It takes the average reader 4 hours and 12 minutes to read Mathematical Modeling of NF-κB and p53 Signaling in the DNA Damage Response by Fabian Konrath
Assuming a reading speed of 250 words per minute. Learn more
Cells are permanently challenged by DNA damage which can be induced by environmental factors such as UV irradiation or intracellular factors like reactive oxygen species. As damaged DNA can lead to malignant transformations, a complex signaling network termed DNA damage response is activated upon detection of DNA lesions and allows to maintain genomic integrity. The two transcription factors NF-κB and p53 regulate cell fate decisions upon genotoxic stress and therefore play crucial roles in the DNA damage response. To investigate the regulation of NF-κB activity, a mathematical model of coupled ordinary differential equations was developed and analyzed. The model describes DNA damage-induced activation of NF-$&appa;B and quantitatively reproduces multiple experimental data sets. Analyzing the time-resolved regulation of NF-κB revealed regulatory mechanisms of DNA damage-dependent NF-κB signaling and allowed the evaluation of drug targets inhibiting NF-κB activity. Further, the interplay of NF-κB and p53 signaling was investigated by developing a mathematical modeling framework to systematically identify interfaces between the NF-κB and p53 network. NF-κB signaling was perturbed and the resulting changes in single cell dynamics of p53 upon genotoxic stress were captured. By fitting a pool of subpopulation-specific ordinary differential equation models to the single cell data, one of the first quantitative p53 models reproducing the heterogeneous dynamics of p53 was developed. Based on the observed changes in p53 dynamics, the results of the modeling framework indicate that NF-κB signaling interferes with the activation and degradation of p53 as well as the degradation of its inhibitor Mdm2. Taken together, the results in this work give new insights into the regulation of genotoxic NF-κB and p53 signaling and highlight the complexity of their crosstalk.
Mathematical Modeling of NF-κB and p53 Signaling in the DNA Damage Response by Fabian Konrath is 251 pages long, and a total of 63,001 words.
This makes it 85% the length of the average book. It also has 77% more words than the average book.
The average oral reading speed is 183 words per minute. This means it takes 5 hours and 44 minutes to read Mathematical Modeling of NF-κB and p53 Signaling in the DNA Damage Response aloud.
Mathematical Modeling of NF-κB and p53 Signaling in the DNA Damage Response is suitable for students ages 12 and up.
Note that there may be other factors that effect this rating besides length that are not factored in on this page. This may include things like complex language or sensitive topics not suitable for students of certain ages.
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