Collaborative Research: Systems-wide Spatiotemporal Patterning in Itk Function

细胞是生命的基本单位。它们通过接收外部信号并处理这些信号来调节细胞行为。信号处理是一个复杂的过程，涉及数十甚至数百个细胞成分（称为信号中间体），它们必须相互作用以调节细胞行为。每个细胞内这种信号中间体的数量随接收到外部信号后的时间和它们在细胞中的位置的函数而变化。这些共同被称为时空模式。时空模式对于理解活细胞中的信号传导效率至关重要，因为在同一位置同时富集两种蛋白质会增加它们相互作用的可能性，即它们的效率。因此，如果我们要解开数十到数百个信号中间体的复杂相互作用网络，了解时空模式是必不可少的，这是当前生物学中的一个巨大挑战。该项目的目标是：1)在不同的细胞激活条件下获取许多蛋白质信号中间体的比较图像数据集，并开发和应用图像分析方法来准确定义细胞（T淋巴细胞）内信号中间体的数量和位置。此外，这些方法将用于定义这些信号中间体的数量和位置如何随着T细胞对不同刺激的反应而随时间变化。2)由于本项目将开发的数据和方法将对理解蜂窝信号具有普遍的兴趣和价值，因此它们将在服务器上公开提供。其他研究人员将有机会使用这些方法来分析他们的图像数据。T细胞显微镜实验将为合作者执行，成像数据的视觉吸引力将用于丰富高中教育。更广泛的影响：除了向研究界提供即将开发的资源和数据外，该项目还将吸引高中生、研究生和医学院学生，以及两名博士后。来自美国各地的本科生将有机会通过德克萨斯大学西南夏季本科生研究奖学金项目（该项目强调招募未被充分代表的少数民族）参与该项目。墨菲博士将通过卡内基梅隆大学的本科生研究经验项目培训和指导少数民族学生。

Cells are the basic units of life. They function by receiving signals from the outside and processing these signals to regulate cellular behavior. Signal processing is a complex process involving tens if not hundreds of cellular components (referred to as signaling intermediates) that must interact with each other to regulate cellular behavior. The amounts of such signaling intermediates inside each cell vary as a function of time after receiving a signal from the outside and as a function of their location in the cell. Jointly, these are referred to as spatiotemporal patterns. Spatiotemporal patterns are critical for understanding signaling efficiency in live cells, as enrichment of two proteins in the same location at the same time increases the likelihood that they will interact, i.e. their efficiency. Thus, an understanding of spatiotemporal pattering is essential if we are to unravel the complex interaction network of tens to hundreds of signaling intermediates, a great challenge in current biology. The goals of this project are: 1) To acquire comparative image data sets on many protein signaling intermediates under varying conditions of cellular activation and to develop and apply image analysis methods to accurately define the amount and location of the signaling intermediates within a cell (the T lymphocyte). In addition, these methods will be applied to define how the amount and location of these signaling intermediates vary with time as T cells respond to the different stimuli. 2) Because the data and methods that will be developed in this project will be of general interest and value for understanding cellular signaling, they will be made publicly available on servers. Other investigators will be given the opportunity to use these methods to analyze their image data. T cell microscopy experiments will be executed for collaborators, and the visual appeal of imaging data will be used to enrich high school education. Broader impacts: In addition to providing the research community access to the resources and data that will be developed, this project will engage high school, graduate and medical students, as well as two postdoctoral fellows. Undergraduate students from around the US will be given opportunities to work on this project through the University of Texas Southwestern Summer Undergraduate Research Fellowship program (which places an emphasis on recruiting underrepresented minorities). Dr. Murphy will train and mentor minority students through a Research Experiences for Undergraduates program at Carnegie-Mellon University.