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

理解和操纵细胞行为的能力目前是有限的。在这个项目中，这是一个合作的研究人员在麦基-梅隆大学（美国）和布里斯托大学（英国），开源计算工具将被开发，将允许活细胞（T淋巴细胞）的显微图像，介导免疫反应被转换成计算机模型。这些模型将从显微图像中捕获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，从而详细了解控制T细胞免疫反应的机制。将为研究生和本科生（包括在科学中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，并为K-12学生制作旨在促进STEM领域兴趣的开放获取电影。这些电影将通过与主要为代表性不足的少数民族学生服务的爱丁堡地区学校合作开发。捕获蛋白质荧光图像的电影（以及全细胞蛋白质磷酸化的测定）将用于开发开源软件工具，这些工具将生成和解释参与T淋巴细胞信号传导的35个关键分子的时空对齐图。时空图将被用于推断潜在的信号复合物，以及参与T淋巴细胞信号传导的蛋白质之间的表观亲和力和潜在的因果关系。这个美国/英国合作项目得到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.