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

目前，理解和操纵细胞行为的能力是有限的。在这个由美国卡内基-梅隆大学和英国布里斯托尔大学的研究人员合作的项目中，将开发开放源代码的计算工具，允许将介导免疫反应的活细胞(T淋巴细胞)的显微图像转换为计算机模型。这些模型将从显微图像中捕捉构成信号通路和网络的蛋白质的行为，这些信号通路和网络是细胞行为的基础和控制，从而详细了解T细胞免疫反应的控制机制。将向研究生和本科生(包括在科学方面代表性不足的群体的成员)提供细胞生物学和计算机科学的跨学科培训，并将为K-12学生制作旨在促进对STEM领域的兴趣的开放获取电影。这些电影将通过与匹兹堡地区的学校合作开发，这些学校主要为少数族裔学生提供服务。捕捉蛋白质荧光图像(以及细胞内蛋白质磷酸化的测定)的电影将被用于开发开源软件工具，这些工具将生成并解释参与T淋巴细胞信号传递的35个关键分子的时空排列地图。时空图将被用来推断潜在的信号复合体，以及参与T淋巴细胞信号的蛋白质之间的表观亲和力和潜在的因果关系。这项美英合作项目得到了美国国家科学基金会和英国生物技术和生物科学研究理事会的支持。

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.