MSM: Multi-scale modeling of the mouse heart: from genotype to phenotype

这项研究的目的是开发新的小鼠心脏的多尺度计算模型，该模型在功能和结构上整合了从分子网络到器官系统的多个尺度的生物组织。这些新的正常和转基因小鼠心脏的电力学模型将整合以下生物学尺度和数学模型类别：(1)分子调控网络的生化模型；(2)整个兴奋-收缩耦合的生物物理模型；(3)多细胞心脏组织区域各向异性电力学性能的微结构本构模型；(4)小鼠心室几何、纤维结构和传导系统解剖的三维解剖细节模型；(5)循环系统血流动力学集总参数模型。这项研究将更好地理解正常的心脏，以及它在病理生理状态下如何变得功能失调。这项拟议中的研究将在加州大学圣地亚哥分校的生物工程师和南卡罗来纳大学的发育生物学家和解剖学家之间发起一项新的跨学科合作。这次合作的结果是，一个新的大型多尺度数据资源将使科学家能够以高分辨率导航整个小鼠心脏解剖。

McCulloch0506252The aim of the research is to develop new multi-scale computational models of the mouse heart that integrate functionally and structurally across multiple scales of biological organization from molecular networks to organ system. These new models of the electromechanics of the normal and genetically modified mouse heart will integrate across the following biological scales and classes of mathematical model: (1) biochemical models of molecular regulatory networks; (2) biophysical models of whole excitation-contraction coupling; (3) microstructural constitutive models of the regional anisotropic electrical and mechanical properties of multicellular cardiac tissue; (4) three-dimensional anatomically detailed models of mouse ventricular geometry, fiber architecture and conducting system anatomy; and (5) lumped parameter models of circulatory system hemodynamics. This research will provide better understanding of the normal heart and how it becomes dysfunctional in pathophysiological states.The proposed research will initate a new inter-disciplinary collaboration between bioengineers at University of California San Diego and developmental biologists and anatomists at University of South Carolina. As a result of this collaboration, a large new multi-scale data resource that will allow scientists to navigate whole mouse heart anatomy at high resolution.