Title :
Physiologically based modelling of circadian control on cell proliferation
Author :
Clairambault, Jean
Author_Institution :
INRIA, Rocquencourt
fDate :
Aug. 30 2006-Sept. 3 2006
Abstract :
The molecular circadian clock which is present in almost all cells of animal organisms exerts a control on the cell division cycle in proliferating tissues by modulating the activity of cyclins and cyclin dependent kinases (CDKs), the proteins which determine transitions from one phase of the cell cycle to the following one, until effective division. Each peripheral cell circadian clock is under the synchronising control of a central hypothalamic pacemaker which itself receives inputs, synchronising or disruptive, from external light and from circulating molecules such as cytokines. Principles for modelling these interacting systems are exposed. They rely on age-structured partial differential equations for cell proliferation in a population of cells and ordinary differential equations for the control of cell cycle phase transitions and for the circadian system presented as a network of oscillators with synchronisation and desynchronisation. These physiological cellular systems are coupled together and subject to pharmacological inputs, e.g. from anticancer therapies, which may be synchronised with cell cycle timing by the knowledge of the body circadian clock status, investigated by noninvasive measurements. The output of the controlled cell proliferation is a population growth exponent identifiable by in vivo tissue measurements; it allows to assess the proliferative status of the tissues under investigation, as a function of the circadian clock status, well fit or disrupted, and of pharmacological inputs such as used in anticancer treatments
Keywords :
cancer; cellular biophysics; circadian rhythms; drugs; molecular biophysics; partial differential equations; patient treatment; physiological models; proteins; synchronisation; tumours; age-structured partial differential equations; anticancer therapies; cell cycle phase transition control; cell division cycle control; cell proliferation; central hypothalamic pacemaker; circadian control; cyclin activity; cyclin dependent kinases; cytokines; desynchronisation; molecular circadian clock; noninvasive tissue measurements; peripheral cell circadian clock; pharmacological inputs; physiological based modelling; physiological cellular systems; proteins; synchronisation; tissue proliferation; Animals; Centralized control; Clocks; Lighting control; Organisms; Pacemakers; Partial differential equations; Phase modulation; Proteins; Synchronization;
Conference_Titel :
Engineering in Medicine and Biology Society, 2006. EMBS '06. 28th Annual International Conference of the IEEE
Conference_Location :
New York, NY
Print_ISBN :
1-4244-0032-5
Electronic_ISBN :
1557-170X
DOI :
10.1109/IEMBS.2006.260855