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Admin Supplement: Identifying the ABCs of xenobiotic metabolism in protecting the germ line lineage

管理补充：识别外源代谢在保护种系谱系中的 ABC

基本信息

批准号：
10478396
负责人：
Catherine Schrankel
金额：
$ 4.78万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-12-01 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10478396
关键词：
ABCB1 gene ABCC1 gene ATP-Binding Cassette Transporters Adult Affect Animal Model Apoptosis Binding Biological Assay Biological Models CRISPR/Cas technology Carrier Proteins Cell Line Cell membrane Cells Data Development Developmental Toxicant Dose Drug Metabolic Detoxication Elderly Embryo Environment Environmental Exposure Environmental Pollutants Exposure to Family Functional disorder Genetic Germ Cells Germ Lines Glutathione Health Homeostasis Human Human Cell Line Infertility Knock-out Lead Ligands Liquid substance Measurement Membrane Transport Proteins Metabolism Modeling Multi-Drug Resistance Oxidation-Reduction Oxidative Stress Pathway interactions Pharmaceutical Preparations Phase Population Predisposition Proteins Research Role Sea Urchins Signal Transduction Signaling Molecule Specific qualifier value Structure of primordial sex cell Sulfhydryl Compounds System Testing Toxicant exposure Toxin Umbilical Blood Umbilical Cord Blood Work Xenobiotic Metabolism Xenobiotics bisphenol A blastomere structure cell motility dosage early life exposure egg environmental chemical experimental study human embryonic stem cell human model imaging approach in utero in vivo lipid metabolism live cell imaging migration next generation oxidation pollutant prenatal prenatal exposure protein function reproductive response sperm cell stem cell model toxicant

项目摘要

Contact PD/PI: Schrankel, Catherine PROJECT SUMMARY/ABSTRACT This project explores the cellular protection systems available to the primordial germ line—the embryonic precursors to egg and sperm. The research is centered on the developmental and protective functions of a class of multi-drug resistance ABC transporters that actively efflux toxins, reactive metabolites, and signaling molecules from the cell. It will use two model systems—the sea urchin embryo and a human cell line—to identify these functions in the development and protection of primordial germ cells (PGCs). PGCs have not been characterized in this context before, despite the ubiquitous presence of “low-dose” pollutants and drugs in the environment, umbilical cord blood and maternal fluids. Modeling the threshold of protective mechanisms in PGCs is crucial for predicting and mitigating early life exposures, in order to help define safe dosage levels and mitigate infertility issues that may arise in utero. Project Summary/Abstract

联系PD/PI：Schrankel，Catherine 项目总结/摘要这个项目探讨了原始生殖系（胚胎）的细胞保护系统。卵子和精子的前体。这项研究的重点是一种发育和保护功能，一类主动外排毒素、反应性代谢物和信号传导的多药耐药ABC转运蛋白细胞中的分子。它将使用两个模型系统-海胆胚胎和人类细胞系-来确定这些功能的发展和保护原始生殖细胞（PGCs）。PGCs没有尽管“低剂量”污染物和药物无处不在，在环境中，脐带血和母亲的体液中。保护阈值建模 PGC中的机制对于预测和减轻早期生命暴露至关重要，以帮助定义安全的剂量水平和减轻不孕症的问题，可能会出现在子宫内。项目总结/摘要