Systems-level analysis of the regulation and function of c-Myc

c-Myc 调控和功能的系统级分析

• 批准号: 8763560
• 负责人: Eric Batchelor
• 金额: $ 14.8万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8763560
• 关键词: Address; Affect; Alleles; Behavior; CCR; Cell Proliferation Regulation; Cell physiology; Cells; Collaborations; Computer Simulation; Cues; Data; Embryo; Fibroblasts; Fluorescence Microscopy; Genes; Goals; Green Fluorescent Proteins; Growth; Individual; Life; Malignant Neoplasms; Masks; Measurement; Measures; Mus; Outcome; Pathway interactions; Play; Population; Property; Proto-Oncogenes; Regulation; Role; Signal Transduction; Stimulus; System; Techniques; Time; Work; c-myc Genes; chemical genetics; combat; insight; novel strategies; novel therapeutics; response; transcription factor

PURPOSE: In this project, we will use a combination of computational and experimental techniques to characterize c-Myc dynamics in a variety of cell systems in response to c-Myc activating cues. By allowing us to study emergent properties that are not evident at the level of smaller-scale interactions, this type of approach will provide novel strategies for manipulating circuit functions, as well as new ways to combat cancers in which c-Myc dynamics are deregulated. MATERIALS AND METHODS: To measure the dynamics of circuit components, we will primarily use long-term time-lapse fluorescence microscopy of living individual cells in which c-Myc has been fluorescently tagged. We will use chemical and genetic perturbations to alter c-Myc dynamics and determine the effects on cellular functions. Using computational modeling, we will integrate these data with measurements of cellular outcomes to predict pathway behavior in response to specific perturbations. PROGRESS IN FY2013: We have made use of mouse embryonic fibroblasts in which the gene encoding the green fluorescent protein GFP has been inserted into the endogenous loci of both c-Myc alleles. Using these cells, we have begun to characterize the dynamics of c-Myc in response to various stimuli. This work is being performed in collaboration with David Levens (LP/CCR).

目的：在这个项目中，我们将结合使用计算和实验技术来表征各种细胞系统中响应 c-Myc 激活信号的 c-Myc 动力学。通过让我们研究在小规模相互作用水平上不明显的新兴特性，这种方法将为操纵电路功能提供新策略，以及对抗 c-Myc 动力学失调的癌症的新方法。材料和方法：为了测量电路元件的动态，我们将主要使用活体单个细胞的长期延时荧光显微镜，其中 c-Myc 已被荧光标记。我们将利用化学和遗传扰动来改变 c-Myc 动力学并确定对细胞功能的影响。使用计算模型，我们将这些数据与细胞结果的测量相结合，以预测响应特定扰动的通路行为。 2013 财年的进展：我们利用了小鼠胚胎成纤维细胞，其中编码绿色荧光蛋白 GFP 的基因已插入到两个 c-Myc 等位基因的内源基因座中。使用这些细胞，我们已经开始表征 c-Myc 响应各种刺激的动态。这项工作是与 David Levens (LP/CCR) 合作进行的。