Distribution of PCB Atropisomers

描述（由申请人提供）： 该指导研究科学家奖的直接目标是让Hans-Joachim Lehmler博士成功过渡到环境毒理学领域的独立研究者。 在该奖项的研究部分，Lehmler博士将测试工作假设，即手性环境污染物如PCB 84通过细胞色素P450对映体选择性代谢，导致PCB 84的一种对映体在某些组织中选择性富集。 或者，将研究血浆蛋白对PCB对映体的差异转运导致的一种PCB 84对映体的富集。具体目的是（1）确定PCB 84体外代谢的对映体选择性，（2）研究PCB 84对映体与小鼠和人血清蛋白的结合，（3）确定PCB 84对映体在雌性小鼠中的分布和处置以及对映体向胎儿和哺乳后代的转移。这一研究部分将由一个积极的职业发展计划补充，其中包括（1）生物统计学和研究道德行为的正式培训，作为职业和环境卫生部NIEHS培训补助金课程的一部分，（2）与他的导师，合作者和顾问定期会议，（3）参加小组会议和部门研讨会，（4）在多氯联苯研讨会等科学会议上介绍研究结果;（5）在同行评审的期刊上发表研究结果。 据设想，导师，合作者和顾问的多学科团队在研究以及该奖项的职业发展组成部分中发挥积极作用。长期职业目标是将Lehmler博士确立为具有独立研究地位和资金的研究者。

DESCRIPTION (provided by applicant): The immediate objective of this Mentored Research Scientist Award is to allow Dr. Hans-Joachim Lehmler to make a successful transition to an independent investigator in the field of environmental toxicology. In the research component of this award, Dr. Lehmler will test the working hypothesis is that chiral environmental contaminants such as PCB 84 are enantioselectively metabolized by cytochrome P450, resulting in a selective enrichment of one enantiomer of PCB 84 in certain tissues. Alternatively, the enrichment of one PCB 84 enantiomer resulting from differential transport of PCB enantiomers by plasma proteins will be investigated. The specific aims are (1) to determine the enantioselectivity of the in vitro metabolism of PCB 84, (2) to study the binding of both PCB 84 enantiomers to mice and human serum proteins, and (3) to determine the distribution and disposition of PCB 84 enantiomers in female mice and the transfer of the enantiomers into the fetus and suckling offspring. This research component will be complemented by a vigorous career development plan which will include (1) formal training in biostatistics and the ethical conduct of research as part of the curriculum of the NIEHS training grant in the Department of Occupational and Environmental Health, (2) regular meetings with his mentors, collaborators and consultants, (3) participation in group meetings and departmental seminars, (4) presenting results at scientific meetings such as the PCB Workshop and (5) publishing in peer reviewed journals. It is envisioned that the multidisciplinary team of mentors, collaborators and consultants plays an active role in both the research as well as the career development component of this award. The long term career goal is to establish Dr. Lehmler as an investigator with independent research status and funding.