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

项目说明(摘要) 多环芳烃(PAHs)--一组常见于 超级基金网站-已被公认为发育神经毒剂。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多环芳烃的毒性机制，包括芳基的作用。 碳氢化合物受体。我们团队的研究表明，除了对神经发育的影响外， 发育过程中暴露于某些多环芳烃，如苯并-α-芘(BaP)，会导致认知和 成人的行为缺陷；然而，其机制仍不清楚。大脑是一个复杂的器官 具有特定的区域和细胞类型，调节各种神经系统功能，包括行为 模式。单细胞测序是一种理想的技术，可以识别特定细胞类型的转录 使用深度测序和已建立的转录标记的器官图谱。我会完成训练的 在达特茅斯超级基金中心的布鲁斯·丹顿博士和布里顿·古代尔博士的这项技术中 研究驱动持续神经毒性效应的斑马鱼脑转录图谱的变化 多环芳烃的含量。简单地说，我将暴露斑马鱼胚胎4微米Bap-这个浓度已经被证明 诱导成人行为缺陷--受精后6至120小时(HPF)，在干净的水中培养它们， 解剖他们的大脑，通过动手进行单细胞测序和生物信息学分析 在达特茅斯接受训练。这一项目将有助于更好地理解推动PAH的生物学机制-- 导致了长期的行为中断。通过体验式学习，我将添加这一最先进的 技术应用到我的研究组合中，并可以在我过渡时将其应用于不同类别的化学品 加入我的独立研究项目。

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.