Zoher GUEROUI " Engineering phase separations in cells to manipulate biomolecular condensates"

Abstract : It is increasingly recognized that biomolecular condensates contribute to the organization of cellular biochemistry by concentrating and compartmentalizing proteins and nucleic acids. They participate in many vital processes, such as RNA regulation, thereby shaping overall gene expression. Importantly, their dysfunction has been linked to viral infections, cancer, and neurodegenerative diseases. Despite their complex biochemical and biophysical properties, recent discoveries suggest that phase transitions—ubiquitous in non-living matter—can provide a useful framework for understanding the formation of viscoelastic biomolecular condensates. In this context, we are developing novel tools to enable the controlled formation of phase-separated condensates with defined compositions and properties in cells (1–5). Using these engineered condensates, we aim to address fundamental questions: How does RNA influence condensate biophysical properties? How does active transport by molecular motors shape condensate formation? Can endogenous organelles be harnessed using such engineered condensates? 1) Cochard A., Garcia-Jove Navarro M., Kashida S., Kress M., Weil D., and Gueroui Z. Biophysical J. 2022. https://doi.org/10.1016/j.bpj.2022.03.032 2) Garcia-Jove Navarro M, Kashida K, Chouaib R, Souquere S, Pierron G, Weil D, and Gueroui Z. Nat Comm. 2019. https://www.nature.com/articles/s41467-019-11241-6. 3) Cochard A, Safieddine A, Combe P, Benassy M-N, Weil D, Gueroui Z. Embo.J. 2023 .https://doi.org/10.15252/embj.2023114106 4) Piroska L, Fenyi A, Thomas S, Plamont MA, Redeker V, Melki R, Gueroui Z. Sci Adv. 2023. https://www.science.org/doi/full/10.1126/sciadv.adg5663 5) Amari C, Simon D, Bellon T, Plamont MA, Thiam AR, and Gueroui Z. Controlling lipid droplet dynamics via tether condensates. Nat. Chem. Biol. (2025). https://www.nature.com/articles/s41589-025-01915-2