Bilateral BBSRC-NSF/BIO: Causal modeling of T cell signaling in time and space

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The ability to understand and manipulate the behavior of cells is currently limited. In this project, which is a collaboration between researchers at the Carnegie-Mellon University (US) and the University of Bristol (UK), open source computational tools will be developed that will permit microscopic images of live cells (T lymphocytes) that mediate immune responses to be converted into computer models. These models will capture from the microscopic images the behavior of the proteins that constitute the signaling pathways and networks that underlie and control the behavior of the cells, producing a detailed understanding of the mechanisms by which T cell immune reactions are controlled. Interdisciplinary training in cell biology and computer science will be provided to graduate and undergraduate students (including members of groups underrepresented in science), and open access movies designed to promote interest in STEM fields will be produced for K-12 students. These movies will be developed through partnerships with Pittsburgh-area schools serving primarily students from underrepresented minorities. Movies capturing fluorescence images of proteins (and determination of cell-wide protein phosphorylation) will be used to develop open source software tools that will generate and interpret spatiotemporally aligned maps of 35 key molecules involved in T lymphocyte signaling. The spatiotemporal maps will be used to infer potential signaling complexes, and the apparent affinities and potential causal relationships amongst proteins involved in T lymphocyte signaling.This collaborative US/UK project is supported by the US National Science Foundation and the UK Biotechnology and Biological Sciences Research Council.