PROJECT 4

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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