STRUCTURALLY & FUNCTIONALLY INTEGRATED MODELING OF CELL & ORGAN BIOPHYSICS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 总的目标是开发和部署新颖的、可上网的、支持集群的、具有网格意识的软件和数据资源，使生物力学、生物物理学和心血管生理学的研究人员能够进行以下数值实验：从亚细胞到整个器官的结构一体化；跨相互作用的生物过程的功能一体化；以及综合来自各种来源、尺度和模式的实验数据。 我们将探索和推进这些综合分析的合成，以便研究人员可以开发计算模型，在功能和结构上将理论与经验数据相结合，以研究实验动机的生物医学假说。为了实现这些目标，我们建议与可视化、网格计算和数据集成的核心研究活动密切互动的资源。为了将这些发展集中在科学上的重要问题上，我们与研究人员开发了合作项目，这些研究人员正在应用实验和计算方法来了解生理和病理生理过程的细胞和分子机制，这些过程依赖于整个心脏的三维解剖，以获得其在体内的表现。 这一核心的主要应用将继续是心脏机电特性的计算模型，该模型集成了从单个心肌细胞生物物理学到整个心脏生理学，并在具有良好特征的动物模型中通过实验测量进行验证。虽然这些多尺度模型的数据成分及其实验验证是特定于心脏的，但计算方法和软件更为通用。因此，更新的目标和正在开发的新工具的目标用户超越了心脏的生物物理学，扩展到其他生物医学应用，包括软组织生物力学、电生理学、系统生物学和诊断医学成像。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall objective is to develop and deploy novel, web accessible, cluster-enabled, grid-aware software and data resources that allow investigators in biomechanics, biophysics and cardiovascular physiology to perform numerical experiments that are: structurally integrated from sub-cellular to whole organ scales; functionally integrated across interacting biological processes; and that integrate experimental data from a variety of sources, scales and modalities. We will explore and advance the synthesis of these integrative analyses so that investigators can develop computational models that integrate theory with empirical data both functionally and structurally to investigate experimentally motivated biomedical hypotheses. To achieve these goals, we propose to interact closely with the visualization, grid computing and data integration core research activities of the resource. To focus these developments on scientifically important questions, we have developed collaborative projects with investigators who are applying experimental and computational approaches to understand the cellular and molecular mechanisms of physiological and pathophysiological processes that are dependent on the three-dimensional anatomy of the whole heart for their manifestations in vivo. The primary application of this core will continue to be computational models of cardiac electromechanical properties that integrate from single myocyte biophysics to whole heart physiology and are validated with experimental measurements in well characterized animal models. Whereas the data components of these multiscale models and their experimental validation are specific to the heart, the computational methods and software are more general. Therefore, the aims of the renewal and the targeted users of the new tools under development extend beyond the biophysics of the heart to other biomedical applications including soft tissue biomechanics, electrophysiology, systems biology, and diagnostic medical imaging.