University of Twente Student Theses


Investigating the kinetics of the B-cell receptor signaling network in a dynamic environment

Kiffen, Bas (2023) Investigating the kinetics of the B-cell receptor signaling network in a dynamic environment.

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Abstract:Signal transduction is an important mechanism employed by cells to sense and respond to changes in their microenvironment. These changes are translated into a functional response by signaling networks consisting of receptors, kinases, phosphatases, transcription factors, and other molecules. Improving our understanding of these cellular signaling networks helps with identifying disease-associated signaling components and the development of new drug treatments. The BCR signaling network is an important network that is engaged in B-cell activation, development, proliferation, differentiation, and apoptosis. Malignant B-cells have elevated levels of ROS such as H2O2, due to their high metabolic activity. Upregulation of antioxidants in malignant B-cells brings their intrinsic ROS to a level that promotes chronic proliferation and differentiation, resulting in a poor prognosis. While the response of the BCR signaling network to H2O2 has been studied extensively, it has only been studied in response to step-wise increases of H2O2, which fails to replicate the dynamic in vivo environment. In this work, the differences in BCR signaling response of the DLBCL cell line HBL1 in response to static inputs and dynamic inputs of H2O2 have been compared. Our results show the contrast between activation patterns of the BCR signaling proteins CD79a, PLCγ2, and Syk in HBL1 cells stimulated with H2O2 step increases and H2O2 gradients. We demonstrate that, compared to step increases to the same concentration H2O2, gradients induce a signaling response that is stronger, weaker, or not not present at all, depending on the cell density, end concentration of H2O2, and flow rate.
Item Type:Essay (Master)
Faculty:TNW: Science and Technology
Subject:02 science and culture in general, 42 biology
Programme:Biomedical Engineering MSc (66226)
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