Valentin Flury investigates how cell propagate their epigenetic memory

Could you describe your current area of expertise and discuss how it has evolved over the past few years?

Starting my PhD in Basel, I was very interested in comprehending the mechanistic principles governing chromatin partitioning into active and repressed domains. To do that, I used fission yeast as a model organism that contains a positive feedback loop machinery directing heterochromatin formation and could finally demonstrate that euchromatin counteracts this machinery using its own positive feedback loops. Altogether however, it was (and still is) difficult to distinguish the initial steps in such loops to establish specific chromatin states, resulting in the usual dilemma of “what comes first?” due to reduced temporal resolution.

Hence, during my postdoc, I contributed to the development of tools specifically designed to track the (re-)establishment of chromatin states over time after DNA replication, leveraging advanced genomics and proteomics techniques. This now directly allows us to estimate the individual roles of various protein complexes in chromatin state formation by combining these methods of high spatiotemporal resolution with rapid perturbation assays, such as protein depletion approaches, endogenous or exogenous stress or damage.

During your time in Denmark, you uncovered a complex mechanism by which cells preserve their epigenetic integrity and cellular identity during cell division through meticulous histone modification recycling. What research questions are you planning to explore at the Max Planck in this context?

Soon after I started my postdoc in Copenhagen, we discovered that cells use specialized machinery to propagate epigenetic information during DNA replication. This seminal finding was only possible due to an elaborate tracking system that follows each genomic locus from the moment it is replicated. This new research area promises to keep us busy as we dissect how this mechanism is regulated, identify the factors involved, and explore the crosstalk between them. We also investigated whether the mechanism offers an intrinsic opportunity to alter cell identity, such as during differentiation. Additionally, high-resolution tracking systems are lacking for most other chromatin-challenging processes, such as mitosis, transcription, and DNA damage, meaning that currently, we cannot track a locus over time after the challenge has occurred or after the complex has bound. Developing such technologies will be a primary focus of my lab.

What do you anticipate will be the most significant challenges in your upcoming projects?

An important lesson I learned during my PhD and postdoctoral studies is that biological systems act and react incredibly fast. Achieving sufficient temporal resolution is crucial for obtaining high-quality data. However, I am confident that our efforts will pay off through further development of current technologies and their integration with live-cell imaging, an area in which the MPI-IE is an absolute top address.

Which technologies do you employ to address your research questions, and what model organisms do you use in your studies?

We will primarily use advanced genomics and proteomics technologies combined with genome editing and rapid protein depletion/modulation technologies to thoroughly characterize the surroundings in which our epigenome maintenance factor of interest are embedded. Exploring how the epigenome is propagated at such temporal resolution offers many entry points. Therefore, I am excited not only to use mammalian cell culture models, particularly mouse embryonic stem cells, but also to bring back fission yeast to the benches in my lab. This model organism will allow us to screen for epigenome maintenance proteins and can be grown in large quantities, facilitating more in-depth characterization, higher throughput, and providing evolutionary insights into conserved mechanisms compared to mammalian systems.

What inspired you to pursue a career in science?

I have always been intrigued by the complexity of systems and how they can be broken down into many interconnected building blocks. Moreover, different biological systems offer the most amazing, diverse, and innovative solutions to overcome their challenges making the process of dissecting them so enjoyable.

What is the most valuable piece of advice you have received related to your scientific career, and how has it influenced your approach to research?

You can only address this incredible creativity of biological systems by being innovative and diverse yourself, thus I really enjoy working in an international team with different backgrounds. Approaching a complex project with unhindered input from all peers is crucial for success. We can only progress as a team, and creative problem-solving approaches only work if there is trust among team members.

To conclude, could you share a unique or surprising aspect about yourself that people wouldn't know by looking at your CV?

Until my last year in high school, I actually wanted to study foreign languages because I find it fascinating how different languages are built and the logic behind them. In a way, a language works similarly to biological systems, with individual words as small building blocks that – when combined correctly – let you actually speak it! Yet, I am very happy to have chosen to study biological systems, as it never ceases to amaze me. Moreover, I can still speak in foreign language, either at work in an international environment such as the MPI or also at home with my trilingual family.