Bernhard studied Biology/Genetics at the University of Vienna. In 1999, he joined the IMP to do his Diploma thesis in the lab of Meinrad Busslinger, where he studied the regulation of Pax genes in embryonic mouse brains.
After his PhD at Cambridge University, UK, Bernhard moved to Boston for his Postdoc, working on X-chromosome reactivation in mice. At present, he is a Junior Group Leader at the Centre for Genomic Regulation in Barcelona, focusing on epigenetic reprogramming during embryogenesis and in the germline.
You spent about a year at the IMP to do your diploma work in the lab of Meinrad Busslinger. What exactly did you study?
I first did a practical (“Biochemisches Wahlbeispiel”) and then my Diploma thesis in Meinrad’s lab under the supervision of his Postdoc Peter Pfeffer, who now has his own group at Victoria University in Wellington, New Zealand. While the majority of Meinrad’s lab was focusing on the roles of Pax genes during B-cell development, Peter and I were studying how their expression would be specifically regulated at the mid-hindbrain boundary in early mouse embryos. We performed classical enhancer transgene assays, where I would clone reporter genes with different genomic enhancer fragments and then Peter would generate transgenic embryos, which I would then analyse. This would allow us to narrow down the regions which controlled the tissue-specific expression and identify transcription factors which would be the upstream regulators.
In my second project, I generated a knockout mouse for one such enhancer, which was a great learning experience for me as a diploma student, even though the knockout mouse developed completely normal brains with normal Pax gene expression. Fast-forwarding 20 years, this all makes complete sense now. New studies with current genomics methods like ChIP-Seq or chromatin conformation capture assays have shown how redundancy and failsafe mechanisms (e.g. shadow enhancers) are in place to ensure the faithful regulation of important genes. Nature just wouldn’t leave key developmental decisions in the hands of a single enhancer without having a backup in the basket.
Why did you choose the IMP and, specifically, the Busslinger Group?
There was a bit of luck involved. I have to thank mainly two people. First, Markus Hengstschläger at the AKH, in whose lab I did a practical before joining Meinrad. He recommended me (and Konrad Hochedlinger, another IMP alumnus who did his practical with Hengstschläger around the same time) to look at the IMP for a diploma position, as this was simply the best place in Vienna to do Biomedical Research. The second person of influence was Thomas Jenuwein, then a group leader at the IMP. He taught a seminar series on Epigenetics - my current field of research - at the University, which I found very exciting. So, I looked at a few labs at the IMP that I found interesting and Meinrad’s came up on top. I still vividly remember the day when I nervously entered Meinrad’s office to ask him whether he had a diploma position available, and the excitement when he said yes, I should talk to his Postdoc Peter Pfeffer. The rest is history.
Did this time, very early on in your research-life, influence or shape your scientific career in any way?
Absolutely. The time in Meinrad’s lab at the IMP was one of the most determining periods in my scientific career. Being in a top-notch institute and a lab which was truly international, where English was the working language and cutting-edge research was performed, completely changed my view on what it is to do science. My learning curve was exponential, I learned many of the methods which I would later need and, importantly, I learned how to think about and approach a scientific problem. Only then I completely realised that science does not end with text-book knowledge, but that the scientific process itself and how to address what is not known, are the really interesting parts.
From Vienna to Cambridge to Harvard and now Barcelona. Can you briefly describe the next steps and the choices you made?
My time at the IMP with Meinrad really opened many doors, due to his high reputation internationally. I wanted to expand my interest in Developmental Biology and therefore did my PhD in the Developmental Biology PhD Programme at Cambridge University, UK, in the lab of Azim Surani (Gurdon Institute). There I studied how the germ cell lineage - the precursors of eggs and sperm - would be formed in mice, a topic which was completely unsolved at the time. After a very fulfilling period in Cambridge, both professionally and privately, I moved across the ocean to Boston where I did my Postdoc with Jeannie Lee (MGH, Harvard University) on X-chromosome reactivation during stem cell reprogramming and in early mouse embryos. Being in one of the top cities for science was also a very enriching experience. The sheer number of opportunities there, both in academia as well as industry, is simply mind-boggling. Finally, I moved back to Europe to the Centre for Genomic Regulation (CRG) in Barcelona, Spain, to start my own group. Here I combine the expertise and interests from my PhD - germ cell development - and my Postdoc years - X-chromosome reactivation and pluripotency.
