Dynamical Regulation in Physiological Systems

生理系统的动态调节

• 批准号: 8806-2012
• 负责人: Bélair, Jacques
• 金额: $ 1.82万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=568616
• 关键词: Dynamical; Regulation; Physiological; Systems

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).

许多生理现象表现出复杂的波动。这种变异性可以作为个体健康状况的指标，例如心率、睡眠-觉醒周期的波动或胃肠道平滑肌收缩。近年来，将生理系统实验研究与生理动力学理论模型相结合的研究为某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小心和精确，以获得足够详细的数据，以便与理论观察进行比较，从而提出新的理论（建模）方法。 对于以下生理系统，我们将开发数学模型，以实现足够简化的表示，以便对整个系统进行深入的理解，但又足够复杂，可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，并探索与主要控制其他血细胞类型（白细胞、血小板）调节的其他机制的相互作用。 2) 最近开发了新药开发的新框架和更优化的给药方法：“建模和模拟”现在是新药理学的基础，它利用计算能力来设计“计算机模拟”实验。我们将采用这种概念方法，将生理机制的数学表示与统计估计相结合，以便在生物体水平上更好地理解如何使某些化疗药物对免疫系统（中性粒细胞）产生更少的副作用。