High Performance Computing for Multiscale Modeling of Biological Systems

描述(由申请人提供)：我们建议建立一个生物医学技术研究中心(BTRC)，由匹兹堡大学(PITT；牵头机构)、卡内基梅隆大学(CMU)、匹兹堡超级计算中心(PSC)和索尔克研究所共同努力，进行生物系统多尺度建模的高性能计算。该中心将开发技术和工具，促进计算技术和生命科学之间的研究和培训，并专注于更深入地了解突触信号和调节背后的分子和细胞组织以及机制，从而促进发现治疗神经系统疾病的新方法。其目标是开始填补结构生物学、细胞微生理学和大规模图像分析等不同尺度上的建模努力之间的空白。计算技术研究和开发将在(I)分子建模和模拟、(Ii)细胞建模和模拟以及(Iii)生物图像处理和分析方面进行。这些活动将侧重于开发工具来解决信号传递所固有的空间和分子复杂性，并将由五个实验性生物医学项目(皮特、加州理工大学、哈佛大学和德克萨斯大学西南医学中心)推动，这些项目涉及(I)兴奋性氨基酸转运体的神经递质转运体，(Ii)脊髓中CaMKII的激活，(Iii)多巴胺转运体的多巴胺转运体转运体，(Iv)ITK作为T细胞信号的调节器，以及(Iv)神经元电路重建 连续切片透射式电子显微镜图像。该中心将在其集中地区开展强有力的培训和传播方案，它将利用 PSC是BTRC的总部所在地，已有20多年的历史，除了生物医学技术研究外，还在服务、培训和传播方面有着长期的记录。它还将利用皮特大学计算与系统生物学系和芝加哥大学莱恩计算生物学中心的独特优势，建立在两所大学之间众多成功的合作研究和培训努力的基础上，以及索尔克研究所计算神经生物学实验室的尖端研究。

DESCRIPTION (provided by applicant): We propose to establish a Biomedical Technology Research Center (BTRC) in High Performance Computing for Multiscale Modeling of Biological Systems, as a joint effort between the U of Pittsburgh (Pitt; lead institution), Carnegie Mellon U (CMU), the Pittsburgh Supercomputing Center (PSC) and Salk Institute. The Center will develop technology and tools to facilitate research and training at the interface between computing technology and life sciences, and focus on a deeper understanding ofthe molecular and cellular organization and mechanisms that underlie synaptic signaling and regulation, thus facilitating the discovery of new treatments against nervous system disorders. The goal is to start filling the gap between modeling efforts at disparate scales of structural biology, cellular microphysiology and large scale image analysis. Computational technology research and development (TR&D) studies will be conducted in (i) molecular modeling and simulations, (ii) cell modeling and simulations, and (iii) bioimage processing and analysis. These activities will emphasize developing tools to tackle the spatial and molecular complexity inherent in signal transmission and will be driven by five experimental driving biomedical projects (at Pitt, Caltech, Harvard and UT Southwestern Medical Center) on (i) neurotransmitter transport by excitatory amino acid transporters, (ii) activation of CaMKII in spines, (iii) dopamine transporter trafficking in dopamie neurons, (iv) Itk as a regulator of T cell signaling, and (iv) neuronal circuit reconstruction from serial section transmission electron microscopy images. The Center will carry out a vigorous training and dissemination program in its areas of concentration, it will leverage the capabilities of the PSC which has been home to a BTRC for more than twenty years and, besides its biomedical technology research, has a long track record of service, training and dissemination. It will also take advantage ofthe unique strengths ofthe Computational & Systems Biology Department at Pitt, and the Lane Center for Computational Biology at CMU, building on numerous successful collaborative research and training efforts between the two universities, and cutting-edge research at the Computational Neurobiology Laboratory at the Salk Institute.