Mechanisms Underlying the Robustness of Oscillatory Properties

Oscillations occur in many different biological processes, for example as circadian oscillations, in the canonical NF- sciptsize KB-pathway, and calcium signaling. The oscillations can differ in the intensity of their response towards perturbations, the so-called robustness or sensitivity of the particular response. Thereby, the period of calcium oscillations whose function is discussed to lie in frequency encoded signal transduction is known to be very sensitive. Contrariwise, the period of circadian rhythms is very robust; it has to remain nearly unaffected by changes of temperature, pH and nutritional conditions in order to provide reliable timing. A priori, the origins of these differences in period sensitivities are widely unknown. This thesis deals with the effect of system characteristics such as feedback, matter flow properties and kinetics on the period and amplitude sensitivities of oscillating systems. Taking a computational approach, ordinary differential equation models of prototype oscillators are examined for which parameter sets are sampled and sensitivity coeffcients for perturbations of the kinetic parameters are calculated. The detailed analysis shows that besides the feedback type, also matter flow properties and kinetics yield a strong influence on the observed period and amplitude sensitivities. The validity of the results obtained for the prototype oscillators is furthermore examined for published models of calcium and circadian oscillations, and the effect of saturating kinetics is confirmed for models of synthetic oscillators.