PXR, Ligand, and Co-Activator Interactions Characterized by TIRFM (2012)

Undergraduate: Valerie Hansen

Faculty Advisor: Nancy Thompson
Department: Chemistry

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PXR, a nuclear receptor, plays a role in removing potentially toxic compounds from the body by enhancing the expression of enzymes that degrade toxins. Thus, understanding PXR is important for human health, but the mechanism by which PXR functions is not yet understood. Based on the mechanisms of other nuclear receptors, it was thought that the presence of a ligand should increase PXR’s affinity for a co-activator known as SRC-1. Using total internal reflection fluorescence microscopy (TIRFM), I aimed to test this hypothesis in order to learn more about how PXR functions and how it impacts the removal of potential toxins from the body.

First, I conducted a series of “control” experiments that confirmed the experimental system functioned as expected and that all of the assumptions present in the model were correct. Secondly, I conducted experiments to determine if the presence of a ligand (specifically, Rifampicin) increases the affinity of PXR for the SRC-1 co-activator.

The results of these control experiments confirmed the assumptions of the experimental system, and the later experiments showed that the presence of the ligand Rifampicin did not increase the affinity of PXR for the SRC-1 co-activator. Further experiments with different ligands and different co-activators may better elucidate the PXR mechanism and how it helps to remove toxins from the body.