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，从分子网络到器官系统，跨生物组织的多个尺度在功能和结构上进行集成。这些新的正常和转基因小鼠心脏的机电模型将集成在下列生物尺度和数学模型类别中：(1)分子调控网络的生化模型；(2)整体兴奋-收缩耦合的生物物理模型；(3)多细胞心脏组织局部各向异性电和机械特性的微观本构模型；(4)小鼠心室几何、纤维结构和传导系统解剖的详细三维解剖模型；以及(5)循环系统血流动力学的集中参数模型。这项研究将更好地了解正常心脏以及它如何在病理生理状态下变得不正常。这项拟议的研究将引发加州大学圣地亚哥分校的生物工程师与南卡罗来纳大学的发育生物学家和解剖学家之间的一项新的跨学科合作。作为这项合作的结果，一个大型的新的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.