P53 dynamics: single-cell imaging data analysis and modeling

Abstract

The p53 protein plays a central role in controlling the fate of cancer cells. At moderate levels of DNA damage, the concentration of the phosphorylated form of p53 undergoes temporal oscillation with a period of a few hours. In Dr. Shi’s lab, single-cell measurements were carried out using the p53-YFP fusion proteins and time-lapse fluorescence microscopy. We report here a detailed study of the image data. From the time series of the p53 concentration in individual cells, we deduce the amplitude and period of the oscillation. The pulse-to-pulse and cell-to-cell variability of the oscillation is characterized. We then carry out a computational study of a mathematical model that involves a negative feedback loop between p53 and Mdm2 proteins. We have determined the phase diagram of the model, and studied the sensitivity of the properties of the oscillating state against the model parameters. Although only p53 concentration is measured in the experiment, we show that careful analysis of the pulse shape can nevertheless yield valuable information on the underlying molecular processes, and shed light on the possible origin of the observed cellto- cell variations.

Date of Award	1 Sept 2014
Original language	English
Supervisor	Lei Han TANG (Supervisor)