You career seems to have unfolded in a picture-book way. What obstacles or backlashes did you have to deal with along the way?
Of course, there is always a certain survivorship bias when asking group leaders about the obstacles they had to face. After all, we are the lucky ones who “have made it” and been given the privilege to continue following their interests in academia. Nevertheless, of course I had many challenges to overcome. The first one I had in Meinrad’s lab, where I spent an entire summer with failed cell culture experiments, only realising at the end that one key media component, prepared by another lab member, was at the wrong concentration. Besides technical challenges during my active research career - it is amazing how few experiments actually work - another challenge, for example, was the competition with other research groups who had similar findings around the same time. In hindsight, this taught me the important lesson that one should never despair when being “scooped”. First, it means that you have been on the right path and second, that you can always find another way to frame your story.
Once a group leader, I was surprised at how different the job is from being a bench researcher. I would have never anticipated the challenges associated with leading a team of people with different characters and talents and how to deal with a plethora of administrative tasks, sometimes leaving little time for science. That is one of the most fascinating parts of a scientific career: You never stop learning new skills and it truly never gets boring.
Since 2014, you are a Group Leader at the CRG in Barcelona. What is the current focus of your lab and what are your plans for the future?
My lab is interested in epigenetic reprogramming during embryogenesis and in the germline. Specifically, we want to find out how epigenetic information, which has been laid down during cellular differentiation, becomes erased again during reprogramming or germ cell development. This so-called epigenetic ground state is required for pluripotency and for preparing the genome for transmission to the next generation. As a model system, we use the mammalian X chromosome, as it is transcriptionally inactivated by epigenetic mechanisms during female cell differentiation and reactivated during reprogramming and in germ cells. Thereby, we can study epigenetic reprogramming on a chromosome-wide scale involving over 1000 genes – dramatic enough that you can even observe it under a regular fluorescence microscope.
Another focus we have is the aging process of human oocytes. We have set up a collaboration with a fertility clinic here in Barcelona which provides us with samples from young and advanced age women. Thereby, we want to find out what happens to the transcriptome during oocyte aging and how this might impact oocyte quality and fertility.
As the CRG has a maximum tenure of 9 years for junior group leaders, I will soon have to look for positions at other Research Institutes and Universities to continue and expand our research lines. Where this will take me? Time will tell.
Do you have any fond memories of your time at the IMP that you want to share?
Many. Two from the IMP recess come to my mind. One of the proudest moments in my career was when Meinrad introduced me to a member of the Scientific Advisory Board and told him that I just succeeded in creating a knockout-mouse as a diploma student (after that summer of failed experiments mentioned above) – a non-trivial feat in pre-CRISPR times. This taught me how important it is to give credit to the people working with/for you, as these are the moments they will always remember.
A funny anecdote from that recess was the lunch, where I sat with Michael Glotzer and Peter Pfeffer and had my very first Sushi. Not knowing what that green piece was on my plate next to the Sushi, I put the Wasabi into my mouth as a whole. Not wanting to embarrass myself in front of everyone around me, I slowly let it dissolve in my mouth, almost suffocating from its spiciness, but swallowed it slowly not saying anything. Another important lesson I learned at the IMP: be sure to know what you put in your mouth.
How do you like living in Catalonia/Barcelona and working at the CRG? How does it compare to Austria/Vienna?
As an Institute, the CRG has many similarities with the IMP. An excellent international scientific environment, with great support and a pure focus on research. Outside the institute, Barcelona has a vibrant science community, certainly comparable to Vienna. What is better in Austria is the amount of funding one can obtain through national grants.
As a place to live, I must say that I absolutely love Barcelona, maybe even more so than I did Vienna. The combination of a great cultural city with Mediterranean climate and amazing surroundings are very hard to beat. Especially as an outdoor lover, exploring the surroundings of Barcelona by foot and bicycle every weekend make it really feel like living in paradise for me.
Looking back, would you make the same choices again?
Absolutely. I would not change anything. The IMP was a great formative kickstart for my science career. Moving abroad after that was also a great choice, which I recommend anyone to do. I think experiencing new cultural environments, seeing how science is done elsewhere and making international friends are extremely enriching experiences which I would not have wanted to miss. Let’s see, if, and when I will eventually settle down somewhere for good. I certainly miss Austria sometimes, but I regularly visit my family back in Carinthia and see old friends in Vienna. Once you have been living abroad, you often discover the true beauty of your home country.
Interview by Heidi Hurtl, 2021
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