Speaker
Description
When cells are damaged or stressed, they often respond by oscillating protein densities. We show that liquid-liquid phase separations lead to condensates of repair proteins around damage sites which occur in an oscillating fashion thus preventing Oswald ripening. The period of oscillations provides an optimal time scale for the repair mechanism [1]. By applying an external periodic protein signal, the internal oscillation can lock to the external signal and thus controls the genes [2]. The locking occurs when the ratio between the two frequencies is a rational number leading to Arnold tongues. If tongues overlap, chaotic dynamics may appear [2]. When the cells are not stressed and again applying an external periodic protein signal, we obtain non-linear resonance phenomena in the genetic response [3]. The findings are supported by experimental data from our collaborative groups at Harvard Medical School and Taipei.
[1] M.S. Heltberg, A. Lucchetti, F.-S. Hsieh, D.P.M. Nguyen, S.-h.Chen and Mogens H. Jensen, "Enhanced DNA repair through droplet formation and p53 oscillations", Cell 185, 4394–4408 (2022).
[2] A. Jimenez, A. Lucchetti, M.S. Heltberg, L. Moretto, C. Sanchez, A. Jambhekar, G. Lahav and M.H. Jensen, “Entrainment and multi-stability of the p53 oscillator in human cells”, Cell Systems 15, 956-968 (2024).
[3] M.S. Heltberg, A. Jimenez, G. Lahav and M.H. Jensen, "Genetic Resonance in the p53 Signaling Network", Cell Systems, March (2026).