PROJECT 10

麻省理工学院细胞决策过程中心(CDP Center；www.cdpcenter.org)应用修饰测量模型范式来研究人类细胞中受体介导的死亡和生存信号。肿瘤坏死因子受体、TRAIL和Fas死亡受体下游的促凋亡和炎症通路以及由六个相互作用的ErbBl-4、IGF-1和cMET生长因子受体以及T细胞受体激活的促存活和促有丝分裂通路特别令人感兴趣。该中心的主要目标是使用从统计到物理化学的各种方法建立信号转导的数学模型。所有模型都包含了经验数据，并经过了严格的实验验证。为了收集和系统化训练和测试模型所需的数据，该中心开发了新的质谱学、微系统和成像方法，以及连接数据和模型的软件。教育、外联和社区发展是该中心的核心活动，它将继续支持各种活动，包括为高中生开设的暑期课程，为来自少数族裔服务机构的知名科学家和工程师提供的休假，系统生物学的国际会议和它建立的跨学科社区，包括麻省理工学院的CSBI和波士顿的系统生物学理事会。CDP将在其研究成功的基础上，通过一个由五部分组成的计划，强调(1)在可访问的细胞培养系统中构建、校准和验证哺乳动物信号过程的模型，(2)开发新的实验方法，通过基于阵列的测量从小细胞群和单细胞中收集定量和动态数据，开发微流体设备和新的活细胞成像方法，(3)强调专门细胞的系统生物学，因为它适用于初级T细胞、人类肝细胞和人类中性粒细胞，以及炎症性疾病和癌症中健康和疾病状态的差异，(4)继续发展电子化的研究核心和信息技术，特别是那些加强数据共享和协作的研究核心和信息技术；以及(5)通过影响广泛的平衡方案和那些有可能极大提高个人职业生涯的方案，继续致力于推广和教育

The Center for Cell Decision Processes at MIT (CDP Center; www.cdpcenter.org) applies a modiry-measuremine- model paradigm to study receptor-mediated death and survival signaling in human cells. Pro-apoptotic and inflammatory pathways downstream of TNF, TRAIL and Fas death receptors are of particular interest, as are the pro-survival and mitogenic pathways activated by the six interacting ErbBl-4, IGF-1 and cMet growth factor receptors and by the T-cell receptor. The primary goal of the Center is to build mathematical models of signal transduction using a variety of methods ranging from statistical to physicochemical. All models incorporate empirical data and are subjected to rigorous experimental validation. To collect and systematize the data necessary to train and test models, the Center develops new mass spectrometry, microsystems and imaging methods as well as software to link data and models. Education, outreach and community development are core activities of the Center, and it will continue to support activities ranging from summer courses for high school students to sabbaticals for established scientists and engineers from minority-serving institutions, international conferences in systems biology and interdisciplinary communities it has established including CSBi at MIT and the Council for Systems Biology in Boston. CDP will build on its success in research through a five-part program that stresses (1) construction, calibration and validation of models of mammalian signaling processes in accessible cell-culture systems, (2) development of new experimental methods to gather quantitative and dynamic data from small cell populations and single-cells via array-based measurement, development of microfluidic devices and new approaches to live-cell imaging, (3) an emphasis on the systems biology of specialized cells, as it applies to primary T-cells, human hepatocytes and human neutrophils and to differences between healthy and diseased states in inflammatory disease and cancer, (4) continued development of electronically enabled research cores and information technologies, particularly those that enhance data sharing and collaboration, and (5) continued commitment to outreach and education through balanced programs with broad impact and those with the potential to substantially enhance individual careers