Investigating the Cancer and Aging Link through Systems Biology (CALSYS)

Investigating the Cancer and Aging Link through Systems Biology (CALSYS)

Recent experimental evidences suggest that cancer progression and aging could be linked at the cellular level by the abnormal function of some signalling pathways, cellular systems in charge of identifying and processing the external signals received by the cell. Those mechanisms protect our cells against external or internal insults that damage their genetic material. Leaded by the protein p53, the so-called DNA damage master controller, these processes repair the inflicted DNA damage but also take additional measures to avoid these genetic errors to be transferred to new cells. Depending on the severity of the damage, p53 can trigger a transient/permanent stop of cell replication or the programmed cellular death (apoptosis) in a strategy to kill some damaged cells but save the whole organism. Imbalance between these processes is very often present in different phases of cancer progression, but also is one of the sources of aging in the organism.

The aim of the project is to improve our understanding of the relation between cancer and aging using a systems biology approach. In close relation with experimental biologists, we will create and characterise mathematical models describing cell signalling pathways involved in the DNA damage response in the context of cancer and aging, but we will also investigate how they induce cell senescence and apoptosis.

Our models and the computational methodologies developed in the project will support the generation and experimental test of new hypotheses about the critical processes that make the decision about normal cell growth, senescence or apoptosis. The information generated with our models will be useful to determine therapeutic strategies in cancer, based on drug-mediated modulation of these pathways, but also we will generate new knowledge about the molecular basis of healthy longevity.

The fine tuning in the activation of p53-p21-pRB, p16-pRB, p53-14-3-3sigma and other signalling pathways in response to DNA damage or stress signals play a major role in the induction and maintenance of senescence growth arrest and the decision on whether the cell must undergo cell cycle arrest, senescence or apoptosis.

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