Systems-level analysis of the regulation and function of p53 dynamics

目的：在这个项目中，我们将使用计算和实验技术相结合的方法来确定p53动力学在重要细胞应激的调节中的作用。为了测量下游途径的动态，我们将利用下面描述的一套互补方法来测定癌变和非转化细胞系统中的p53活性。我们将使用化学和遗传扰动来改变p53动力学，并确定对p53靶基因表达和细胞命运的影响。使用计算模型，我们将把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途径行为。通过允许我们研究在小规模相互作用水平上不明显的新特性，这种类型的方法将为操纵生物电路功能提供新策略，并产生对抗p53动力学失调的癌症的新方法。由于Batchelor博士的离职，该项目的进展于2020财年结束

PURPOSE: In this project, we will use a combination of computational and experimental techniques to identify the role of p53 dynamics in the regulation of important cellular stress stresses. To measure the dynamics of downstream pathways, we will make use of a suite of complementary approaches described below to assay p53 activity in both cancerous and non-transformed cellular systems. We will use chemical and genetic perturbations to alter p53 dynamics and determine the effect on p53 target gene expression and cell fate. Using computational modeling, we will integrate these data with measurements of cellular outcomes to predict pathway behavior in response to specific perturbations. 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 biological circuit functions, as well as generate new ways to combat cancers in which p53 dynamics are dysregulated. Progress on this project was concluded in FY20 due to the departure of Dr. Batchelor