ABSTRACT
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Max Fernkorn is first author on ‘ Med12 cooperates with multiple differentiation signals to facilitate efficient lineage transitions in embryonic stem cells’, published in JCS. Max conducted the research described in this article while a PhD student in Christian Schröter's lab at Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany and is now a postdoc in the lab of Micha Drukker and Christian Schröter at Leiden Academic Centre for Drug Research, Leiden University, The Netherlands. He studies how embryonic stem cells implement lineage decisions based on cell–cell communication.
Max Fernkorn
How would you explain the main findings of your paper in lay terms?
During embryonic development, cells robustly establish new identities and lineages. This study focuses on how changes in cell identity, often triggered by cell–cell communication, translate into a transcriptional response. Using a genome-wide screening approach, we identify key regulators involved in different stages of transcriptional regulation, including both signaling cascade regulators and components of the transcription machinery. Notably, we find that MED12, a subunit of a protein complex called Mediator, plays a crucial role in facilitating the efficient exit from pluripotency, one of the earliest cell state transitions during embryonic development.
Were there any specific challenges associated with this project? If so, how did you overcome them?
I think the strongest hit from the CRISPR Screen, Med12, is a particularly challenging gene to work with. As a component of the Mediator complex, its activity is linked to numerous cellular processes. To accurately measure the specific phenotypes resulting from Med12 knockout, we had to design highly sensitive assays, as the effects were often subtle. However, in the context of embryonic development, even phenotypes such as small delays in cell type transitions can severely impact the successful formation of an embryo. Additionally, Med12 knockout affected one of our experimental paradigms on a technical level by influencing the doxycycline-induced expression rate of the transgene Gata6. This required us to devise alternative strategies to demonstrate the effect of Med12 loss independently of this complication.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
I was most curious to see the results of the CRISPR knockout screen. The extensive experimental planning, technical optimizations and handling the vast number of cells took time and effort. I was very happy to see a workable number of genes significantly enriched, which set the stage for the entire study. Seeing a promising set of candidates for follow-up experiments was a great relief.
Why did you choose Journal of Cell Science for your paper?
Initially, we were drawn to submitting our manuscript through Review Commons, a journal-independent platform for peer review. The feedback from reviewers, combined with new experimental results, led to significant refinements in both the structure and focus of our manuscript. Ultimately, we felt that our revised study aligned well with the scope of Journal of Cell Science, one of the partner journals of Review Commons.
Not every effect is a biological phenotype. I like this image because it reminds me to always consider the potential unintended consequences of experimental perturbations. In this case, the loss of Med12 lowered the proportion of primitive endoderm cells, mainly due to its effect on the doxycycline-inducible transgene required for this in vitro differentiation paradigm.
Not every effect is a biological phenotype. I like this image because it reminds me to always consider the potential unintended consequences of experimental perturbations. In this case, the loss of Med12 lowered the proportion of primitive endoderm cells, mainly due to its effect on the doxycycline-inducible transgene required for this in vitro differentiation paradigm.
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
For this study, the guidance of my PhD advisor Christian Schröter, was invaluable. As this study involved limited collaboration, his way of thinking and ideas were very helpful to both the project and me. I am thankful for the chance to work in an environment that provided the resources and patience to establish new techniques in the lab, which broadened my horizon and also benefited other lab projects.
What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?
I started studying Biochemistry out of curiosity to learn more about related sciences, rather than with a specific career plan. My first hands-on experiences in academic research were truly fascinating – the ability to contribute to scientific knowledge, design and conduct experiments, and describe previously unknown cellular processes. I still remember very well my excitement and sense of discovery during my bachelor thesis in Prof. Till Ischebeck's lab, looking through a microscope and observing genetically modified pollen tubes behaving differently from their wild-type counterparts.
Who are your role models in science? Why?
The inspiration and motivation from my peers and supervisors have had the greatest influence on me. I have learned a lot from daily interactions, from lab meetings to coffee breaks. Additionally, listening to scientific podcasts or talks by more experienced professors provides a motivational boost. To see how science has changed over the course of someone's scientific career often leaves me with a positive impression on the progress within the respective field.
What's next for you?
After completing my PhD, I moved to Leiden in The Netherlands to work as a postdoc in the Lab of Micha Drukker, while continuing to work with Christian Schröter. Here, I am currently applying my stem cell culturing and imaging skills to find species-specific responses to cellular stress. This research could help us understand the bases for differences in cell and species longevity. My long-term aim is to keep doing research to extend scientific knowledge, though the exact position and setting in which I will do so remain to be determined.
Tell us something interesting about yourself that wouldn't be on your CV
A hidden talent of mine is juggling clubs while riding a giraffe unicycle.
Max Fernkorn's contact details: Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands.
E-mail: [email protected]
