Organochlorine pesticide effects on neurotransmitter signaling

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DESCRIPTION (provided by applicant) The candidate current postdoctoral research at the University of Florida (UF) is studying the response of proteins to environmental contaminants and is an excellent compliment to his neurogenomics and neurophysiology background. The candidate chose UF for his postdoctoral research and mentored research because UF has a well established research center (ICBR) dedicated to genomic and proteomic analysis and the Center for Environmental and Human Toxicology has a strong toxicogenomic research program. His long term research goals are to develop the tools needed to study the effects of environmental contaminants on neuroendocrine function and impacts on the vertebrate HPG axis. This proposal investigates the effects of organochloride pesticides (OCRs) dieldrin and alpha-endosulfan on neuroendocrine function and the regulation of reproduction. These OCRs are persistent in the environment and continue to be a concern for wildlife and human health. Major targets of OCR exposure are the neurotransmitters GABA (GABA-A receptors) and dopamine (DA). During the mentored phase, the candidate's immediate goals will be continued training in proteomics. This is a growing field that will compliment his strong background in genomics to understand molecular events underlying neurophysiology. He will also adapt bioinformatic approaches to integrate physiological, genomic, and proteomic data. In the independent research phase, the candidate will study the effects of OCRs on GABA and DA metabolizing enzyme abundance and activity since there is evidence that enzyme activity is altered with neurodegenerative diseases. He will use morphological (apoptosis) and biochemical endpoints in the brain (neurotransmitter metabolism and levels), pituitary (gonadotropin synthesis), and gonad (steroid production) as phenotypic anchors for genomic (microarray) and proteomic (iTRAQ) to better understand how OCRs impact the brain and the control of reproduction. This systems biology approach can be utilized to study other neuroactive compounds in the environment to assess risks to environmental and human health.