High Performance Computing for Multiscale Modeling of Biological Systems

描述（由申请人提供）：我们建议建立生物系统多尺度建模高性能计算生物医学技术研究中心（BTRC），由匹兹堡大学（皮特；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。该中心将开发技术和工具，以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和机制，从而促进发现针对神经系统疾病的新疗法。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的建模工作之间的空白。计算技术研究和开发（TR&D）研究将在(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中进行。这些活动将强调开发工具来解决信号传递中固有的空间和分子复杂性，并将受到五个实验性生物医学项目（在Pitt， Caltech， Harvard和UT Southwestern Medical Center）的推动(i)兴奋性氨基酸转运体的神经递质运输，（ii）脊髓中CaMKII的激活，（iii）多巴胺转运体在多巴胺神经元中的运输，（iv） Itk作为T细胞信号的调节剂，（iv）神经回路重建

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.