Valentin Flury investigates how cell propagate their epigenetic memory

New Max Planck research group wants to understand chromatin dynamics across the cell cycle

June 25, 2024

Valentin Flury has joined the Max Planck Institute of Immunobiology and Epigenetics in Freiburg as a new research group leader. His newly established lab aims to understand chromatin dynamics and plasticity throughout the cell cycle and to dissect the mechanisms of histone inheritance and epigenetic memory during DNA replication.

Humans and other multicellular organisms consist of over 250 different cell types, despite all having the same genetic information. This impressive diversity is partly regulated by their epigenome, specifically through chromatin states that control and maintain cell type-specific gene expression programs. However, chromatin, the functional packaging of DNA, undergoes significant changes during each cell division, particularly during DNA replication, when chromatin is disrupted to facilitate DNA synthesis.

The new independent research group by Valentin Flury aims to understand how chromatin states are propagated, restored, and regulated and to what extent their deregulation affects cell identity in both healthy and diseased cells.

“On top of the genetic information epigenetic information instructs the cells to remember their function and identity,” says Group Leader Valentin Flury. “Yet, whenever a cell divides, it undergoes numerous challenges, such as DNA replication and mitosis that need be overcome to faithfully propagate that information. In the last years, we have realized that specialized machineries are in place to govern this propagation, but the mechanistic details and their individual impact on cell function remain largely unclear as well as whether these machineries are regulated during development. Thus, I am very excited to start dissecting the molecular mechanism governing epigenome maintenance and I couldn’t imagine a better place to start doing that than the MPI-IE. Here, we are embedded in a stimulating environment with outstanding colleagues working in diverse developmental systems and state-of-the-art facilities that will allow us to implement new technologies and address ambitious projects.”

Welcome to the Institute, Valentin!

Interview with Valentin Flury: Question for the new group leader at the MPI-IE

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.


Valentin Flury studied biochemistry and molecular biology at the University of Bern (Switzerland). He completed his Ph.D. at the Friedrich Miescher Institute for Biomedical Research in Basel (Switzerland) studying how active chromatin is protected from being silenced. Following his Ph.D., Valentin Flury conducted postdoctoral research at the Novo Nordisk Foundation Center for Protein Research (CPR), University of Copenhagen (Denmark) under the mentorship of Prof. Anja Groth. His research centered on deciphering the mechanisms of how epigenetic information is propagated and maintained across cell divisions with a focus on histone recycling during DNA replication and subsequent restoration of the chromatin landscape. In 2024, Valentin Flury was appointed as an Independent Research Group Leader at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg (Germany).

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