Spatiotemporal Control of Migratory Cellular Behavior

迁移细胞行为的时空控制

• 批准号: 9900075
• 负责人: DAVID S. LAWRENCE
• 金额: $ 34.02万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-15 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9900075
• 关键词: Adenylate Cyclase; Apoptosis; Aptitude; Attention; Behavior; Biochemical; Biochemical Pathway; Cells; Chemotaxis; Cyclic AMP-Dependent Protein Kinases; Cytoskeleton; Descriptor; Development; Diffuse; Disease; Drug Delivery Systems; Elements; Engineering; Enzyme Activators; Epithelial; Epithelium; F-Actin; Funding; Genetic Engineering; Glioblastoma; Grant; Infiltration; Light; Mediating; Mediator of activation protein; Mesenchymal; Modeling; Nature; Neurologic; Organism; Pathway interactions; Phenotype; Protein Engineering; Protein Kinase; Protein phosphatase; Proteins; PubMed; Regulation; Reporter; Research; Series; Signal Transduction; Site; United States National Institutes of Health; Variant; analog; cancer cell; cell behavior; cell motility; cell type; cofilin; design; inhibitor/antagonist; interest; member; migration; nervous system disorder; optogenetics; programs; protein expression; rho; spatiotemporal; therapeutic target; tool; tumor

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.

项目概要 人们对确定促进肿瘤脑内浸润的生化途径产生了浓厚的兴趣，因为 不幸的是，这些途径的成员作为潜在的治疗靶点。 这些途径使得常规工具的应用（感兴趣的蛋白质的过度/不足表达， 抑制化合物等）不足以研究动态细胞行为。我们寻求设计和评估。 cofilin 的光遗传学类似物、cofilin 的上游激活剂（弹弓和 chronophin）以及 cofilin 的上游 负调节因子（LIM 蛋白激酶、cAMP 依赖性蛋白激酶、p21 激活蛋白激酶、 和 rho 相关蛋白激酶）这些物种提供了一种关联空间聚焦生化的方法。 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 资质。