Emergence of the developmental tempo of a stem cell zoo from the organisation of its biomolecular condensates

• Applicant: Dr. Alberto Hernandez Armendariz
• Subject Area: Cell Biology ; Developmental Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 560872005

Life is highly dynamic. Every life form experiences time differently, for instance, bigger animals tend to have slower physiological times, such as longer gestation periods, longer life spans, and longer cardiac cycles. However, the pace of mammalian embryogenesis does not correlate with the organism’s mass. Instead, it correlates with their cell-autonomous biochemical reaction speeds, such as mRNA processing and protein degradation. In other words, the faster a mammal processes its RNAs and degrades its proteins, the faster its embryogenesis. Nevertheless, it remains unclear the spatiotemporal mechanism by which different biochemical reaction speeds emerge. A plausible mechanism might rely on how different species organize their intracellular reactions. Recently, it has been shown that biomolecular condensates could dynamically promote or inhibit enzymatic reactions. Therefore, the proposed project aims to address whether the biochemical reaction speeds and developmental timing can be regulated by the intracellular organization of biomolecular condensates. We will do this by characterizing the stem cell zoo, generated by the Ebisuya Group (Physics of Life TU Dresden), which comprises pluripotent stem cells of different mammalian clades that can be differentiated into any germ layer, state-of-the-art multiplexed imaging, machine learning, omics and theoretical approaches - in collaboration with Hyman, Sbalzarini and Toth-Petroczy Groups at MPI-CBG and CSBD. By quantitatively comparing the biomolecular condensate organization of the stem cell zoo and its thermodynamic landscapes, we expect to uncover the underlying principles dictating the emergence of biochemical reaction speeds from the intracellular organization that concomitantly contribute to the emergence of developmental tempo. The outcome of this work will generate invaluable information for the developmental and evolutionary biology fields, in addition to the rising field of biological phase transitions and the further improvement of machine learning algorithms and high-throughput approaches that could be adapted to other biological systems.

• DFG Programme: WBP Position