PROJECT
SUPERVISORS

Project Supervisor

Jan Zylicz

Background

I have always been fascinated by how complex regulatory pathways mediate development. During my PhD in Cambridge (UK, 2011-2015), I became fascinated by repressive histone modifications and how they regulate mammalian development. I was surprised to find that they are vital for the decision-making process in the first week of development. I have always been interested in going beyond correlation and focusing on causality in epigenetic regulation, and I quickly realised that examining the dynamics of chromatin is vital to distinguish between cause and effect.

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That is why in 2015, I joined the team of Prof. Edith Heard at Institut Curie in Paris. There, I unravelled the finely-tuned sequence of chromatin events during X chromosome inactivation in females. During my PhD and postdoctoral work, I worked on disentangling the function of individual chromatin modifiers in regulating gene expression. In 2020, I started my independent team at reNEW (University of Copenhagen). In my team, we apply the insights from functional epigenomics and developmental biology to an emerging field of epi-metabolomics, the study of how metabolic pathways shape the chromatin status of cells.

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Research

Our focus is on uncovering the non-canonical roles of metabolism. On a fundamental level, we aim to unravel the intricate molecular mechanisms through which chromatin and metabolism regulate gene expression during early mammalian development. We explore questions such as how global changes in metabolism lead to specific outcomes, the causal relationship between chromatin alterations and gene expression changes during lineage specification, and the biological significance of the coupling between metabolism and epigenetics

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We are also intrigued by how the developing embryo interacts with its environment. We delve into how stem cells respond to their surroundings, and how these cues translate into chromatin and gene expression programs that impact embryogenesis. On a more translational level, we apply this mechanistic knowledge to address pressing issues in assisted reproductive technologies. Specifically, we aim to discern the factors contributing to early in vitro fertilization failures, seeking potential strategies for enhancing embryo quality. By delving into how chromatin senses metabolic changes, we aim to shed light on how successful development is orchestrated.

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Publications

Van Nerum, K., Wenzel, A., Muntadas, L.A., Kafkia, E., Lavro, V., Roelofsen, A., Drews, A., Arnal, S.B., Zhao, C., Sanzo, S.d., Volker-Albert, M., Petropoulos, S., Moritz, T., and Żylicz, J.° (2024). Metabolic rewiring underpins human trophoblast induction. PREPRINT (Version 1) available at Research Square. https://doi.org/10.21203/rs.3.rs-3575549/v1

Pladevall-Morera, D., and Zylicz, J.J.° (2022). Chromatin as a sensor of metabolic changes during early development. Front Cell Dev Biol. https://doi.org/10.3389/fcell.2022.1014498

Tjalsma, S.J.D. #, Hori, M. #, Sato, Y. #, Bousard, A., Ohi, A., Raposo, A.C., Roensch, J., Le Saux, A., Nogami, J., Maehara, K., Kujirai, T., Handa, T., Bages-Arnal, S., Ohkawa, Y., Kurumizaka, H., da Rocha, S.T., Zylicz, J.J.°, Kimura, H.°, and Heard, E.° (2021). H4K20me1 and H3K27me3 are concurrently loaded onto the inactive X chromosome but dispensable for inducing gene silencing. EMBO Rep. https://doi.org/10.15252/embr.202051989

Dossin, F., Pinheiro, I., Zylicz, J.J., Roensch, J., Collombet, S., Le Saux, A., Chelmicki, T., Attia, M., Kapoor, V., Zhan, Y., Dingli, F., Loew, D., Mercher, T., Dekker, J., and Heard, E.° (2020). SPEN integrates transcriptional and epigenetic control of X-inactivation. Nature. https://doi.org/10.1038/s41586-020-1974-9

Zylicz, J.J. #, Bousard, A. #, Zumer, K., Dossin, F., Mohammad, E., da Rocha, S.T., Schwalb, B., Syx, L., Dingli, F., Loew, D., Cramer, P., and Heard, E.° (2019). The implication of early chromatin changes in X chromosome inactivation. Cell. https://doi.org/10.1016/j.cell.2018.11.041