Universiteit Leiden

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Dissertation

Quantitative live cell imaging of glucocorticoid receptor dynamics in the nucleus

In this thesis, the focus lies on studying glucocorticoid receptor dynamics in living cells with the aim of understanding how this transcription factor finds its DNA target sites to regulate transcription.

Author
Keizer, V.I.P.
Date
01 November 2018
Links
Thesis in Leiden Repository

In this thesis, the focus lies on studying glucocorticoid receptor dynamics in living cells with the aim of understanding how this transcription factor finds its DNA target sites to regulate transcription. We have uncovered several GR dynamics states and obtained insight into how the receptor finds its target, which includes repetitive switching between states. In addition, we have made a quantitative description of the static distribution of this transcription factor in the nucleus and compared this to a homologous transcription factor, the estrogen receptor. We have advanced the experimental techniques used to answer this question through development of novel analysis tools. These include a method to correct analytically for observation bias of different diffusion modes in a two dimensional plane. Furthermore, we have investigate the use of an alternative labeling method, namely the gold nanorod. To this end, the behavior and functionalization of gold nanorods was characterized in live cells.

 

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