K.C. Donnelly Externship - Promotion of Translational/Transdisciplinary Efforts in Graduate and Post-Doctoral Research - Dasgupta

K.C.

• 批准号: 10381316
• 负责人: Robyn L Tanguay
• 金额: $ 1.38万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-16 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10381316
• 关键词: Active Learning; Adult; Area; Aromatic Polycyclic Hydrocarbons; Aryl Hydrocarbon Receptor; Atlases; Automobile Driving; Behavioral; Benzo(a)pyrene; Bioinformatics; Biology; Brain; Child; Cognitive; Complex; Development; Embryo; Environmental Pollution; Exposure to; Fertilization; Modeling; Nervous System Physiology; Neurotoxins; Organ; Pattern; Postdoctoral Fellow; Research; Role; Signal Recognition Particle; Superfund; Technology; Toxic effect; Training; Water; Work; Zebrafish; cell type; chemical group; deep sequencing; externship; neurodevelopmental effect; neurotoxic; prenatal exposure; programs; single cell sequencing; superfund site; transcriptomics

PROJECT DESCRIPTION (ABSTRACT) Polycyclic aromatic hydrocarbons (PAHs)- a group of environmental contaminants commonly found in Superfund sites- have been well-established as developmental neurotoxicants. Prenatal exposure to PAHs has been associated with decreased cognitive status among children. As a part of the OSU SRP, our lab uses the zebrafish model to study the mechanisms of PAH toxicity, including the role of aryl hydrocarbon receptor. Work from our group has shown that in addition to neurodevelopmental effects, developmental exposures to some PAHs, such as benzo-a-pyrene (BaP), result in cognitive and behavioral deficits in adults; however, the mechanisms are still not clear. The brain is a complex organ with specific areas and cell-types regulating various nervous system functions, including behavioral patterns. Single cell sequencing is an ideal technology that can identify cell type-specific transcriptomic atlas of an organ using deep sequencing and established transcriptomic markers. I will achieve training in this technology from Dr. Bruce Danton and Dr. Britton Goodale at the Dartmouth Superfund Center to study changes in the transcriptomic atlas of zebrafish brain that drives persistent neurotoxic effects of PAHs. Briefly, I will expose zebrafish embryos 4 µM BaP- a concentration that has been shown to induce adult behavioral deficits- from 6 to 120 h post fertilization (hpf), grow them out in clean water, dissect their brains and perform single cell sequencing and bioinformatic analyses through hands-on training in Dartmouth. This project will result in a better understanding of the biology driving PAH- induced long-term behavioral disruptions. Through experiential learning, I will add this state-of-the-art technology to my research portfolio and can apply this to diverse groups of chemicals when I transition into my independent research program.

项目说明（摘要） 多环芳烃（PAHs）-一组环境污染物， 超级基金网站-已被公认为发育神经毒物。产前暴露于 多环芳烃与儿童认知状态下降有关。作为OSU SRP的一部分， 我们实验室使用斑马鱼模型来研究PAH毒性的机制，包括芳基的作用， 烃受体我们小组的工作表明，除了神经发育的影响， 发育期暴露于某些多环芳烃，如苯并-a-芘（BaP），会导致认知和 成人行为缺陷;然而，其机制仍不清楚。大脑是一个复杂的器官 具有调节各种神经系统功能的特定区域和细胞类型，包括行为 模式.单细胞测序是一种理想的技术，可以鉴定细胞类型特异性转录组， 使用深度测序和已建立的转录组学标记来绘制器官图谱。我将实现训练 来自达特茅斯超级基金中心的布鲁斯丹顿博士和布里顿古德尔博士 研究斑马鱼大脑转录组图谱的变化， 的PAH。简单地说，我将暴露斑马鱼胚胎4 μM BaP-一个浓度已被证明， 诱导成虫行为缺陷-从受精后6至120小时（HPF），使它们在干净水中生长， 解剖他们的大脑，通过动手操作进行单细胞测序和生物信息学分析， 在达特茅斯受训该项目将导致更好地了解生物驱动PAH- 导致长期的行为紊乱通过体验式学习，我将把这种最先进的 技术，我的研究组合，并可以将其应用到不同的化学品组，当我过渡 我的独立研究项目