SysDamSen: Systems biology of DNA-damage induced premature cellular senescence

Cellular senescence is generally defined as an irreversible state of G1 cell cycle arrest in which cells are refractory to growth factor stimulation.

Cellular senescence can be induced through several different mechanisms like oncogenic, mitogenic signals as well as DNA damage. DNA damage can cause stress-induced premature senescence (SIPS), opposed to replicative senescence, which occurs in all non-transformed proliferating cells due to telomere shortening. In this project, we want to come to a quantitative understanding of the dynamic processes involved in control and regulation of premature DNA-damage induced senescence. We study normal human fibroblasts (MRC-5, BJ) treated with ionising radiation to induce cellular senescence by analysing the dynamics of signalling pathways involved in regulation of cell cycle arrest and cellular senescence. Based on these results, we establish a mathematical model of the DNA damage response and associated processes involved in the establishment of the senscence phenotype. This model will be used to optimise further experiments hence extending our knowledge and better understanding of the regeneration processes and ageing.