Study of dynamics of T cell signaling published in Science Signaling

Cells often need to respond to signals received through surface receptors, and their responses involve changes in the spatial arrangement of proteins with the cell.  For example, T cells receive signals through the T cell receptor (TCR) to indicate the presence of a particular antigen that they should respond to, and an additional signal through a costimulatory receptor (CD28) is required for them to respond fully.

Changes in individual proteins within the T cell can be imaged using fluorescence microscopy, but variability from cell to cell and noise in the images make it difficult to understand the sequence of events that are occurring. Dr. Murphy’s group in the Computational Biology department developed computational methods to address this problem, collaborating with the group of Dr. Christoph Wülfing at the University of Bristol who imaged fluorescently-tagged signaling proteins in T cells activated through the TCR in the absence or presence of CD28 signaling. The results, described in a paper published today in Science Signaling, are detailed “maps” of the concentration of nine proteins over time following stimulation.  The computational analysis method could be combined with imaging of other signaling systems to provide more detailed understanding of their dynamics.  The work was part of the activities of the NIH-supported National Center for Multiscale Modeling of Biological Systems.