Circadian clocks allow organisms to adapt biochemical and physiological processes to their environment in rhythms entrained by the solar day. There is intriguing evidence that the toxicological response to a number of xenobiotic compounds varies with time of day in many species, including humans. From these reports, it can be inferred that organisms may protect themselves from environmental toxins by increasing molecular defenses when daily exposure is most expected. We will test this novel hypothesis by monitoring mortality of Drosophila melanogaster exposed to pyrethroids at different times of day. Preliminary microarray data have revealed putative rhythmic expression patterns in genes responsible for detoxifying pyrethroids. We will characterize these patterns and examine the involvement of these genes in rhythmic susceptibility to pyrethroids. Using the tools of systems biology, existing microarray data, and our own results, we will construct a model of the convergence of circadian and toxicological networks in order to highlight common regulatory mechanisms. Humans are inevitably exposed to pyrethroids and other pesticides, and this interdisciplinary investigation is likely to lead to novel strategies protective of human health. ? ? ?
|Beaver, Laura Michelle; Hooven, Louisa Ada; Butcher, Shawn Michael et al. (2010) Circadian clock regulates response to pesticides in Drosophila via conserved Pdp1 pathway. Toxicol Sci 115:513-20|
|Hooven, Louisa A; Sherman, Katherine A; Butcher, Shawn et al. (2009) Does the clock make the poison? Circadian variation in response to pesticides. PLoS One 4:e6469|