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Extramural Research

Grantee Research Project Results

NCER Grantee Research Project Results

Molecular Mechanisms of Methoprene Resistance in Anopheles gambiae and Anopheles gambiae and Their Relationship to the Mammalian Aryl Hydrocarbon Response Cascade

EPA Grant Number: FP916385
Title: Molecular Mechanisms of Methoprene Resistance in Anopheles gambiae and Anopheles gambiae and Their Relationship to the Mammalian Aryl Hydrocarbon Response Cascade
Investigators: McDonnell, Cynthia M.
Institution: University of Illinois at Urbana-Champaign
EPA Project Officer: Jones, Brandon
Project Period: January 1, 2004 through December 31, 2006
Project Amount: $107,161
RFA: STAR Graduate Fellowships (2004)
Research Category: Academic Fellowships , Biology/Life Sciences , Fellowship - Entomology

Description:

Objective:

The objective of this research is to determine the relationship between the molecular mechanisms that confer resistance to the insect hormone analog, methoprene, in Anopheles gambiae and Anopheles gambiae , and the mechanisms of endocrine disruption in vertebrates by environmental toxins (i.e., dioxin, PCBs, and DDT), with a focus on xenobiotic-controlled regulation of cytochrome P450 genes.

Approach:

I have proposed three strategies to investigate this objective:

(1) Cytochrome P450s in D. melanogaster and A. gambiae that are regulated by methoprene and endocrine-disrupting environmental toxins will be identified using RT-PCR.

(2) Putative cis- and trans-regulatory elements from multiple characterized regulatory pathways will be tested for their participation in regulation of cytochrome P450s by methoprene and environmental toxins using transfection assays in insect cell lines.

(3) The utility of regulated cytochrome P450s and associated regulatory proteins as molecular markers of methoprene-resistance and susceptibility will be tested by surveying field populations of mosquitoes and nontarget invertebrates that are both resistant and susceptible to methoprene.

Supplemental Keywords:

fellowship, methoprene, Anopheles gambiae , Drosophila melanogaster, environmental toxins, cytochrome P450 genes, RT-PCR, aryl hydrocarbon response, molecular markers, biomarkers,, RFA, Health, Scientific Discipline, POLLUTANTS/TOXICS, Entomology, Environmental Chemistry, Chemicals, Endocrine Disruptors - Environmental Exposure & Risk, endocrine disruptors, Ecology and Ecosystems, Endocrine Disruptors - Human Health, bioindicator, biomarkers, molecular mechanisms, cytotoxic, bioavailability, EDCs, exposure studies, PCBs, molecular markers, insect hormone, animal models, DDT, cytochrome P450 genes

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.

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