System Biology Center in New York

描述（由申请人提供）：纽约系统生物学中心（NYCSB）汇集了来自西奈山SOM、哥伦比亚大学内科医学院、纽约大学数学科学学院、纽约州立大学石溪分校、城市学院和IBM t.j. Watson研究实验室，整合理论和实验方法，深入了解哺乳动物生理/病理生理系统的多尺度功能组织，以及药物（治疗性和滥用性）如何影响该组织。我们想了解分子相互作用的影响是如何在组织的各个尺度上传播的，从细胞到组织和器官，影响生理和病理生理。我们假设，多尺度网络中基序（调控回路）的动态组织为从分子到细胞到组织的跨尺度效应传播提供了基础。药物通过在这些尺度上重新组织网络拓扑来发挥作用。我们研究心脏和大脑的特定过程来验证这些假设。我们正在开发和无缝集成多种建模方法，包括图论分析，基于微分方程的建模和随机反应扩散的新方法，以模拟三维过程。这样的理论整合使我们能够构建和分析多尺度模型。我们正在开发在IBM Blue-Gene/L等超级计算机上运行的并行程序，用于大型网络中的动态基序搜索和基于微分方程的模型模拟。理论研究与多变量实验相结合，通过反向蛋白阵列、转录因子阵列和微阵列分析活性变化。多变量实验反过来又与分子相互作用的定量测量和组织水平的生理测量相结合，以约束模型和测试模型预测。NYCSB的研究活动与我们的教育和推广活动形成了一个连续体，包括研究生和博士后培训，针对本科生的暑期项目，重点是招募代表性不足的少数民族，培训本科教育工作者，个性化研讨会以及为所有研究人员参与NYCSB研究项目的机会。这些研究、教育和推广活动将使NYSBC为系统医学和治疗学的发展做出重大贡献。

DESCRIPTION (provided by applicant): The New York Center for Systems Biology (NYCSB) brings together researchers and educators from Mount Sinai SOM, Columbia University College of Physicians, Courant Inst of Mathematical Sciences NYU, SUNY Stony brook, City College CUNY and the IBM T.J Watson Research Lab to integrate theoretical and experimental approaches for a deep mechanistic understanding of multi-scale functional organization of mammalian physiological/pathophysiological systems and how drugs (therapeutic and abusive) affect this organization. We want to understand how the effects of molecular interactions are propagated across scales of organization from cells to tissues and organs affecting physiology and pathophysiology. We posit that the dynamic organization of motifs (regulatory loops) within multi-scale networks provides the basis for propagation of effects across scales from molecules to cells to tissues. Drugs have their effects by reorganizing network topology across these scales. We study selected processes in the heart and brain to test these hypotheses. We are developing and seamlessly integrating multiple modeling approaches including graph theory analysis, differential equation-based modeling and the new method of stochastic reaction-diffusion to model processes in 3D. Such theoretical integration allows us to construct and analyze multi-scale models. We are developing parallelized programs that run on supercomputers such as IBM Blue-Gene/L both for dynamic motif searches in large networks and for simulations of differential equation- based models. The theoretical studies are well integrated with multivariable experiments to profile activity changes by reverse protein arrays, transcription factor arrays and microarrays. The multivariable experiments in turn are combined with quantitative measurements of molecular interactions and tissue level physiological measurements to constrain models and test model predictions. The research activities of the NYCSB form a continuum with our educational and outreach activities that include graduate and postdoctoral training, summer programs for undergraduates with a focus on recruiting underrepresented minorities, training undergraduate educators, personalized workshops and opportunities to participate in the NYCSB research projects for all researchers. Together these research, education and outreach activities will allow NYSBC make significant contributions towards the development of Systems Medicine and Therapeutics.