Dynamical Regulation in Physiological Systems

许多生理现象都表现出复杂的波动。这种变异性可以作为个体健康的指标，例如心率、睡眠-觉醒周期的波动或胃肠道轨道上的平滑肌肉收缩。近年来，将生理系统的实验研究与生理动力学的理论模型相结合的研究为一些心脏和血液疾病的机制提供了新的见解。进行适当的实验需要非常谨慎和精确，以便获得足够详细的数据，以便与理论观测进行比较，理论观测反过来又提出了新的理论(建模)方法。 对于下面的生理系统，我们将开发数学模型，以使表示法足够简单，以允许对系统作为一个整体进行重要的理解，但又足够复杂，以包含生理学的所有基本组成部分。 1)循环血细胞的调节是一个复杂的生化系统。我们研究了主要调节蛋白促红细胞生成素在将红细胞数量维持在适当水平的反馈机制中的影响，并探索了与其他主要控制其他血细胞类型(白细胞、血小板)调节的机制的相互作用。 2)最近开发了一种新的开发新药的框架和更优化的管理方法：“建模和模拟”现在是新的药物计量学科学的基础，它利用计算能力的可用性来设计“在Silico”的实验。我们将采用这种概念性的方法，它将生理机制的数学表示与统计估计相结合，以在有机体的水平上更好地理解一些化疗药物如何使其对免疫系统(中性粒细胞)产生较少的副作用。

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).