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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32ES014994-03
Application #
7476418
Study Section
Special Emphasis Panel (ZRG1-F02A-H (20))
Program Officer
Humble, Michael C
Project Start
2006-08-15
Project End
2009-08-14
Budget Start
2008-08-15
Budget End
2009-08-14
Support Year
3
Fiscal Year
2008
Total Cost
$52,048
Indirect Cost
Name
Oregon State University
Department
Zoology
Type
Schools of Arts and Sciences
DUNS #
053599908
City
Corvallis
State
OR
Country
United States
Zip Code
97339
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