Modeling Genetic Regulation in the NF-kB Signaling System – Niels Bohr Institute - University of Copenhagen

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Niels Bohr Institute > Calendar > 2007 > Thesis by Benedicte Me...

Modeling Genetic Regulation in the NF-kB Signaling System

NF-kB is a protein present in human cells and is involved in many processes such as immune response, inflammation, cellular growth, survival and apoptosis. Additionally, it is active in a large number of diseases, including cancer, heart diseases and asthma.

The NF-kB signaling system is known to transcribe more than 150 genes, but how the gene specificity is obtained remains unclear. Experiments have revealed sustained oscillations in the nuclear concentration of the transcription factor in double knockout cells, where the wild-type response is damped. The activity of the transcription factor NF-kB is controlled by the three inhibitor proteins IkBa, IkBb and IkBe.

A model of three, coupled differential equations have already been developed to capture the overall oscillatory dynamics of the transcription factor and the inhibitor protein IkBa. Later experimental work has revealed that two additional inhibitor proteins, IkBe and IkBb, provides a negative feedback which is essential in the regulation of NF-kB. In this thesis, I aim to include the additional inhibitor proteins in the simplified model, providing the delayed and dampening regulation of NF-kB, and thereby making the model closer to the wild-type system.

The output of the model has been compared with the behaviour known from experiments, and it is found that the model exhibits the experimentally observed features.

 

Supervisor: Mogens Høgh Jensen