Regensburg 2019 – wissenschaftliches Programm
AKjDPG 3: PhD Focus Session: Theory of Stochastic Processes with Applications in Biology (joint session SOE/BP/DY/AKjDPG)
AKjDPG 3.8: Vortrag
Donnerstag, 4. April 2019, 18:30–18:45, H17
Beating cancer 'escape room': let's use mathematical modelling to unlock cells! — •Núria Folguera-Blasco — The Francis Crick Institute, London, UK
The inherent capacity of differentiated cells to switch their phenotype in vivo in response to damage stimuli might have a pivotal role in ageing and cancer. However, how the mechanisms of phenotype reprogramming are established remains poorly understood. In order to elucidate such mechanisms, we present a stochastic model of combined epigenetic regulation (ER)-gene regulatory network (GRN) to study the plastic phenotypic behaviours driven by ER heterogeneity. Our analysis of the coupled system reveals the existence of pluripotent stem-like and differentiated steady-states. Crucially, ER heterogeneity is responsible for conferring abnormal robustness to pluripotent stem-like states, which cause the locking of the cells in a stem cell-like state prone to cancer development. By analysing the ER heterogeneity, we formulate epigenetic heterogeneity-based strategies capable of unlocking and facilitating the transit from differentiation-refractory (pluripotent stem-like) to differentiation-primed epistates. Our results suggest that epigenetic heterogeneity regulates the mechanisms and kinetics of phenotypic robustness of cell fate reprogramming. The occurrence of tunable switches capable of modifying the nature of cell fate reprogramming from pathological to physiological might pave the way for new therapeutic strategies to regulate reparative reprogramming in ageing and cancer.