Cytoskeleton polymerization dynamics in the cell cycle

描述(申请人提供)：我们将生成一个在细胞分裂(有丝分裂和胞质分裂)和细胞程序性死亡(细胞凋亡)期间发生在癌症表面的生化变化的目录。我们将通过标记使用药物同步化的培养细胞的表面，分离质膜蛋白，然后用一种名为SILAC的定量、比较质谱学方法比较不同的细胞状态，来获得这些数据。我们的目录将使我们能够识别细胞表面有丝分裂停滞和凋亡的生物标记物，我们将产生识别这些生物标记物的抗体。这些生物标记物将非常有助于理解为什么一些癌症对紫杉醇等抗有丝分裂癌症药物具有耐药性，并了解如何对抗这种耐药性。我们的目录还将为细胞周期研究开辟新的途径，因为自20世纪70年代以来，一直没有关于细胞周期如何调节细胞表面的系统研究。 与公共健康相关：我们将使用质谱学来发现细胞表面的蛋白质或蛋白质修饰，这些蛋白质或蛋白质修饰对细胞分裂或死亡具有选择性。这些将为了解抗有丝分裂药物在癌症治疗中的作用或失败提供生物标记物，并为细胞周期研究开辟新的途径。

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.