Spatiotemporal Control of Migratory Cellular Behavior

项目摘要 人们对确定促进肿瘤脑内侵袭的生化途径非常感兴趣，因为 这些通路的成员是潜在的治疗靶点。不幸的是，宇宙的时空本质 这些途径提供了常规工具的应用(目的蛋白的过表达/过表达， 抑制性化合物等)不足以研究细胞的动态行为。我们寻求设计和评估 COFILIN的光遗传学类似物，COFILIN的上游激活物(弹弓和计时蛋白)，以及COFILIN的上游 负性调节因子(LIM蛋白激酶、cAMP依赖的蛋白激酶、p21活化的蛋白激酶、 和Rho相关蛋白激酶)。这些物种提供了一种手段来关联空间上聚焦的生化 具有动态细胞行为的活性，包括F-肌动蛋白重塑活性以及迁移和侵袭 才能。

Project Summary There is keen interest in identifying the biochemical pathways that promote tumor intracerebral infiltration since members of these pathways serve as potential therapeutic targets. Unfortunately, the spatiotemporal nature of these pathways renders the application of conventional tools (over/under-expression of the proteins of interest, inhibitory compounds, etc.) inadequate for studying dynamic cell behavior. We seek to engineer and evaluate optogenetic analogs of cofilin, cofilin’s upstream activators (slingshot and chronophin), and cofilin’s upstream negative regulators (LIM protein kinase, the cAMP-dependent protein kinase, the p21 activated protein kinase, and rho-associated protein kinase). These species offer a means to correlate spatially-focused biochemical activity with dynamic cellular behavior including F-actin remodeling activity as well as migratory and invasive aptitudes.