biology, I stayed in Groningen to study gene amplifications in head and neck cancer using DNA microarrays. At this time, the sequencing of the human genome was still incomplete, but the bacterial artificial chromosomes (BACs) that were used for sequencing the genome were available for the scientific community. I hand-selected clones with DNA from human chromosome 11 and printed them on a glass slide to perform comparative genomic hybridization. This allowed us to identify the location and extent of copy number changes in cancer cells. This work led to the identification of new oncogenes that were associated with decreased disease-free survival in patients with head and neck carcinomas.
It was 2005 when I heard that Job Dekker had found a way to study DNA folding. Thinking that DNA microarrays would be a great tool for this, I contacted Job and he invited me to do a postdoc in his lab. I was thrilled! But I declined the offer in favor of a relationship in the Netherlands. I never forgot about the work in the Dekker lab, and I kept following their progress. After a postdoc in Groningen, where I studied the role of microRNAs in Hodgkin lymphoma, I contacted Job again. I wrote and obtained 2 fellowships to study the role of non-coding RNA in DNA folding and I finally left Groningen to join the Dekker lab in 2010.
What types of scientific projects interest you? What drew you to your current research?
I have always been fascinated by evolution and how information is stored and used in biology. To me, information is the driving force in biology that sets it apart from chemistry. Disorder (entropy) and complete equilibrium – as observed in chemistry – contains no information and is actively avoided at every level of biology. Since I heard of the sequencing of the human genome, I got interested in how cells store information in DNA. The realization that information can be more or less accessible by how DNA is folded inside a cell made it an ideal subject for me to study.
What technologies do you apply to your projects?
The most important technique in any of my recent work is Hi-C. It was the first technique to produce a comprehensive, genome-wide view of how DNA is folded inside a nucleus. When I got to the Dekker lab, the technique had just been established, and I was fortunate to be able to use it and help improve it. Although the technique has fully matured, we are still making improvements on efficiency, accuracy and usability. Mostly, we are still learning how to analyze and interpret the data obtained from Hi-C.
In 3-4 sentences can you tell us what you think are the key main findings from your recently published paper.
Our latest work in Science describes what happens when the machines that form mitotic chromosomes encounter one another. We combined microscopy, Hi-C and polymer modeling to visualize changes in chromosome folding after a timely depletion of one or more essential components of DNA folding machines.
What was the most exciting moment for you, or was there a particular result that surprised you in relation to your current paper?
One thing I have always loved about Hi-C is that the results are very visual. Some of the results from this paper were so visually striking that I was literally speechless when I first saw them. I will never forget that moment and sharing the excitement with the team.
What was the most difficult experiment to carry out successfully for this manuscript?
The most difficult experiment was to synchronize cells twice within one cell cycle while degrading or replenishing critical DNA folding machines. This allowed us to discriminate between two machines that are seemingly identical but get loaded in either S-phase or G2.
Collaboration was important for the project. Can you tell us about the collaboration and why it was especially important for these projects?
This project started as a collaboration in 2014 between 3 teams with unique expertise in DNA folding, microscopy and polymer physics. The composition of the team, combined with mutual trust, transparency and vision have allowed this project to produce 2 comprehensive Science papers. This collaboration is very special because (1) the project far exceeded the time of a PhD thesis or postdoc project and (2) not many labs can afford “only 2 papers” coming out from a substantial 10-year investment. I was very fortunate to be part of this!
What excites you most about the future of science? What are the big future questions in your field?
The most exciting thing about science is that it is progressive: every experiment brings some knowledge that was hitherto unknown. No matter how trivial some results may seem, they will be the building blocks of finding out how the world works.
We are now learning how folding of DNA – i.e. genotype – inside a nucleus relates to the different functions a cell can have (phenotype). Cells in different stages of the cell cycle, differentiation or aging all differ in the way they organized their DNA. These differences are undoubtedly important, but the biggest question is whether we can find ways to stably manipulate DNA folding and three-dimensional structure of a cell to dictate its phenotype.
How important have good mentors been in your research career?
Good mentors are extremely important. They are your scientific parents, and you will realize in hindsight how much of what you do as a scientist is engrained by your mentors. This can vary from small tidbits to how you think and operate as a person. At this point in my career, I am more aware of how people interact and considering how I can learn and improve my own interactions.
What is your goal(s) as a mentor?
My goal is to allow my mentees to improve. I strive to do this in a positive way through encouragement rather than punishment. The best scientists – like athletes – are internally motivated and my ambition is to spark that motivation.
Do you have any advice for other young scientists at any career stage from undergraduate through postdoc?
Most young scientists are at a time in their life where they must make choices. It is also a time in your life to consider what you REALLY want. Think about this actively; gather information and choose! When I decided to move to the US, I made a list of the 5 most important things. On the top of that list was the desire to do science in a great lab. Everything down the list was important but became secondary. I accepted that I would not see my friends and family as much as I would like, sold my house and packed everything I wanted to bring into 2 suitcases. It was an emotional and humbling experience, and I may or may not do it again. Remember that although a choice may turn out to be unfortunate in hindsight, you should never blame yourself for making a deliberate decision from the information available at the time.
What do you like to do outside of work?
Halfway through my twenties, I got injured playing soccer and switched my exercise to bike racing. I found out that I love endurance exercise! I mostly love to set a goal for something that seems beyond my limits and then train towards it. Currently, I am training for running my first marathon, and my goal is to finish it within 3 hours.