Distribution of PCB Atropisomers

描述(由申请人提供)： 这一指导研究科学家奖的直接目标是让汉斯-约阿希姆·莱姆勒博士成功地过渡到环境毒理学领域的独立研究人员。在该奖项的研究部分，Lehmler博士将检验工作假设，即手性环境污染物，如多氯联苯84，被细胞色素P450对映体选择性代谢，导致多氯联苯84的一个对映体在某些组织中选择性浓缩。或者，将研究由于血浆蛋白对多氯联苯对映体的不同转运而导致的对多氯联苯84对映体的浓缩。其具体目的是(1)测定PCB84体外代谢的对映体选择性；(2)研究PCB84对映体与小鼠和人血清蛋白的结合；(3)测定PCB84对映体在雌性小鼠体内的分布和分布，以及对映体在胎儿和哺乳后代体内的转移。这一研究部分将得到一个强有力的职业发展计划的补充，该计划将包括：(1)作为职业和环境卫生部门NIEHS培训补助金课程的一部分，在生物统计学和研究道德方面进行正式培训，(2)与他的导师、合作者和顾问定期会晤，(3)参加小组会议和部门研讨会，(4)在多氯联苯讲习班等科学会议上介绍成果，以及(5)在同行评议的期刊上发表文章。预计由导师、合作者和顾问组成的多学科团队将在该奖项的研究和职业发展部分发挥积极作用。长期的职业目标是让莱姆勒博士成为一名拥有独立研究地位和资金的研究员。

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.