Organochlorine pesticide effects on neurotransmitter signaling

描述(由申请人提供) 这位目前在佛罗里达大学(UF)从事博士后研究的候选人正在研究蛋白质对环境污染物的反应，这是对他的神经基因组学和神经生理学背景的极好补充。这位候选人之所以选择密歇根大学进行博士后研究和指导研究，是因为密歇根大学拥有完善的研究中心(ICBR)，致力于基因组和蛋白质组分析，环境和人类毒理学中心拥有强大的毒理基因组研究计划。他的长期研究目标是开发必要的工具，研究环境污染物对神经内分泌功能的影响以及对脊椎动物HPG轴的影响。这项建议调查有机氯农药(OCR)、狄氏剂和α-硫丹对神经内分泌功能和生殖调节的影响。这些OCR在环境中持续存在，并继续成为野生动物和人类健康的关注点。接触OCR的主要目标是神经递质GABA(GABA-A受体)和多巴胺(DA)。在指导阶段，候选人的直接目标是继续进行蛋白质组学方面的培训。这是一个不断发展的领域，将补充他在基因组学方面的强大背景，以了解神经生理学背后的分子事件。他还将采用生物信息学方法来整合生理、基因组和蛋白质组数据。在独立研究阶段，候选人将研究OCR对GABA和DA代谢酶丰度和活性的影响，因为有证据表明，随着神经退行性疾病，酶活性会改变。他将使用大脑中的形态(细胞凋亡)和生化终点(神经递质代谢和水平)、垂体(促性腺激素合成)和性腺(类固醇生产)作为基因组(微阵列)和蛋白质组(ITRAQ)的表型锚，以更好地了解OCRs如何影响大脑和生殖控制。这种系统生物学方法可以用于研究环境中的其他神经活性化合物，以评估对环境和人类健康的风险。

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.