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Toxins are a fact of life. Not only do we eat potentially harmful compounds, but the biochemistry of our cells is also constantly producing molecules that are potential hazards to our cellular health. However, since most of us seem to be reasonably resistant to this constant internal chemical warfare, our cells must either be very resilient or wisely taking out the trash. It turns out that the later of the two is the more correct answer. In the last several years, the combined efforts of many biologists have revealed that proteins in the Nuclear Receptor (NR) Superfamily, other members of which are the receptors for many hormones such as estrogen and thyroid hormone, are responsible for this toxic resistance. One of the NRs, called PXR, has been termed the “xenobiotic sensing” receptor for its ability to activate toxin resistance pathways when the offending compounds show up in our hepatic (liver) and intestinal cells. (Xenobiotics are chemicals not normally found in living systems such as pesticides or drugs.) Xenobiotics and toxic molecules produced by our bodies bind to and activate PXR causing it to up-regulate the production of many kinds of detoxification enzymes. This process is obviously important, after all, I plan to keep on eating those toxic molecules (they’re pretty hard to avoid). Therefore, I’ve chosen to try and discover the identity of both the genes that are regulated by xenobiotic sensing NRs and the molecules that activate the whole process. However, since very few people are willing to subject themselves to toxic cocktails and liver biopsies, I have chosen to study the process of NR mediated regulation of the detoxification network in a small, free living, soil nematode called Caenorhabditis elegans. Yep, it’s the worm at the top of the page.