Dynamical Regulation in Physiological Systems

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Many physiological phenomena show complex fluctuations. This variability can be an index of the health of the individual, as in the case of the heart rate, fluctuations in sleep-wake cycle or smooth muscle contractions in the gastro-intestinal track. In recent years, research combining experimental studies of physiological systems with theoretical models of physiological dynamics has provided new insight into the mechanisms responsible for some cardiac and hematological disorders. Carrying out the appropriate experiments requires great care and precision in order to obtain data sufficiently detailed to be compared with theoretical observations which in turn suggest new theoretical (modeling) approaches. For the following physiological systems, we will be developing mathematical models thriving for a representation that is simplified enough to allow for significant understanding of the system as a whole, yet is complex enough to incorporate all the fundamental components of the physiology. 1) The regulation of the circulating blood cells is a complex biochemical system. We study the influence of the main regulatory protein, erythropoietin, in the feedback mechanism maintaining the number of red blood cells at an appropriate level, and explore the interactions with other mechanisms predominantly controlling the regulation of other blood cell types (white blood cells, platelets). 2) A new framework for the development of new drugs and more optimal means of administrating them has recently been developed: "Modelling and Simulation" are now the basis of the new science of pharmacometrics, which exploits the availability of computing power to devise experiments "In Silico". We will employ this conceptual approach, which combines mathematical representations of physiological mechanisms to statistical estimation to better understand, at the level of the organism, the way in which some chemotherapeutic agents could be made to have less side effects on the immune system (neutrophils).