Center for Modeling Integrated Metabolic Systems (MIMS)

描述(由申请人提供)：要定量了解细胞代谢与组织、器官和全身过程相结合的复杂性，需要复杂的数学模型、计算机模拟和实验数据验证。基于生理的模型包含了大量化学物质的细胞代谢反应和运输过程。一般而言，这些空间集中和/或分布式系统的动态模型涉及高度非线性现象。这样的模型可以定量评估疾病状态下正常和异常条件下的代谢途径和调节机制。因此，这些模型可以为模拟药物改变酶含量/活性或底物浓度的综合效应提供基础。对于这种复杂的生物医学系统的研究，我们提出了一个集成代谢系统建模中心(MIMS)。 MIMS中心的重点将是对代谢系统进行数学建模和模拟，以应对与低氧、运动和饮食输入相关的压力。一个全面的整体模型将在四个主要的组织器官系统中将细胞和组织的代谢联系起来：骨骼肌、脑、头和肝脏。生物医学研究项目将纳入一种或多种代谢压力，其中建模可以帮助量化机制并预测无法直接测量的反应。这些项目将包括对器官内细胞-组织整合的建模，以及对组合的组织-器官系统的整合的全身影响的建模。将进行关键的实验研究，以进行模型验证。除了这些项目领域，该中心还将有两个核心处理与建模相关的研究：系统建模集成和大型动态系统的计算方法。另外两个核心将支持MIMS中心的任务：基于网络的公共信息网站以及研究、培训和教育。MIMS中心的主要所在地凯斯西储大学和克利夫兰州立大学将建立合作伙伴关系，克利夫兰州立大学在本科课程中有大量代表不足的少数族裔。

DESCRIPTION (provided by applicant): A quantitative understanding of the complexity of cellular metabolism integrated with tissue, organ, and whole-body processes requires sophisticated mathematical models, computer simulations, and validation with experimental data. Physiologically based models incorporate cellular metabolic reactions and transport processes of a large number of chemical species. In general, these dynamic models of spatially lumped and/or distributed systems involve highly nonlinear phenomena. Such models allow quantitative evaluation of metabolic pathways and regulatory mechanisms under normal and abnormal conditions in disease states. Consequently, these models can provide a basis for simulating the integrated effects of altering enzyme contents/activities or substrate concentrations with pharmacological agents. For this complex biomedical systems research, we propose a Center for Modeling integrated Metabolic Systems (MIMS). The thrust of the MIMS Center will be mathematical modeling and simulation of metabolic systems in response to stresses associated with hypoxia, exercise, and dietary inputs. A general integrative whole-body model will relate cellular to tissue metabolism in four major tissue-organ systems: skeletal muscle, brain, head, and liver. Biomedical research projects will incorporate one or more of the metabolic stresses in which the modeling can help quantify mechanisms and predict responses that cannot be directly measured. These projects will involve modeling of cell-tissue integration within an organ as well as modeling the integrated, whole-body effects of the combined tissue-organ systems. Critical experimental studies will be conducted for model validation. In addition to these project areas, the Center will have two cores that deal with modeling related research: Systems Modeling Integration and Computational Methods for Large Scale Dynamic Systems. Two other cores will support the missions of the MIMS Center: Web-Based Public information Site, and Research Training and Education. A partnership will be established between Case Western Reserve University, the primary site of the MIMS Center, and Cleveland State University, which has a substantial number of under-represented minorities in undergraduate programs.