Cytoskeleton polymerization dynamics in the cell cycle

Harvard Medical School, Boston MA

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Abstract

DESCRIPTION (provided by applicant): We will generate a catalog of biochemical changes that occur on the surface of cancer during cell division (mitosis and cytokinesis) and during programmed cell death (apoptosis). We will obtain these data by labeling the surface of cultured cells that have been synchronized using drugs, isolating plasma membrane proteins, and then comparing different cell states by a quantitative, comparative mass spectrometry method called SILAC. Our catalog will allow us to identify cell-surface biomarkers for mitotic arrest and apoptosis, and we will generate antibodies that recognize these biomarkers. These biomarkers will be very useful for understanding why some cancers are resistant to anti-mitotic cancer drugs such as paclitaxel, and learning how to combat that resistance. Our catalog will also open new avenues in cell cycle research, since there have been no systematic studies of how the cell cycle regulates the cell surface since the 1970s. PUBLIC HEALTH RELEVANCE: We will use mass spectrometry to discover proteins or protein modifications on the cell surface that are selective for dividing or dying cells. These will provide biomarkers for understanding how anti-mitotic drugs work or fail in cancer therapy, as well as opening new avenues in cell cycle research.