CORE: ADMINISTRATION

许多疾病（包括心脏病、糖尿病、癌症和神经系统疾病，如帕金森氏症） 疾病）不能用单一原因/单一效果关系来理解。这是因为虽然 既有基础生理学的深度知识，也有大量的生理和基因组数据， 疾病的动物模型，我们缺乏对多种基因和环境因素如何影响 相互作用以确定表型。我们建议彻底改变我们对复杂表型的理解， 基于系统的多尺度测量、模拟和生理功能分析， 老鼠具体来说，我们建议启动虚拟生理大鼠项目， 用于捕获潜在系统生理学以及相关病理生理学扰动的工具 疾病。这些工具将根据以下方面的实验特性进行开发和验证： 在经过工程改造以显示相关疾病的大鼠品系中， 表型计算机模拟将用于整合不同的数据（基因组，解剖，生理， 等等）。解释和预测功能，并将动物模型的发现转化为新的信息 人类特定的相互关联的复杂疾病，包括高血压，肾脏疾病，心力衰竭， 和代谢综合征。所开发的多尺度生理模型将与基因型表型相联系 参数图来构建虚拟生理大鼠资源，该资源将用于预测 遗传变异和环境因素对表型的影响，并预测表型 新的菌株，将实验衍生和表征。通过系统地和反复地使用 多尺度计算模型，用于分析数据、生成假设、设计实验和预测 表型的新品系的大鼠，我们将获得预测和理解的出现能力， 复杂的特征 除了提议的科学研究的直接影响外，VPR中心将是一个资源， 通过为心血管系统提供独特的软件和相关数据， research.此外，我们还将开发课程、研讨会和相关教育材料，培训和招聘 科学家从服务不足的社区，并举行年度科学会议，为附属和非附属 investigators.

Many diseases (including heart disease, diabetes, cancer, and neurological disorders such as Parkinson's disease) cannot be understood in terms of single-cause/single-effect relationships. This is because although there exist both a depth of knowledge of basic physiology and a host of physiological and genomic data from animal models of disease, we lack an understanding of how multiple genes and environmental factors interact to determine phenotype. We propose to revolutionize our understanding of complex phenotypes and diseases based on systematic multi-scale measurement, simulation, and analysis of physiological function in the rat. Specifically, we propose to initiate The Virtual Physiological Rat Project to develop computational tools to capture the underlying systems physiology as well as the pathophysiological perturbations associated with disease. These tools will be developed and validated based on experimental characterization of physiological function across a number of organ systems in rat strains engineered to show relevant disease phenotypes. Computer simulation will be used to integrate disparate data (genomic, anatomic, physiological, etc.) to explain and predict function, and to translate the findings from animal models to yield new information on specific interrelated complex diseases in humans, including hypertension, kidney disease, heart failure, and metabolic syndrome. The developed multi-scale physiological models will be linked to genotypephenotype parametric maps to construct a Virtual Physiological Rat resource, which will be used to predict the influence of genetic variability and environmental factors on phenotypes and to predict phenotypes of new strains that will be experimentally derived and characterized. By systematically and iteratively using multi-scale computational models to analyze data, generate hypotheses, design experiments, and predict phenotypes in novel strains of rat, we will attain the capability to predict and understand the emergence of complex traits. In addition to the direct impact ofthe proposed scientific studies, the VPR Center will be a resource to the broader community by delivering unique software and associated data for cardiovascular systems research. In addition, we will develop courses, workshops, and related educational material, train and recruit scientists from underserved communities, and hold annual scientific meetings for affiliated and nonaffiliated investigators.