Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

Modeling circadian clock-cell cycle interaction effects on cell population growth rates
Raouf El Cheikh, Samuel Bernard, Nader El Khatib

Last modified: 2014-03-28


The circadian clock regulates many daily rhythmic activities in the human body, from the wake-sleep phases succession and hormone production to blood pres- sure and body temperature. Several epidemiological studies have shed light on the fact that disruption of circadian rhythms leads to abnormal proliferation of cells and could enhance tumor development. The circadian clock and the cell cycle are tightly connected. In this work we present a mathematical model that combines both intracellular and population levels and studies the coupling of the cell cycle with the circadian clock through the protein WEE1. We study the effect of coupling on the period of cell cycle division. We show that for certain combinations of coupling strength and autonomous periods, the cell cycle can entrain to the circadian clock with a rational period ratio, referred to as n:m phase locking or entrainment. Then we investigate the influence of coupling on the growth rate for autonomous periods of the cell cycle varying from 8 to 60 hours. We show that coupling in- creases the growth rate when the autonomous period of the cell cycle is between 21 and 30 hours and decreases it elsewhere. The results also show that in some cases, even though the cell cycle slows down, the growth rate can still increase. We also study the effect of mutation of circadian genes on the growth rate of cells and show that disruption of the circadian clock can lead to abnormal pro- liferation. Particularly, we show that Cry1, Cry2 mutations decrease the growth rate of cells, Per2 mutation enhances it and Bmal1 knockout increases it for au- tonomous periods of the cell cycle less than 21 hours and decreases it elsewhere.


circadian clock; cell-cycle; age-structured equations