Circadian and cell cycle clock systems in cancer – ERASYsBIO (ANR-09-SYSB-0002)

Mammalian cells are endowed with biological oscillators which time their activities. The circadian clock (circa, about; dies, day) generates a 24-hour rhythm which controls both cellular metabolism and cell division. The cell division cycle is an oscillator which times DNA synthesis, mitosis, and related apoptosis and DNA repair. Our understanding of the molecular mechanisms at work in both oscillators has greatly improved. In sharp contrast, little is known about how these two crucial oscillators interact, and how these interactions affect cellular proliferation in normal or cancer cells. On the one hand, the disruption of circadian clocks impairs cell physiology and quality of life. On the other hand, disruption of cell cycle, DNA repair or apoptosis impacts on cell and organism survival. Experimental and clinical data show that circadian disruption accelerates malignant proliferation, and that DNA damage can reset the circadian clock. The central question addressed is how interactions between the circadian clock and cell cycle affect cellular proliferation and genotoxic sensitivity in normal and cancer cells, and how this knowledge translates into new prevention or therapeutic applications. Seven teams in France, Netherlands and United Kingdom integrate experimental, mathematical and bioinformatic approaches, so as to develop novel cell lines, biomarker monitoring methods and mathematical tools. C5Sys triggers innovative chronotherapeutic research for human cancers and advances systems medicine for improving patient care.