CoSy seminar: "The role and tunability of p53 oscillatory dynamics in DNA repair: from regulation of biomolecular condensates to entrainment to external periodic signals"

Everyone is welcome and the first 40 people to register will be treated to a free lunch sandwich. If you do not want lunch, you are still welcome to join.

Register for a lunch sandwich (deadline: Sunday 4 Febrary)

Abstract:  The p53 transcription factor, also known as "guardian of the genome," is crucial for cancer prevention and maintaining genomic stability. When multiple DNA breaks occurs, p53 levels oscillate with a robust period of 5.5 hours, whose functional role is still highly debated. In this work, we construct a theoretical model to show how p53 temporal dynamics optimize repair rates by controlling condensate formation and spatial distribution of repair proteins around damage sites, ensuring efficient resource allocation in cells [1].

Subsequently, we explore the possibility to entrain (or frequency-lock) p53 dynamics to an external pulsing signal. We reveal that the p53 network can portray a wild array of complex dynamics, including higher-order entrainment, multi-stability, and chaotic dynamics [2].

Overall, these insights shed light on how p53 oscillations, external signals, and cellular processes interact, advancing our understanding of cellular regulation and decision-making.

In both works, our theoretical predictions are in great agreement with experimental data from our collaborative groups at Harvard Medical School, and Academia Sinica, Taiwan.

[1] Heltberg, M. S., Lucchetti, A., Hsieh, F. S., Nguyen, D. P. M., Chen, S. H., & Jensen, M. H. (2022). Enhanced DNA repair through droplet formation and p53 oscillations. Cell, 185(23), 4394-4408.

[2] Jimenez, A., Lucchetti, A., Heltberg, S. M., Moretto, L., Sanchez, C., Jambhekar, A., Jensen, M. H., Lahav, G., Entrainment and multi-stability of the p53 oscillator in human cells. (Paper under review for publication)

This is a lecture in the seminar series held by CIM 
(Centre for Interdisciplinary Mathematics).